Artículos de revistas sobre el tema "Focal cerebral ischemia"
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1
Hua, Y., G. Xi, G. M. de Courten-Myers, K. R. Wagner y R. E. Myers. "FOCAL CEREBRAL ISCHEMIA". Journal of Neuropathology and Experimental Neurology 55, n.º 5 (mayo de 1996): 663. http://dx.doi.org/10.1097/00005072-199605000-00240.
2
Kanazawa, Masato, Tetsuya Takahashi, Masanori Ishikawa, Osamu Onodera, Takayoshi Shimohata y Gregory J. del Zoppo. "Angiogenesis in the ischemic core: A potential treatment target?" Journal of Cerebral Blood Flow & Metabolism 39, n.º 5 (6 de marzo de 2019): 753–69. http://dx.doi.org/10.1177/0271678x19834158.
Resumen
The ischemic penumbra is both a concept in understanding the evolution of cerebral tissue injury outcome of focal ischemia and a potential therapeutic target for ischemic stroke. In this review, we examine the evidence that angiogenesis can contribute to beneficial outcomes following focal ischemia in model systems. Several studies have shown that, following cerebral ischemia, endothelial proliferation and subsequent angiogenesis can be detected beginning four days after cerebral ischemia in the border of the ischemic core, or in the ischemic periphery, in rodent and non-human primate models, although initial signals appear within hours of ischemia onset. Components of the neurovascular unit, its participation in new vessel formation, and the nature of the core and penumbra responses to experimental focal cerebral ischemia, are considered here. The potential co-localization of vascular remodeling and axonal outgrowth following focal cerebral ischemia based on the definition of tissue remodeling and the processes that follow ischemic stroke are also considered. The region of angiogenesis in the ischemic core and its surrounding tissue (ischemic periphery) may be a novel target for treatment. We summarize issues that are relevant to model studies of focal cerebral ischemia looking ahead to potential treatments.
3
Kinuta, Yuji, Haruhiko Kikuchi, Masatsune Ishikawa, Mieko Kimura y Yoshinori Itokawa. "Lipid peroxidation in focal cerebral ischemia". Journal of Neurosurgery 71, n.º 3 (septiembre de 1989): 421–29. http://dx.doi.org/10.3171/jns.1989.71.3.0421.
Resumen
✓ To verify whether lipid peroxidation is associated with focal cerebral ischemia, a unilateral middle cerebral artery occlusion was carried out in rats. The concentrations of various endogenous antioxidants in the ischemic center were measured, including α-tocopherol and ubiquinones as lipid-soluble antioxidants and ascorbate as a water-soluble antioxidant. At 30 minutes after ischemia, α-tocopherol decreased to 79% of baseline, reduced ubiquinone-9 to 73%, ubiquinone-10 to 66%, and reduced ascorbate to 76%. Six hours after ischemia, α-tocopherol decreased to 63% and reached a plateau, whereas reduced ubiquinones and reduced ascorbate declined further to 16% and 10%, respectively, 12 hours after ischemia and then reached plateau levels. These results suggest functional and durational differences between antioxidants and lipid peroxidation in this ischemic model. Although the reciprocal increase in oxidized ubiquinones during ischemia was not observed, that of oxidized ascorbate was noted. The complementary antioxidant system between cytoplasmic and membranous components, the combination α-tocopherol/ascorbate, was estimated from the calculated consumption ratio of these antioxidants on the basis that the loss of these reduced antioxidants is due to neutralization of free radicals. This system is suggested to play an important role in the early ischemic period. Urate also increased during ischemia. The possible involvement of the xanthine-xanthine oxidase system in initiating free radical reactions in cerebral ischemia is also discussed.
4
Pettigrew, L. Creed, Mary L. Holtz, Susan D. Craddock, Stephen L. Minger, Nathan Hall y James W. Geddes. "Microtubular Proteolysis in Focal Cerebral Ischemia". Journal of Cerebral Blood Flow & Metabolism 16, n.º 6 (noviembre de 1996): 1189–202. http://dx.doi.org/10.1097/00004647-199611000-00013.
Resumen
Calpain, a neutral protease activated by calcium, may promote microtubular proteolysis in ischemic brain. We tested this hypothesis in an animal model of focal cerebral ischemia without reperfusion. The earliest sign of tissue injury was observed after no more than 15 min of ischemia, with coiling of apical dendrites immunolabeled to show microtubule-associated protein 2 (MAP2). After 6 h of ischemia, MAP2 immunoreactivity was markedly diminished in the infarct zone. Quantitative Western analysis demonstrated that MAP2 was almost unmeasurable after 24 h of ischemia. An increase in calpain activity, shown by an antibody recognizing calpain-cleaved spectrin fragments, paralleled the loss of MAP2 immunostaining. Double-labeled immunofluorescent studies showed that intraneuronal calpain activity preceded evidence of MAP2 proteolysis. Perikaryal immunolabeling of τ protein became increasingly prominent between 1 and 6 h in neurons located within the transition zone between ischemic and unaffected tissue. Western blot experiments confirmed that dephosphorylation of τ protein occurred during 24 h of ischemia, but was not associated with significant loss of τ antigen. We conclude that focal cerebral ischemia is associated with early microtubular proteolysis caused by calpain.
5
Han, Xue Mei, Hong Tao Wei y Song Yan Liu. "Involvement of Erythropoietin Expression in Acupuncture Preconditioning-Induced Ischemic Tolerance". Advanced Materials Research 554-556 (julio de 2012): 1650–55. http://dx.doi.org/10.4028/www.scientific.net/amr.554-556.1650.
Resumen
Abstract Objective To investigate the expression of erythropoietin (EPO) after acupuncture preconditioning plus focal cerebral ischemia treatment. Methods Rat focal cerebral ischemia model and acupuncture preconditioning model were established. Animals were randomly assigned into different groups: control (focal cerebral ischemia) and acupuncture preconditioning plus focal cerebral ischemia, with 8 rats for each group. The expression of EPO after different treatments was determined by histological examination, immunohistochemistry and in situ hybridization. Results The mRNA and protein expressions of EPO could be detected in survival and necrotic neurons, glia as well as vascular endothelial cells. Focal cerebral ischemia promoted the expression of EPO. Significant enhanced EPO level was found in the ischemic peripheral zone after acupuncture preconditioning (P < 0.05). Conclusion Our results demonstrated that acupuncture preconditioning enhanced the expression of EPO in neurons, glia and vascular endothelial cells the ischemic peripheral zone, suggesting the involvement of EPO in acupuncture preconditioning-induced neuroprotection following focal cerebral ischemia. EPO may exert neuroprotective effects through promoting neurotrophic support and angiogenesis.
6
Kitagawa, Kazuo, Masayasu Matsumoto, Takuma Mabuchi, Yoshiki Yagita, Toshiho Ohtsuki, Masatsugu Hori y Takehiko Yanagihara. "Deficiency of Intercellular Adhesion Molecule 1 Attenuates Microcirculatory Disturbance and Infarction Size in Focal Cerebral Ischemia". Journal of Cerebral Blood Flow & Metabolism 18, n.º 12 (diciembre de 1998): 1336–45. http://dx.doi.org/10.1097/00004647-199812000-00008.
Resumen
Recent evidence has shown crucial roles for cell-adhesion molecules in inflammation-induced rolling, adhesion, and accumulation of neutrophils in tissue. Intercellular adhesion molecule-1 (ICAM-1) is one of these adhesion molecules. Previous studies have shown marked reduction in the size of infarction after focal cerebral ischemia by depletion of granulocytes and administration of the antibody against ICAM-1. In the present study we investigated the role of ICAM-1 in the size of ischemic lesions, accumulation of granulocytes, and microcirculatory compromise in focal cerebral ischemia by using ICAM-1–knockout mice. Ischemic lesions were significantly mitigated in knockout mice after permanent and transient focal ischemia, even though the number of granulocytes in the infarcted tissue was almost the same between knockout and wild-type mice. Depletion of granulocytes further decreased the size of ischemic lesions after transient focal ischemia in ICAM-1–knockout mice. Microcirculation was reduced after focal ischemia, but it was better preserved in the cerebral cortex of knockout mice than that of wild-type mice. The present study demonstrated that ICAM-1 played a role in microcirculatory failure and subsequent development and expansion of infarction after focal cerebral ischemia. However, it is highly unlikely that ICAM-1 played a key role in accumulation of granulocytes after focal cerebral ischemia.
7
Duarte, Sinésio Grace, Antônio Dorival Campos y Benedicto Oscar Colli. "Functional evaluation of temporary focal cerebral ischemia: experimental model". Arquivos de Neuro-Psiquiatria 61, n.º 3B (septiembre de 2003): 751–56. http://dx.doi.org/10.1590/s0004-282x2003000500009.
Resumen
OBJECTIVE: Despite cerebral ischemia being a frequent clinical pathologic state, the tolerance of neural tissue to oxygen absence and to reperfusion is controversial. This study aims to evaluate the effects of focal cerebral ischemia/reperfusion, by analyzing the mitochondrial respiration. METHOD: Sixty-four adult rats underwent focal cerebral ischemia by middle cerebral artery occlusion, during 15, 30 and 60 minutes, followed by 10 minutes or 19 hours of reperfusion. The effects of ischemia were analyzed measuring the O2 consumption by mitochondria in the ischemic and non-ischemic areas. RESULTS: There was compromise of the mitochondrial respiration after 30 and 60 minutes of ischemia, followed by 10 minutes of reperfusion but there was no alteration in this function after 19 hours of reperfusion. CONCLUSION: Compromise of the mitochondrial function occurred after 30 minutes of ischemia but, until one hour of ischemia, if the reperfusion was prolonged there was no evidence of ischemic/reperfusion injuries.
8
del Zoppo, Gregory J. y Takuma Mabuchi. "Cerebral Microvessel Responses to Focal Ischemia". Journal of Cerebral Blood Flow & Metabolism 23, n.º 8 (agosto de 2003): 879–94. http://dx.doi.org/10.1097/01.wcb.0000078322.96027.78.
Resumen
Cerebral microvessels have a unique ultrastructure form, which allows for the close relationship of the endothelium and blood elements to the neurons they serve, via intervening astrocytes. To focal ischemia, the cerebral microvasculature rapidly displays multiple dynamic responses. Immediate events include breakdown of the primary endothelial cell permeability barrier, with transudation of plasma, expression of endothelial cell-leukocyte adhesion receptors, loss of endothelial cell and astrocyte integrin receptors, loss of their matrix ligands, expression of members of several matrix-degrading protease families, and the appearance of receptors associated with angiogenesis and neovascularization. These events occur pari passu with neuron injury. Alterations in the microvessel matrix after the onset of ischemia also suggest links to changes in nonvascular cell viability. Microvascular obstruction within the ischemic territory occurs after occlusion and reperfusion of the feeding arteries (“focal no-reflow” phenomenon). This can result from extrinsic compression and intravascular events, including leukocyte(-platelet) adhesion, platelet-fibrin interactions, and activation of coagulation. All of these events occur in microvessels heterogeneously distributed within the ischemic core. The panorama of acute microvessel responses to focal cerebral ischemia provide opportunities to understand interrelationships between neurons and their microvascular supply and changes that underlie a number of central nervous system neurodegenerative disorders.
9
Siesjö, Bo K. "Pathophysiology and treatment of focal cerebral ischemia". Journal of Neurosurgery 77, n.º 3 (septiembre de 1992): 337–54. http://dx.doi.org/10.3171/jns.1992.77.3.0337.
Resumen
✓ The mechanisms that give rise to ischemic brain damage have not been definitively determined, but considerable evidence exists that three major factors are involved: increases in the intercellular cytosolic calcium concentration (Ca++i), acidosis, and production of free radicals. A nonphysiological rise in Ca++i due to a disturbed pump/leak relationship for calcium is believed to cause cell damage by overactivation of lipases and proteases and possibly also of endonucleases, and by alterations of protein phosphorylation, which secondarily affects protein synthesis and genome expression. The severity of this disturbance depends on the density of ischemia. In complete or near-complete ischemia of the cardiac arrest type, pump activity has ceased and the calcium leak is enhanced by the massive release of excitatory amino acids. As a result, multiple calcium channels are opened. This is probably the scenario in the focus of an ischemic lesion due to middle cerebral artery occlusion. Such ischemic tissues can be salvaged only by recirculation, and any brain damage incurred is delayed, suggesting that the calcium transient gives rise to sustained changes in membrane function and metabolism. If the ischemia is less dense, as in the penumbral zone of a focal ischemic lesion, pump failure may be moderate and the leak may be only slightly or intermittently enhanced. These differences in the pump/leak relationship for calcium explain why calcium and glutamate antagonists may lack effect on the cardiac arrest type of ischemia, while decreasing infarct size in focal ischemia. The adverse effects of acidosis may be exerted by several mechanisms. When the ischemia is sustained, acidosis may promote edema formation by inducing Na+ and Cl− accumulation via coupled Na+/H+ and Cl−/HCO3− exchange; however, it may also prevent recovery of mitochondrial metabolism and resumption of H+ extrusion. If the ischemia is transient, pronounced intraischemic acidosis triggers delayed damage characterized by gross edema and seizures. Possibly, this is a result of free-radical formation. If the ischemia is moderate, as in the penumbral zone of a focal ischemic lesion, the effect of acidosis is controversial. In fact, enhanced glucolysis may then be beneficial. Although free radicals have long been assumed to be mediators of ischemic cell death, it is only recently that more substantial evidence of their participation has been produced. It now seems likely that one major target of free radicals is the microvasculature, and that free radicals and other mediators of inflammatory reactions (such as platelet-activating factor) aggravate the ischemic lesion by causing microvascular dysfunction and blood-brain barrier disruption. Solid experimental evidence exists that the infarct resulting from middle cerebral artery occlusion can be reduced by glutamate antagonists, by several calcium antagonists, and by some drugs acting on Ca++ and Na+ influx. In addition, published reports hint that qualitatively similar results are obtained with drugs whose sole or main effect is to scavenge free radicals. Thus, there is substantial experimental evidence that the ischemic lesions due to middle cerebral artery occlusion can be ameliorated by drugs, sometimes dramatically; however, the therapeutic window seems small, maximally 3 to 6 hours. This suggests that if these therapeutic principles are to be successfully applied to the clinical situation, patient management must change.
10
Codaccioni, Jean-Laurent, Lionel J. Velly, Chahrazad Moubarik, Nicolas J. Bruder, Pascale S. Pisano y Benjamin A. Guillet. "Sevoflurane Preconditioning against Focal Cerebral Ischemia". Anesthesiology 110, n.º 6 (1 de junio de 2009): 1271–78. http://dx.doi.org/10.1097/aln.0b013e3181a1fe68.
Resumen
Background Preconditioning the brain with volatile anesthetics seems to be a viable option for reducing ischemic cerebral injury. However, it is uncertain whether this preconditioning effect extends over a longer period of time. The purpose of this study was to determine if sevoflurane preconditioning offers durable neuroprotection against cerebral ischemia. Methods Rats (Sprague-Dawley) were randomly allocated to two groups: nonpreconditioned control group (n = 44) and preconditioned group (n = 45) exposed to 2.7 vol% sevoflurane (45 min) 60 min before surgery. Animals in both groups were anesthetized with 3.0 vol% sevoflurane and subjected to transient middle cerebral artery occlusion. After 60 min of awake focal ischemia, the filament was removed. Functional neurologic outcome (range 0-18; 0 = no deficit), cerebral infarct size (Nissl staining), and apoptosis (Terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick-end labeling; cleaved caspase-3 staining) were evaluated at 3, 7, and 14 days after ischemia. Results Sevoflurane preconditioning significantly improved functional outcome and reduced infarct volume (109 +/- 43 vs. 148 +/- 56 mm(3)) 3 days after ischemia compared to the control group. However, after 7- and 14-day recovery periods, no significant differences were observed between groups. The number of apoptotic cells was significantly lower in the preconditioned group than in the control group after 3- and 7-day recovery periods. Fourteen days after ischemia, no differences were observed between groups. Conclusion In this model of transient focal cerebral ischemia, sevoflurane preconditioning induced effective but transient neuroprotective effects. Sevoflurane preconditioning also decreased ischemia-induced apoptosis in a more sustained way because it was observed up to 7 days after injury.
11
Han, Xue Mei, Hong Tao Wei y Song Yan Liu. "Functional Role of HIF-1α in Hypoxic Preconditioning-Induced Neuroprotection against Focal Cerebral Ischemia". Advanced Materials Research 554-556 (julio de 2012): 1762–67. http://dx.doi.org/10.4028/www.scientific.net/amr.554-556.1762.
Resumen
Objective To investigate the expression of HIF-1α after permenent focal cerebral ischemia and to explore the role of HIF-1α in hypoxic preconditioning-induced neuroprotection. Methods Rat focal cerebral ischemia model and hypoxic preconditioning models were established. Animals were randomly divided into four groups: healthy control, hypoxic preconditioning (3 h of 8% O2/92% N2 treatment), focal cerebral ischemia (6 h, 1 d, 3 d or 7 d) and hypoxic preconditioning + focal cerebral ischemia (6 h, 1 d, 3 d or 7 d). The expression of HIF-1α after different treatments was determined by histological examination, immunohistochemistry and in situ hybridization. Results The mRNA and protein expressions of HIF-1α could be detected in survival and necrotic neurons, glia as well as vascular endothelial cells. Hypoxic preconditioning significantly promoted the expression of HIF-1α after focal cerebral ischemia, especially in ischemic peripheral zone (P < 0.05).
12
Siesjö, Bo K. "Pathophysiology and treatment of focal cerebral ischemia". Journal of Neurosurgery 77, n.º 2 (agosto de 1992): 169–84. http://dx.doi.org/10.3171/jns.1992.77.2.0169.
Resumen
✓ This article examines the pathophysiology of lesions caused by focal cerebral ischemia. Ischemia due to middle cerebral artery occlusion encompasses a densely ischemic focus and a less densely ischemic penumbral zone. Cells in the focus are usually doomed unless reperfusion is quickly instituted. In contrast, although the penumbra contains cells “at risk.” these may remain viable for at least 4 to 8 hours. Cells in the penumbra may be salvaged by reperfusion or by drugs that prevent an extension of the infarction into the penumbral zone. Factors responsible for such an extension probably include acidosis, edema, K+/Ca++ transients, and inhibition of protein synthesis. Central to any discussion of the pathophysiology of ischemic lesions is energy depletion. This is because failure to maintain cellular adenosine triphosphate (ATP) levels leads to degradation of macromolecules of key importance to membrane and cytoskeletal integrity, to loss of ion homeostasis, involving cellular accumulation of Ca++, Na+, and Cl−, with osmotically obligated water, and to production of metabolic acids with a resulting decrease in intra- and extracellular pH. In all probability, loss of cellular calcium homeostasis plays an important role in the pathogenesis of ischemic cell damage. The resulting rise in the free cytosolic intracellular calcium concentration (Ca++) depends on both the loss of calcium pump function (due to ATP depletion), and the rise in membrane permeability to calcium. In ischemia, calcium influx occurs via multiple pathways. Some of the most important routes depend on activation of receptors by glutamate and associated excitatory amino acids released from depolarized presynaptic endings. However, ischemia also interferes with the intracellular sequestration and binding of calcium, thereby contributing to the rise in intracellular Ca++. A second key event in the ischemic tissue is activation of anaerobic glucolysis. The main reason for this activation is inhibition of mitochondrial metabolism by lack of oxygen; however, other factors probably contribute. For example, there is a complex interplay between loss of cellular calcium homeostasis and acidosis. On the one hand, a rise in intracellular Ca++ is apt to cause mitochondrial accumulation of calcium. This must interfere with ATP production and enhance anaerobic glucolysis. On the other hand, acidosis must interfere with calcium binding, thereby contributing to the rise in intracellular Ca++.
13
Siesjö, Bo K. "Pathophysiology and treatment of focal cerebral ischemia". Journal of Neurosurgery 108, n.º 3 (marzo de 2008): 616–31. http://dx.doi.org/10.3171/jns/2008/108/3/0616.
Resumen
✓ This article examines the pathophysiology of lesions caused by focal cerebral ischemia. Ischemia due to middle cerebral artery occlusion encompasses a densely ischemic focus and a less densely ischemic penumbral zone. Cells in the focus are usually doomed unless reperfusion is quickly instituted. In contrast, although the penumbra contains cells “at risk,” these may remain viable for at least 4 to 8 hours. Cells in the penumbra may be salvaged by reperfusion or by drugs that prevent an extension of the infarction into the penumbral zone. Factors responsible for such an extension probably include acidosis, edema, K+/Ca++ transients, and inhibition of protein synthesis. Central to any discussion of the pathophysiology of ischemic lesions is energy depletion. This is because failure to maintain cellular adenosine triphosphate (ATP) levels leads to degradation of macromolecules of key importance to membrane and cytoskeletal integrity, to loss of ion homeostasis, involving cellular accumulation of Ca++, Na+, and Cl−, with osmotically obligated water, and to production of metabolic acids with a resulting decrease in intra- and extracellular pH. In all probability, loss of cellular calcium homeostasis plays an important role in the pathogenesis of ischemic cell damage. The resulting rise in the free cytosolic intracellular calcium concentration (Ca++) depends on both the loss of calcium pump function (due to ATP depletion), and the rise in membrane permeability to calcium. In ischemia, calcium influx occurs via multiple pathways. Some of the most important routes depend on activation of receptors by glutamate and associated excitatory amino acids released from depolarized presynaptic endings. However, ischemia also interferes with the intracellular sequestration and binding of calcium, thereby contributing to the rise in intracellular Ca++. A second key event in the ischemic tissue is activation of anaerobic glucolysis. The main reason for this activation is inhibition of mitochondrial metabolism by lack of oxygen; however, other factors probably contribute. For example, there is a complex interplay between loss of cellular calcium homeostasis and acidosis. On the one hand, a rise in intracellular Ca++ is apt to cause mitochondrial accumulation of calcium. This must interfere with ATP production and enhance anaerobic glucolysis. On the other hand, acidosis must interfere with calcium binding, thereby contributing to the rise in intracellular Ca++.
14
Sharp, Frank R., Aigang Lu, Yang Tang y David E. Millhorn. "Multiple Molecular Penumbras after Focal Cerebral Ischemia". Journal of Cerebral Blood Flow & Metabolism 20, n.º 7 (julio de 2000): 1011–32. http://dx.doi.org/10.1097/00004647-200007000-00001.
Resumen
Though the ischemic penumbra has been classically described on the basis of blood flow and physiologic parameters, a variety of ischemic penumbras can be described in molecular terms. Apoptosis-related genes induced after focal ischemia may contribute to cell death in the core and the selective cell death adjacent to an infarct. The HSP70 heat shock protein is induced in glia at the edges of an infarct and in neurons often at some distance from the infarct. HSP70 proteins are induced in cells in response to denatured proteins that occur as a result of temporary energy failure. Hypoxia-inducible factor (HIF) is also induced after focal ischemia in regions that can extend beyond the HSP70 induction. The region of HIF induction is proposed to represent the areas of decreased cerebral blood flow and decreased oxygen delivery. Immediate early genes are induced in cortex, hippocampus, thalamus, and other brain regions. These distant changes in gene expression occur because of ischemia-induced spreading depression or depolarization and could contribute to plastic changes in brain after stroke.
15
Jacewicz, Michael, Marika Kiessling y William A. Pulsinelli. "Selective Gene Expression in Focal Cerebral Ischemia". Journal of Cerebral Blood Flow & Metabolism 6, n.º 3 (junio de 1986): 263–72. http://dx.doi.org/10.1038/jcbfm.1986.48.
Resumen
Regional patterns of protein synthesis were examined in rat cortex made ischemic by the occlusion of the right common carotid and middle cerebral arteries. At 2 h of ischemia, proteins were pulse labeled with intracortical injections of a mixture of [3H]leucine, [3H]isoleucine, and [3H]proline. Newly synthesized proteins were analyzed by two-dimensional gel fluorography, and the results correlated with local CBF, measured with [14C]iodoantipyrine as tracer. Small blood flow reductions (CBF = 50–80 ml 100 g−1 min−1) were accompanied by a modest inhibition in synthesis of many proteins and a marked increase in one protein (Mr 27,000). With further reduction in blood flow (CBF = 40 ml 100 g−1 min−1), synthesis became limited to a small group of proteins (Mr 27,000, 34,000, 73,000, 79,000, and actin) including two new polypeptides (Mr 55,000 and 70,000). Severe ischemia (CBF = 15–25 ml 100 g−1 min−1) caused the isoelectric modification of several proteins (Mr 44,000, 55,000, and 70,000) and induced synthesis of another protein (Mr 40,000). Two polypeptides (Mr 27,000 and 70,000) dominated residual protein synthesis in severe ischemia. The changes in protein synthesis induced by different grades of ischemia most likely comprise a variation of the so-called “heat shock” or “stress” response found in all eukaryotic cells subjected to adverse conditions. Since heat shock genes are known to confer partial protection against anoxia and a variety of other noxious insults, their induction may be a factor in limiting the extent of ischemic tissue damage.
16
Meng, Wei, Xiaoying Wang, Minoru Asahi, Tsuneo Kano, Kazuko Asahi, Robert H. Ackerman y Eng H. Lo. "Effects of Tissue Type Plasminogen Activator in Embolic versus Mechanical Models of Focal Cerebral Ischemia in Rats". Journal of Cerebral Blood Flow & Metabolism 19, n.º 12 (diciembre de 1999): 1316–21. http://dx.doi.org/10.1097/00004647-199912000-00004.
Resumen
Tissue type plasminogen activator (tPA) can be effective therapy for embolic stroke by restoring cerebral perfusion. However, a recent experimental study showed that tPA increased infarct size in a mouse model of transient focal ischemia, suggesting a possible adverse effect of tPA on ischemic tissue per se. In this report, the effects of tPA in two rat models of cerebral ischemia were compared. In experiment 1, rats were subjected to focal ischemia via injection of autologous clots into the middle cerebral artery territory. Two hours after clot injection, rats were treated with 10 mg/kg tPA or normal saline. Perfusion-sensitive computed tomography scanning showed that tPA restored cerebral perfusion in this thromboembolic model. Treatment with tPA significantly reduced ischemic lesion volumes measured at 24 hours by >60%. In experiment 2, three groups of rats were subjected to focal ischemia via a mechanical approach in which a silicon-coated filament was used intraluminally to occlude the origin of the middle cerebral artery. In two groups, the filament was withdrawn after 2 hours to allow for reperfusion, and then rats were randomly treated with 10 mg/kg tPA or normal saline. In the third group, rats were not treated and the filament was not withdrawn so that permanent focal ischemia was present. In this experiment, tPA did not significantly alter lesion volumes after 2 hours of transient focal ischemia. In contrast, permanent ischemia significantly increased lesion volumes by 55% compared with transient ischemia. These results indicate that in these rat models of focal cerebral ischemia, tPA did not have detectable negative effects. Other potentially negative effects of tPA may be dependent on choice of animal species and model systems.
17
Barone, F. C., M. Y. T. Globus, W. J. Price, R. F. White, B. L. Storer, G. Z. Feuerstein, R. Busto y E. H. Ohlstein. "Endothelin Levels Increase in Rat Focal and Global Ischemia". Journal of Cerebral Blood Flow & Metabolism 14, n.º 2 (marzo de 1994): 337–42. http://dx.doi.org/10.1038/jcbfm.1994.41.
Resumen
Endothelin-1, a peptide exhibiting extremely potent cerebral vasoactive properties, is elevated in the cerebrospinal fluid after hemorrhagic stroke and implicated in cerebral vasospasm. The purpose of this study was to determine changes in endothelin in ischemic rat brain by assaying endothelin tissue and extracellular levels. Immunoreactive endothelin levels in ischemic brain tissue following permanent or transient focal ischemia produced by middle cerebral artery occlusion was determined. In addition, endothelin levels were assayed in striatal extracellular fluid collected by microdialysis before, during, and after global ischemia produced by two-vessel occlusion combined with hypotension. Twenty-four hours after the onset of permanent middle cerebral artery occlusion, the ischemic cortex level (0.58 ± 0.27 fmol/mg protein) of immunoreactive endothelin was significantly (p < 0.05) increased, by 100%, over that in the nonischemic cortex (0.29 ± 0.13 fmol/mg protein). Transient artery occlusion for 80 min with reperfusion for 24 h also resulted in a similar significant (p < 0.05) increase, 78%, in immunoreactive endothelin in the ischemic zone. Global forebrain ischemia significantly (p < 0.05) increased the level of immunoreactive endothelin collected in striatal microdialysis perfusate, from a basal level of 14.6 ± 6.7 to 26.5 ± 7.7 and 26.2 ± 7.4 amol/μl (i.e. 82 and 79%). These changes reflect the relative picomolar extracellular concentration increases during ischemia and following reperfusion, respectively. This is the first demonstration of elevated levels of endothelin in focal ischemic tissue and in the extracellular fluid in global ischemia and suggests a role of the peptide in ischemic and postischemic derangements of cerebral vascular function and tissue injury.
18
Yagita, Yoshiki, Kazuo Kitagawa, Naoki Oyama, Toshiro Yukami, Akihiro Watanabe, Tsutomu Sasaki y Hideki Mochizuki. "Functional Deterioration of Endothelial Nitric Oxide Synthase after Focal Cerebral Ischemia". Journal of Cerebral Blood Flow & Metabolism 33, n.º 10 (3 de julio de 2013): 1532–39. http://dx.doi.org/10.1038/jcbfm.2013.112.
Resumen
Endothelial nitric oxide synthase (eNOS) dysfunction is related to secondary injury and lesion expansion after cerebral ischemia. To date, there are few reports about postischemic alterations in the eNOS regulatory system. The purpose of the present study was to clarify eNOS expression, Ser1177 phosphorylation, and monomer formation after cerebral ischemia. Male Wistar rats were subjected to transient focal cerebral ischemia. Endothelial nitric oxide synthase messenger RNA (mRNA) and protein expression increased ~ 8-fold in the ischemic lesion. In the middle cerebral artery core, eNOS-Ser1177 phosphorylation increased 6 hours after ischemia; however, there was an approximately 90% decrease in eNOS-Ser1177 phosphorylation observed 24 hours after ischemia that continued until at least 7 days after ischemia. Endothelial nitric oxide synthase monomer formation also increased 24 and 48 hours after ischemia ( P<0.05), and protein nitration progressed in parallel with monomerization. To assess the effect of a neuroprotective agent on eNOS dysfunction, we evaluated the effect of fasudil, a Rho-kinase inhibitor, on eNOS phosphorylation and dimerization. Postischemic treatment with fasudil suppressed lesion expansion and dephosphorylation and monomer formation of eNOS. In conclusion, functional deterioration of eNOS progressed after cerebral ischemia. Rho-kinase inhibitors can reduce ischemic lesion expansion as well as eNOS dysfunction in the ischemic brain.
19
Ye, Zhouheng, Bradley P. Ander, Frank R. Sharp y Xinhua Zhan. "Cleaved β-Actin May Contribute to DNA Fragmentation Following Very Brief Focal Cerebral Ischemia". Journal of Neuropathology & Experimental Neurology 77, n.º 3 (2 de febrero de 2018): 260–65. http://dx.doi.org/10.1093/jnen/nly003.
Resumen
Abstract Our previous study demonstrated caspase independent DNA fragmentation after very brief cerebral ischemia, the mechanism of which was unclear. In this study, we explore whether actin is cleaved following focal cerebral ischemia, and whether these structural changes of actin might modulate DNA fragmentation observed following focal ischemia. Results showed that a cleaved β-actin fragment was identified in brains of rats 24 hours following 10-minute and 2-hour focal ischemia. Though granzyme B and caspase-3 cleaved β-actin in vitro, the fragment size of β-actin cleaved by granzyme B was the same as those found after 10-minute and 2-hour focal ischemia. This was consistent with increases of granzyme B activity after 10-minute and 2-hour ischemia compared with controls. Cerebral extracts from 10-minute and 2-hour ischemic brains degraded DNA in vitro. Adding intact β-actin to these samples completely abolished DNA degradation from the 10-minute ischemia group but not from the 2-hour ischemia group. We concluded that β-actin is likely cleaved by granzyme B by 24 hours following 10-minute and 2-hour focal cerebral ischemia. Intact β-actin inhibits DNase, and cleavage of β-actin activates DNase, which leads to DNA fragmentation observed in the brain following very brief focal ischemia.
20
Asahi, Minoru, Kazuko Asahi, Jae-Chang Jung, Gregory J. del Zoppo, M. Elizabeth Fini y Eng H. Lo. "Role for Matrix Metalloproteinase 9 after Focal Cerebral Ischemia: Effects of Gene Knockout and Enzyme Inhibition with BB-94". Journal of Cerebral Blood Flow & Metabolism 20, n.º 12 (diciembre de 2000): 1681–89. http://dx.doi.org/10.1097/00004647-200012000-00007.
Resumen
It has been shown recently that matrix metalloproteinases (MMPs) are elevated after cerebral ischemia. In the current study, we investigated the pathophysiologic role for MMP-9 (gelatinase B, EC.3.4.24.35) in a mouse model of permanent focal cerebral ischemia, using a combination of genetic and pharmacologic approaches, Zymography and Western blot analysis demonstrated that MMP-9 protein levels were rapidly up-regulated in brain after ischemic onset. Reverse transcription polymerase chain reaction showed increased transcription of MMP-9. There were no differences in systemic hemodynamic parameters and gross cerebrovascular anatomy between wild type mice and mutant mice with a targeted knockout of the MMP-9 gene. After induction of focal ischemia, similar reductions in cerebral blood flow were obtained. In the MMP-9 knockout mice, ischemic lesion volumes were significantly reduced compared with wild type littermates in male and female mice. In normal wild type mice, the broad spectrum MMP inhibitor BB-94 (batimastat) also significantly reduced ischemic lesion size, However, BB-94 had no detectable protective effect when administered to MMP-9 knockout mice subjected to focal cerebral ischemia. These data demonstrate that MMP-9 plays a deleterious role in the development of brain injury after focal ischemia.
21
Tranmer, Bruce I., Ted S. Keller, Glenn W. Kindt y David Archer. "Loss of cerebral regulation during cardiac output variations in focal cerebral ischemia". Journal of Neurosurgery 77, n.º 2 (agosto de 1992): 253–59. http://dx.doi.org/10.3171/jns.1992.77.2.0253.
Resumen
✓ Focal cerebral ischemia was induced in anesthetized macaque monkeys by unilateral middle cerebral artery occlusion. The effect of blood volume expansion by a colloid agent and subsequent exsanguination to baseline cardiac output (CO) on local cerebral blood flow (CBF) was measured by the hydrogen clearance technique in both ischemic and nonischemic brain regions. Cardiac output was increased to maximum levels (159% ± 92%, mean ± standard error of the mean) by blood volume expansion with the colloid agent hetastarch, and was then reduced a similar amount (166% ± 82%) by exsanguination during the ischemic period. Local CBF in ischemic brain regions varied directly with CO, with a correlation coefficient of 0.89 (% change CBF/% change CO), while CBF in nonischemic brain was not affected by upward or downward manipulations of CO. The difference in these responses between ischemic and nonischemic brain was highly significant (p < 0.001). The results of this study show a profound loss of regulatory control in ischemic brain in response to alterations in CO, thereby suggesting that blood volume variations may cause significant changes in the intensity of ischemia. It is proposed that CO monitoring and manipulation may be vital for optimum care of patients with acute cerebral ischemia.
22
Cole, Daniel J., Randall M. Schell, John C. Drummond, Piyush M. Patel y Suzzanne Marcantonio. "Focal Cerebral Ischemia in Rats". Journal of Neurosurgical Anesthesiology 4, n.º 2 (abril de 1992): 78–84. http://dx.doi.org/10.1097/00008506-199204000-00002.
23
Prencipe, Massimiliano, Antonio Carolei, Gian Luigi Lenzi y Cesare Fieschi. "Focal Cerebral Ischemia and Migraine". Cephalalgia 5, n.º 2_suppl (mayo de 1985): 21–22. http://dx.doi.org/10.1177/03331024850050s204.
Resumen
Consistent literature data on the cerebrovascular risk in migraineous patients are lacking. Available preliminary clinical data (Italian Cooperative Cross-Sectional Case-Control Study) suggest that migraine can hardly be considered a relevant pathogenetic associated risk factor of focal cerebral ischemia.
24
Cole, Daniel J., Randall M. Schell, John C. Drummond y Lowell Reynolds. "Focal Cerebral Ischemia in Rats". Anesthesiology 78, n.º 2 (1 de febrero de 1993): 335–42. http://dx.doi.org/10.1097/00000542-199302000-00018.
25
Zhan, Xinhua, Bradley P. Ander, Glen Jickling, Renée Turner, Boryana Stamova, Huichun Xu, Dazhi Liu, Ryan R. Davis y Frank R. Sharp. "Brief Focal Cerebral Ischemia That Simulates Transient Ischemic Attacks in Humans Regulates Gene Expression in Rat Peripheral Blood". Journal of Cerebral Blood Flow & Metabolism 30, n.º 1 (9 de septiembre de 2009): 110–18. http://dx.doi.org/10.1038/jcbfm.2009.189.
Resumen
Blood gene expression profiles of very brief (5 and 10 mins) focal ischemia that simulates transient ischemic attacks in humans were compared with ischemic stroke (120 mins focal ischemia), sham, and naïve controls. The number of significantly regulated genes after 5 and 10 mins of cerebral ischemia was 39 and 160, respectively (fold change ⩾∣1.5∣ and P<0.05). There were 103 genes common to brief focal ischemia and ischemic stroke. Ingenuity pathway analysis showed that genes regulated in the 5 mins group were mainly involved in small molecule biochemistry. Genes regulated in the 10 mins group were involved in cell death, development, growth, and proliferation. Such genes were also regulated in the ischemic stroke group. Genes common to ischemia were involved in the inflammatory response, immune response, and cell death—indicating that these pathways are a feature of focal ischemia, regardless of the duration. These results provide evidence that brief focal ischemia differentially regulates gene expression in the peripheral blood in a manner that could distinguish brief focal ischemia from ischemic stroke and controls in rats. We postulate that this will also occur in humans.
26
Pfefferkorn, T., B. Staufer, M. Liebetrau, G. Bültemeier, M. R. Vosko, C. Zimmermann y G. F. Hamann. "Plasminogen Activation in Focal Cerebral Ischemia and Reperfusion". Journal of Cerebral Blood Flow & Metabolism 20, n.º 2 (febrero de 2000): 337–42. http://dx.doi.org/10.1097/00004647-200002000-00015.
Resumen
In focal cerebral ischemia the plasminogen-plasmin system plays a role in the fibrinolysis of vessel-occluding clots and also in the proteolysis of extracellular matrix components, which potentially contributes to brain edema and bleeding complications. The authors investigated the plasminogen activation after middle cerebral artery occlusion with and without reperfusion (reperfusion intervals 9 and 24 hours) in rats by histologic zymography and compared areas of increased plasminogen activation to areas of structural injury, which were detected immunohistochemically. After 3 hours of ischemia, increased plasminogen activation was observed in the ischemic hemisphere. The affected area measured 5.2% ± 8.5% and 19.4% ± 30.1% of the total basal ganglia and cortex area, respectively. Reperfusion for 9 hours after 3 hours of ischemia led to a significant expansion of plasminogen activation in the basal ganglia (68.8% ± 42.2%, P < 0.05) but not in the cortex (43.0% ± 34.6%, P = 0.394). In the basal ganglia, areas of increased plasminogen activation were related to areas of structural injury ( r = 0.873, P < 0.001). No such correlation was found in the cortex ( r = 0.299, P = 0.228). In this study, increased plasminogen activation was demonstrated early in focal cerebral ischemia. This activation may promote early secondary edema formation and also secondary hemorrhage after ischemic stroke.
27
Malisza, K. L., P. Kozlowski y J. Peeling. "A review of in vivo 1H magnetic resonance spectroscopy of cerebral ischemia in rats". Biochemistry and Cell Biology 76, n.º 2-3 (1 de mayo de 1998): 487–96. http://dx.doi.org/10.1139/o98-041.
Resumen
A number of metabolic alterations are initiated by cerebral ischemia including dramatic increases in lactate concentration, decreases in N-acetylaspartate, choline, and creatine concentrations, as well as changes in amino acid levels. A review of proton nuclear magnetic resonance spectroscopy studies of focal and global cerebral ischemia in rats is presented here. In particular, studies in neonatal rats have shown that a continued elevation of lactate levels without recovery after hypoxia-ischemia or a decrease in N-acetylaspartate concentration at any time are indicative of deleterious outcome. Studies of the effect of temperature on ischemic damage in a model of focal ischemia showed that outcome improved with mild hypothermia. Again, lack of recovery of lactate upon reperfusion was shown to be indicative of poor outcome. Dichloroacetic acid was used to treat rats with focal ischemic damage. Animals subjected to transient ischemia that were treated with dichloroacetic acid showed significant decreases in lactate concentration.Key words: NMR, in vivo, rat, cerebral ischemia.
28
Yoshida, Mitsuyoshi, Kazuhiko Nakakimura, Ying Jun Cui, Mishiya Matsumoto y Takefumi Sakabe. "Adenosine A1 Receptor Antagonist and Mitochondrial ATP-Sensitive Potassium Channel Blocker Attenuate the Tolerance to Focal Cerebral Ischemia in Rats". Journal of Cerebral Blood Flow & Metabolism 24, n.º 7 (julio de 2004): 771–79. http://dx.doi.org/10.1097/01.wcb.0000122742.72175.1b.
Resumen
Involvement of adenosine and adenosine triphosphate-sensitive potassium (KATP) channels in the development of ischemic tolerance has been suggested in global ischemia, but has not been studied extensively in focal cerebral ischemia. This study evaluated modulating effects of adenosine A1 receptor antagonist DPCPX (8-cyclopentyl-1,3-dipropylxanthine) and mitochondrial KATP channel blocker 5HD (5-hydroxydecanoate) on the development of tolerance to focal cerebral ischemia in rats. Preconditioning with 30-minute middle cerebral artery occlusion (MCAO) reduced cortical and subcortical infarct volume following 120-minute MCAO (test ischemia) given 72 hours later. The neuroprotective effect of preconditioning was attenuated by 0.1 mg/kg DPCPX given before conditioning ischemia (30-minute MCAO), but no influence was provoked when it was administered before test ischemia. DPCPX had no effect on infarct volume after conditioning or test ischemia when given alone. The preconditioning-induced neuroprotection disappeared when 30 mg/kg 5HD was administered before test ischemia. These results suggest a possible involvement of adenosine A1 receptors during conditioning ischemia and of mitochondrial KATP channels during subsequent severe ischemia in the development of tolerance to focal cerebral ischemia.
29
Arai, Toshiyuki, Hisanari Ishii, Hiroko Mori, Kenjiro Mori y Shuji Kojima. "Effects of Neopterin on Focal Cerebral Ischemia In Rats". Pteridines 7, n.º 4 (noviembre de 1996): 157–59. http://dx.doi.org/10.1515/pteridines.1996.7.4.157.
Resumen
Summary We examined the effects of neopterin on focal cerebral ischemia induced by transient (2 h) occlusion of the middle cerebral artery (MCA) in rats. Neopterin was administered 10 min before reperfusion (3 mg/kg i.p). The ischemic damage was evaluated one week after the MCA occlusion by magnetic resonance imaging (MRI) and by the immunohistochemical reaction for microtubule-associated protein 2 (MAP2). The ischemic lesion detected by MRI was significantly smaller in the neopterin-treated group than in the non-treated group (n=4 in each group, p<0.05). However, the ischemic neuronal damage determined by MAP2 in the neopterintreated group was not significantly different from that in the non-treated group. Since MRI is thought to reflect the distribution of not only neurons but also glial cells, these results may indicate the effects of neopterin on the glial reaction in focal cerebral ischemia.
30
Charriaut-Marlangue, C., I. Margaill, M. Plotkine y Y. Ben-Ari. "Early Endonuclease Activation following Reversible Focal Ischemia in the Rat Brain". Journal of Cerebral Blood Flow & Metabolism 15, n.º 3 (mayo de 1995): 385–88. http://dx.doi.org/10.1038/jcbfm.1995.48.
Resumen
The structural changes that occur in chromatin DNA after ischemic brain injury are poorly understood. The presence of oligonucleosome fragments that are recognized as the characteristic DNA ladder has been demonstrated in global and focal ischemia, associated or not with random DNA fragmentation. Using pulsed-field gel electrophoresis, which improves DNA separation, we have now detected initial stages of DNA fragmentation that occur already 6 h after reversible focal cerebral ischemia in rats. This result confirms that internucleosomal DNA fragmentation precedes random DNA fragmentation in vulnerable striatal and cortical neurons following reversible focal cerebral ischemia.
31
Zhang, Fangyi, Sherry Xu y Costantino Iadecola. "Time Dependence of Effect of Nitric Oxide Synthase Inhibition on Cerebral Ischemic Damage". Journal of Cerebral Blood Flow & Metabolism 15, n.º 4 (julio de 1995): 595–601. http://dx.doi.org/10.1038/jcbfm.1995.73.
Resumen
Nitric oxide, a potent vasodilator and an inhibitor of platelet aggregation, may be beneficial in the early stages of focal cerebral ischemia as it may facilitate collateral blood flow to the ischemic territory. Accordingly, the effect of inhibition of nitric oxide synthesis on cerebral ischemic damage may vary depending on the timing of the inhibition relative to the induction of ischemia. We therefore studied the time course of the effect of nitric oxide synthesis inhibition on focal cerebral ischemic damage. The middle cerebral artery was permanently occluded in spontaneously hypertensive rats and the nitric oxide synthase (NOS) inhibitor nitro-l-arginine methyl ester (l-NAME) was administered systemically (3 mg/kg) <5 min or 2, 3, or 6 h later. Arterial pressure, rectal temperature, plasma glucose, and hematocrit were monitored. Infarct volume was determined on thioninstained sections 24 h after induction of ischemia. NOS activity was determined in cerebellum from the conversion of l-[3H]arginine to l-[3H]citrulline. Administration of l-NAME <5 min after arterial occlusion increased the infarct volume by 23 ± 14% (mean ± SD; p < 0.05, analysis of variance), while administration of l-NAME at 2 or 6 h did not affect the size of the infarct (p > 0.05). l-NAME administration 3 h after induction of ischemia reduced neocortical infarct size by 14 ± 11% (p < 0.05). l-NAME decreased cerebellar NOS activity comparably in all groups (range 16–25%). We conclude that the effects of inhibition of nitric oxide synthesis on focal cerebral ischemic damage are time dependent. Thus, inhibition of nitric oxide synthesis worsens ischemic damage when instituted shortly after induction of ischemia and does not affect or reduces damage at later times. The results support the hypothesis that the vascular actions of nitric oxide are beneficial only in the early stages of permanent focal cerebral ischemia.
32
Zhang, Zheng G., Wayne Tsang, Li Zhang, Cecylia Powers y Michael Chopp. "Temporal and spatial expression of neuropilin-1 in focal cerebral ischemic brain". Stroke 32, suppl_1 (enero de 2001): 317. http://dx.doi.org/10.1161/str.32.suppl_1.317-b.
Resumen
6 Neuropilin-1 is a receptor for vascular endothelial grow factor 165 isoform (VEGF 165 ) and plays roles in vasculogenesis and angiogenesis. Neuropilin-1 also binds to semaphorin III which is an inhibitor to axon guidance signal. To seek evidence that neuropilin-1 may play roles in ischemic brain, we examined the temporal and spatial profiles of its expression after focal cerebral ischemia. Male Wistar Rats (n=42) were subjected to 1h to 28 days of embolic middle cerebral artery (MCA) occlusion. Expression of neuropilin-1 was measured by Northern blot, in situ hybridization and immunohistochemistry. Upregulation of neuropilin-1 mRNA was detected in the ischemic hemisphere on Northern blots at 2h and persisted at least 28 days after ischemia. In situ hybridization revealed increased mRNA in the ischemic injury neurons around the boundary of the ischemic lesion at 4h to 48h after ischemia. Seven to twenty-eight days after ischemia, neuropilin-1 mRNA was localized to vessels within the ischemic lesion. Immunostaining for neuropilin-1 showed that some of the ischemic neurons were neuropilin-1 immunoreactive at 2h to 4h after ischemia, and cerebral blood vessels within the ischemic lesion were neuropilin-1 immunoreactive at 2 days to 28 days after ischemia. In addition, hypertrophic astrocytes around the boundary of the ischemic lesion were neuropilin-1 immunoreactive at 1 day to 28 days after ischemia. Double immunofluorescent staining for neuropilin-1 and VEGF showed that neuropilin-1 immunoreactive vessels and astrocytes exhibited VEGF immunoreactivity. Thus our data suggest that upregulation of neuropilin-1 may play a role in angiogenesis in ischemic brain.
33
Loddick, Sarah A., Andrew V. Turnbull y Nancy J. Rothwell. "Cerebral Interleukin-6 is Neuroprotective during Permanent Focal Cerebral Ischemia in the Rat". Journal of Cerebral Blood Flow & Metabolism 18, n.º 2 (febrero de 1998): 176–79. http://dx.doi.org/10.1097/00004647-199802000-00008.
Resumen
Interleukin-6 (IL-6) is a neurotrophic cytokine expressed in both neurons and glia. The present study shows that cerebral ischemia produced by permanent occlusion of the middle cerebral artery (MCAO) produces a dramatic increase in IL-6 bioactivity in the ischemic hemisphere within 2 hours of MCAO (167 ± 55 IU versus sham: 50 ± 35 IU), with further increases at 8 hours (3,456 ± 1,162 IU) and 24 hours (6,088 ± 1,772 IU). In a separate series of experiments, intracerebroventricular injection of recombinant IL-6 (3,100 or 31,000 IU) significantly reduced ischemic brain damage after MCAO (to 52% and 65% of controls, respectively). The large increase in endogenous IL-6 bioactivity in response to ischemia, together with the marked neuroprotection produced by exogenous IL-6 suggest that this cytokine is an important endogenous inhibitor of neuronal death during cerebral ischemia.
34
Noshita, Nobuo, Anders Lewén, Taku Sugawara y Pak H. Chan. "Evidence of Phosphorylation of Akt and Neuronal Survival after Transient Focal Cerebral Ischemia in Mice". Journal of Cerebral Blood Flow & Metabolism 21, n.º 12 (diciembre de 2001): 1442–50. http://dx.doi.org/10.1097/00004647-200112000-00009.
Resumen
The serine-threonine kinase, Akt, prevents apoptosis by phosphorylation at serine-473 in several cell systems. After phosphorylation, activated Akt inactivates other apoptogenic factors, such as Bad or caspase-9, thereby inhibiting cell death. The present study examined phosphorylation of Akt at serine-473 and DNA fragmentation after transient focal cerebral ischemia in mice subjected to 60 minutes of focal cerebral ischemia by intraluminal blockade of the middle cerebral artery. Phospho-Akt was analyzed by immunohistochemistry and Western blot analysis. The DNA fragmentation was evaluated by terminal deoxynucleotidyl transferase-mediated uridine 5′-triphosphate-biotin nick end-labeling (TUNEL). Immunohistochemistry showed the expression of phospho-Akt was markedly increased in the middle cerebral artery territory cortex at 4 hours of reperfusion compared with the control, whereas it was decreased by 24 hours. Western blot analysis showed a significant increase of phospho-Akt 4 hours after focal cerebral ischemia in the cortex, whereas phospho-Akt was decreased in the ischemic core. Double staining with phospho-Akt and TUNEL showed different cellular distributions of phospho-Akt and TUNEL-positive staining. Phosphorylation of Akt was prevented after focal cerebral ischemia by LY294002, a phosphatidylinositol 3-kinase inhibitor, which facilitated subsequent DNA fragmentation. These results suggest that phosphorylation of Akt may be involved in determining cell survival or cell death after transient focal cerebral ischemia.
35
Yan, Yiping, Robert J. Dempsey y Dandan Sun. "Na+-K+-Cl− Cotransporter in Rat Focal Cerebral Ischemia". Journal of Cerebral Blood Flow & Metabolism 21, n.º 6 (junio de 2001): 711–21. http://dx.doi.org/10.1097/00004647-200106000-00009.
Resumen
In cultured neurons, the authors previously demonstrated that the Na+-K+-Cl− cotransporter is significantly stimulated by elevated extracellular potassium and glutamate, which are important factors in cerebral ischemic damage. These findings led the authors to hypothesize that stimulation of the cotransporter after ischemia might result in Na+, K+, and Cl− influx, and might contribute to neuron damage. In the current study, the authors investigated such a role of the Na+-K+-Cl− cotransporter in focal cerebral ischemia. Cerebral ischemia was induced by 2-hour occlusion of the left middle cerebral artery (MCA) and 24-hour reperfusion in male spontaneously hypertensive rats (SHRs). Immunocytochemical staining and immunoblotting revealed an up-regulation of expression of the cotransporter protein in neurons in cortex at 24 hours of reperfusion. Artificial cerebral spinal fluid (aCSF) or 100 μmol/L bumetanide (a cotransporter inhibitor) in aCSF were continuously microdialyzed through a microdialysis probe into left cortices throughout 2-hour MCA occlusion and 24-hour reperfusion. Compared with the aCSF-treated group, infarction volume was significantly reduced in the bumetanide-treated group (25%, P < 0.05). In addition, brain water content in the bumetanide-treated brains was decreased by 70% ( P < 0.05). These results strongly suggest that the Na+-K+-Cl− cotransporter may play an important role in cerebral ischemic neuronal damage.
36
Lo, E. H., J. Rogowska, P. Bogorodzki, M. Trocha, K. Matsumoto, B. Saffran y G. L. Wolf. "Temporal Correlation Analysis of Penumbral Dynamics in Focal Cerebral Ischemia". Journal of Cerebral Blood Flow & Metabolism 16, n.º 1 (enero de 1996): 60–68. http://dx.doi.org/10.1097/00004647-199601000-00007.
Resumen
A novel temporal correlation technique was used to map the first-pass transit of iodinated contrast agents through the brain. Transit profiles after bolus injections were measured with dynamic computed tomography (CT) scanning (1 image/s over 50 s). A rabbit model of focal cerebral ischemia (n = 6) was used, and dynamic CT scans were performed at 30, 60, 90, and 120 min postocclusion. Within the ischemic core, no bolus transit was detectable, demonstrating that complete ischemia was present after arterial occlusion. In the periphery of the ischemic distribution, transit dynamics showed smaller peaks, broadened profiles, and overall delay in bolus transit. A cross-correlation method was used to generate maps of delays in ischemic transit profiles compared with normal transit profiles from the contralateral hemisphere. These maps showed that penumbral regions surrounding the ischemic core had significantly delayed bolus transit profiles. Enlargement of the ischemic core over time (from 30 to 120 min postocclusion) was primarily accomplished by the progressive deterioration of the penumbral regions. These results suggest that (a) temporal correlation methods can define regions of abnormal perfusion in focal cerebral ischemia, (b) peripheral regions of focal cerebral ischemia are characterized by delays in bolus transit profiles, and (c) these regions of bolus transit delay deteriorate over time and thus represent a hemodynamic penumbra.
37
Dirnagl, Ulrich y William Pulsinelli. "Autoregulation of Cerebral Blood Flow in Experimental Focal Brain Ischemia". Journal of Cerebral Blood Flow & Metabolism 10, n.º 3 (mayo de 1990): 327–36. http://dx.doi.org/10.1038/jcbfm.1990.61.
Resumen
The relationship between systemic arterial pressure (SAP) and neocortical microcirculatory blood-flow (CBF) in areas of focal cerebral ischemia was studied in 15 spontaneously hypertensive rats (SHRs) anesthetized with halothane (0.5%). Ischemia was induced by ipsilateral middle cerebral artery/common carotid artery occlusion and CBF was monitored continuously in the ischemic territory using laser-Doppler flowmetry during manipulation of SAP with I-norepinephrine (hypertension) or nitroprusside (hypotension). In eight SHRs not subjected to focal ischemia, we demonstrated that 0.5% halothane and the surgical manipulations did not impair autoregulation. Autoregulation was partly preserved in ischemic brain tissue with a CBF of >30% of preocclusion values. In areas where ischemic CBF was <30% of preocclusion values, autoregulation was completely lost. Changes in SAP had a greater influence on CBF in tissue areas where CBF ranged from 15 to 30% of baseline (9% change in CBF with each 10% change in SAP) than in areas where CBF was <15% of baseline (6% change in CBF with each 10% change in SAP). These findings demonstrate that the relationship between CBF and SAP in areas of focal ischemia is highly dependent on the severity of ischemia. Autoregulation is lost in a gradual manner until CBF falls below 30% of normal. In areas without autoregulation, the slope of the CBF/SAP relationship is inversely related to the degree of ischemia.
38
Chen, Jun, Steven H. Graham, Raymond L. Zhu y Roger P. Simon. "Stress Proteins and Tolerance to Focal Cerebral Ischemia". Journal of Cerebral Blood Flow & Metabolism 16, n.º 4 (julio de 1996): 566–77. http://dx.doi.org/10.1097/00004647-199607000-00006.
Resumen
Stress proteins are induced after a variety of neuronal injuries. The inducible 72-kDa heat shock protein (hsp70) is a stress protein that protects neurons from glutamate toxicity in vitro. Hsp70 has also been proposed to underlie the phenomenon of ischemic tolerance whereby brief sublethal intervals of global ischemia protect the hippocampus from subsequent lethal prolonged ischemia. To determine if the phenomenon of tolerance occurs in cortex after focal ischemia, the rat middle cerebral artery (MCA) was occluded by the suture method. Three 10-min intervals of transient ischemia (3 × 10-isc) separated by 45-min periods of reperfusion made up the most effective paradigm of preconditioning ischemia studied, and substantially reduced the volume of infarction 72 h after subsequent 100-min MCA occlusion. This approach induced protection if the interval between the 3 × 10-isc and the 100-min ischemia was 2, 3, or 5 days but not 1 or 7 days. Three 10-min intervals of transient ischemia alone produced minimal histological changes in the cortex at 72 h. Moreover, there were no significant changes in regional cerebral blood flow in the tolerant regions at 72 h after 3 × 10-isc before or during MCA occlusion. To explore the role of stress proteins in the induction of tolerance, expression of hsp70 and the glucose-regulated proteins grp75 and grp78 were studied. Samples from tolerant regions of the brain that had undergone preconditioning ischemia were evaluated at 1, 2, 3, 5, 7, and 14 days after 3 × 10-isc by Western blot analysis. The time course of hsp70 expression most closely correlated with tolerance. Hsp70 protein expression increased during times when tolerance was present (at 2–5 days) but did not increase thereafter (at 7 and 14 days). However, hsp70 was also increased before tolerance was present (at 1 day). Immunocytochemistry showed that hsp70 protein was expressed in neurons in the tolerant regions 24 h after 3 × 10-isc and was expressed in both neurons and glia after 72 h. Although immunocytochemistry suggested that there was increased neuronal expression of grp75 and grp78, no significant differences were found in protein expression as determined by Western blot before (at 1 day), during (at 2–5 days), and after (at 7 days and thereafter) tolerance. Thus, the time course of grp75 and grp78 expression did not correlate with that of tolerance. This model of ischemic tolerance is a useful method by which mechanisms of endogenous neuroprotection may be explored.
39
Matsushima, Kazushi, Matthew J. Hogan y Antoine M. Hakim. "Cortical Spreading Depression Protects against Subsequent Focal Cerebral Ischemia in Rats". Journal of Cerebral Blood Flow & Metabolism 16, n.º 2 (marzo de 1996): 221–26. http://dx.doi.org/10.1097/00004647-199603000-00006.
Resumen
The possibility that cortical spreading depression (CSD) may have neuroprotective action during subsequent focal cerebral ischemia was examined in rats. Three days before the imposition of focal cerebral ischemia CSDs were elicited by applying potassium chloride (KCl) for 2 h through a microdialysis probe implanted in the occipital cortex. Control animals were handled identically except that saline was infused instead of KCl. Focal ischemia was produced by the intraluminal suture method and cortical and subcortical infarct volumes were measured 7 days later. Neocortical infarct volume was reduced from 124.8 ± 49.5 mm3 in the controls to 62.9 ± 59.5 mm3 in the animals preconditioned with CSD (p = 0.012). There was no difference between the two groups in the subcortical infarct volume or in CBF, measured by the hydrogen clearance method, during or immediately after the ischemic interval. Our data indicate that preconditioning CSD applied 3 days before middle cerebral artery occlusion may increase the brain's resistance to focal ischemic damage and may be used as a model to explore the neuroprotective molecular responses of neuronal and glial cells.
40
Chen, Qun, Michael Chopp, Gordon Bodzin y Hua Chen. "Temperature Modulation of Cerebral Depolarization during Focal Cerebral Ischemia in Rats: Correlation with Ischemic Injury". Journal of Cerebral Blood Flow & Metabolism 13, n.º 3 (mayo de 1993): 389–94. http://dx.doi.org/10.1038/jcbfm.1993.52.
Resumen
The role of cerebral depolarizations in focal cerebral ischemia is unknown. We therefore measured the direct current (DC) electrical activity in the cortex of Wistar rats subjected to transient occlusion of the middle cerebral artery (MCA). Focal ischemia was induced for 90 min by insertion of an intraluminal filament to occlude the MCA. To modulate cell damage, we subjected the rats to hypothermic (30°C, n = 4), normothermic (37°C, n = 4), and hyperthermic (40°C, n = 6) ischemia. Controlled temperatures were also maintained during 1 h of reperfusion. Continuous cortical DC potential changes were measured using two active Ag–AgCl electrodes placed in the cortical lesion. Animals were killed 1 week after ischemia. The brains were sectioned and stained with hematoxylin and eosin, for evaluation of neuronal damage, and calculation of infarct volume. All animals exhibited an initial depolarization within 30 min of ischemia, followed by a single depolarization event in hypothermic animals, and multiple periodic depolarization events in both normothermic and hyperthermic animals. Hyperthermic animals exhibited significantly more (p < 0.05) DC potential deflections (n = 6.17 ± 0.67) than normothermic animals (n = 2.75 ± 0.96). The ischemic infarct volume (% of hemisphere) was significantly different for the various groups; hypothermic animals exhibited no measurable infarct volume, while the ischemic infarct volume was 10.2 ± 12.3% in normothermic animals and 36.5 ± 3.4% in hyperthermic animals (p < 0.05). A significant correlation was detected between the volume of infarct and number of depolarization events ( r = 0.90, p < 0.001). Our data indicate that body temperature has a profound effect on the number of ischemic depolarization events, and ischemic cell damage after transient MCA occlusion, and suggest a role for ischemic depolarizations in mediating ischemic cell damage.
41
Gisselsson, Lars, Maj-Lis Smith y Bo K. Siesjö. "Hyperglycemia and Focal Brain Ischemia". Journal of Cerebral Blood Flow & Metabolism 19, n.º 3 (marzo de 1999): 288–97. http://dx.doi.org/10.1097/00004647-199903000-00007.
Resumen
The influence of hyperglycemic ischemia on tissue damage and cerebral blood flow was studied in rats subjected to short-lasting transient middle cerebral artery (MCA) occlusion. Rats were made hyperglycemic by intravenous infusion of glucose to a blood glucose level of about 20 mmol/L, and MCA occlusion was performed with the intraluminar filament technique for 15, 30, or 60 minutes, followed by 7 days of recovery. Normoglycemic animals received saline infusion. Perfusion-fixed brains were examined microscopically, and the volumes of selective neuronal necrosis and infarctions were calculated. Cerebral blood flow was measured autoradiographically at the end of 30 minutes of MCA occlusion and after 1 hour of recirculation in normoglycemic and hyperglycemic animals. In two additional groups with 30 minutes of MCA occlusion, CO2 was added to the inhaled gases to create a similar tissue acidosis as in hyperglycemic animals. In one group CBF was measured, and the second group was examined for tissue damage after 7 days. Fifteen and 30 minutes of MCA occlusion in combination with hyperglycemia produced larger infarcts and smaller amounts of selective neuronal necrosis than in rats with normal blood glucose levels, a significant difference in the total volume of ischemic damage being found after 30 minutes of MCA occlusion. After 60 minutes of occlusion, when the volume of infarction was larger, only minor differences between normoglycemic and hyperglycemic animals were found. Hypercapnic animals showed volumes of both selective neuronal necrosis and infarction that were almost identical with those observed in normoglycemic, normocapnic animals. When local CBF was measured in the ischemic core after 30 minutes of occlusion, neither the hyperglycemic nor the hypercapnic animals were found to be significantly different from the normoglycemic group. Brief focal cerebral ischemia combined with hyperglycemia leads to larger and more severe tissue damage. Our results do not support the hypothesis that the aggravated injury is caused by any disturbances in CBF.
42
Rebel, Annette, John A. Ulatowski, Karena Joung, Enrico Bucci, Richard J. Traystman y Raymond C. Koehler. "Regional cerebral blood flow in cats with cross-linked hemoglobin transfusion during focal cerebral ischemia". American Journal of Physiology-Heart and Circulatory Physiology 282, n.º 3 (1 de marzo de 2002): H832—H841. http://dx.doi.org/10.1152/ajpheart.00880.2001.
Resumen
841, 2002. First published November 8, 2001; 10.1152/ajpheart. 00880.2001.—The beneficial effect of hemodilution on cerebral blood flow (CBF) during focal cerebral ischemia is mitigated by reduced arterial oxygen content (CaO2 ). In anesthetized cats subjected to permanent middle cerebral artery occlusion, the time course of regional CBF was evaluated after isovolemic exchange transfusion with either albumin or a tetrameric hemoglobin-based oxygen carrier. The transfusion started 30 min after arterial occlusion. We tested the hypothesis that bulk oxygen transport (CBF × CaO2 ) to ischemic tissue is increased by hemoglobin transfusion at a hematocrit of 18% compared with albumin-transfused cats at a hematocrit of 18% or control cats at a hematocrit of 30% and equivalent arterial pressure. In the nonischemic hemisphere, CBF increased selectively after albumin transfusion, and oxygen transport was similar among groups. In the ischemic cortex, albumin transfusion increased CBF, but oxygen transport was not increased above that of the control group. Hemoglobin transfusion increased both CBF and oxygen transport in the ischemic cortex above values in the control group, but the increase was delayed until 4 h of ischemia. Consequently, acute injury volume measured at 6 h of ischemia was not significantly attenuated. In contrast to the cortex, CBF in the ischemic caudate nucleus was not substantially increased by either albumin or hemoglobin transfusion. Therefore, in a large animal model of permanent focal ischemia in which transfusion starts 30 min after ischemia, tetrameric cross-linked hemoglobin transfusion can augment oxygen transport to the ischemic cortex, but the increase can be delayed and not necessarily provide protection. Moreover, an end-artery region such as the caudate nucleus is less likely to benefit from hemodilution.
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Yu, Yong-Qiang, Lian-Cheng Liu, Fa-Cai Wang, Yan Liang, Da-Qin Cha, Jing-Jing Zhang, Yu-Jun Shen, Hai-Ping Wang, Shengyun Fang y Yu-Xian Shen. "Induction Profile of MANF/ARMET by Cerebral Ischemia and its Implication for Neuron Protection". Journal of Cerebral Blood Flow & Metabolism 30, n.º 1 (23 de septiembre de 2009): 79–91. http://dx.doi.org/10.1038/jcbfm.2009.181.
Resumen
Cerebral ischemia-induced accumulation of unfolded proteins in vulnerable neurons triggers endoplasmic reticulum (ER) stress. Arginine-rich, mutated in early stage tumors (ARMET) is an ER stress-inducible protein and upregulated in the early stage of cerebral ischemia. The purposes of this study were to investigate the characteristics and implications of ARMET expression induced by focal cerebral ischemia. Focal cerebral ischemia in rats was induced by right middle cerebral artery occlusion with a suture; ischemic lesions were assessed by magnetic resonance imaging and histology; neuronal apoptosis was determined by TUNEL staining; the expressions of proteins were measured by immunohistochemistry, immunofluorescent labeling, and Western blotting. ARMET was found to be extensively upregulated in ischemic regions in a time-dependent manner. The expression of ARMET was neuronal in all examined structures in response to the ischemic insult. We also found that ARMET expression is earlier and more sensitive to ischemic stimulation than C/EBP homologous protein (CHOP). ER stress agent tunicamycin induced ARMET and CHOP expressions in the primary cultured neurons. Treatment with recombinant human ARMET promoted neuron proliferation and prevented from neuron apoptosis induced by tunicamycin. These results suggest that cerebral ischemia-induced ARMET expression may be protective to the neurons.
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Zhang, Zhenggang, Michael Chopp, Rui Lan Zhang y Anton Goussev. "A Mouse Model of Embolic Focal Cerebral Ischemia". Journal of Cerebral Blood Flow & Metabolism 17, n.º 10 (octubre de 1997): 1081–88. http://dx.doi.org/10.1097/00004647-199710000-00010.
Resumen
We developed a mouse model of embolic focal cerebral ischemia, in which a fibrin-rich clot was placed at the origin of the middle cerebral artery (MCA) in C57BL/6J mice (n = 31) and B6C3 mice (n = 10). An additional three non-embolized C57BL/6J mice were used as a control. Embolus induction, cerebral vascular perfusion deficit, and consequent ischemic cell damage were confirmed by histopathology, immunohistochemistry, laser confocal microscopy, and regional cerebral blood flow (rCBF) measurements. Reduction in rCBF and cerebral infarct were not detected in the control animals. An embolus was found in all C57BL/6J and B6C3 mice at 24 hours after injection of a clot. Regional CBF in the ipsilateral parietal cortex decreased to 23% ( P < 0.05) and 17% ( P < 0.05) of preembolization levels immediately and persisted for at least 1 hour in C57BL/6J mice (n = 6) and in B6C3 mice (n = 3), respectively. A significant decrease of rCBF was accompanied by a corresponding reduction of plasma perfusion in the ipsilateral MCA territory. Neurons exhibited marked reduction in microtubule-associated protein-2 immunostaining coincident with the area of perfusion deficit. The percent infarct volume was 30.3% ± 13.4% for C57BL/6J mice (n = 17), and 38.3% ± 15.3% for B6C3 mice (n = 7) at 24 hours after embolization. This model of embolic ischemia is relevant to thromboembolic stroke in humans and may be useful to investigate embolic cerebral ischemia in the genetically altered mouse and for evaluation of antiembolic therapies.
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Fujimoto, Motoaki, Yasushi Takagi, Tomohiro Aoki, Makoto Hayase, Takeshi Marumo, Masanori Gomi, Masaki Nishimura, Hiroharu Kataoka, Nobuo Hashimoto y Kazuhiko Nozaki. "Tissue Inhibitor of Metalloproteinases Protect Blood—Brain Barrier Disruption in Focal Cerebral Ischemia". Journal of Cerebral Blood Flow & Metabolism 28, n.º 10 (18 de junio de 2008): 1674–85. http://dx.doi.org/10.1038/jcbfm.2008.59.
Resumen
Enhanced matrix metalloproteinases (MMPs) can cause vasogenic edema and hemorrhagic transformation after cerebral ischemia, and affect the extent of ischemic injury. We hypothesized that the endogenous MMP inhibitors, tissue inhibitor of MMPs (TIMPs), were essential to protect against blood—brain barrier (BBB) disruption after ischemia by regulating the activities of MMPs. We confirmed the transition of MMP-2 and MMP-9, and the TIMPs family after 30 mins of middle cerebral artery occlusion, and elucidated the function of TIMP-1 and TIMP-2 in focal ischemia, using TIMP-1−/−and TIMP-2−/− mice. TIMP-1 mRNA expression was gradually increased until 24 h after reperfusion. In TIMP-1−/− mice, MMP-9 protein expression and gelatinolytic activity were significantly more augmented after cerebral ischemia than those in WT mice, and were accompanied by exacerbated BBB disruption, neuronal apoptosis, and ischemic injury. In contrast, TIMP-2 gene deletion mice exhibited no significant difference in MMP expressions and the degree of ischemic injury despite an increased Evans blue leakage. These results suggest that TIMP-1 inhibits MMP-9 activity and can play a neuroprotective role in cerebral ischemia.
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Wu, Chih-Jen, Jui-Tai Chen, Ting-Lin Yen, Thanasekaran Jayakumar, Duen-Suey Chou, George Hsiao y Joen-Rong Sheu. "Neuroprotection by the Traditional Chinese Medicine, Tao-Hong-Si-Wu-Tang, against Middle Cerebral Artery Occlusion-Induced Cerebral Ischemia in Rats". Evidence-Based Complementary and Alternative Medicine 2011 (2011): 1–9. http://dx.doi.org/10.1155/2011/803015.
Resumen
Tao-Hong-Si-Wu-Tang (THSWT) is a famous traditional Chinese medicine (TMC). In the present study, oral administration of THSWT (0.7 and 1.4 gkg−1day−1) for 14 days before MCAO dose-dependently attenuated focal cerebral ischemia in rats. MCAO-induced focal cerebral ischemia was associated with increases in hypoxia-inducible factor (HIF)-1α, inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-α, and active caspase-3 expressions in ischemic regions. These expressions were obviously inhibited by 0.7 gkg−1day−1THSWT treatment. In addition, THSWT inhibited platelet aggregation stimulated by collagen in washed platelets. In anin vivostudy, THSWT (16 gkg−1) significantly prolonged platelet plug formation in mice. However, THSWT (20 and 40 μgmL−1) did not significantly reduce the electron spin resonance (ESR) signal intensity of hydroxyl radical (OH•) formation. In conclusion, the most important findings of this study demonstrate for the first time that THSWT possesses potent neuroprotective activity against MCAO-induced focal cerebral ischemiain vivo. This effect may be mediated, at least in part, by the inhibition of both HIF-1αand TNF-αactivation, followed by the inhibition of inflammatory responses (i.e., iNOS expression), apoptosis formation (active caspase-3), and platelet activation, resulting in a reduction in the infarct volume in ischemia-reperfusion brain injury.
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Sharipov, Roman R., Nataliya A. Dorofeyeva y Vadim F. Sagach. "Cardiohemodynamic Changes in Focal Cerebral Ischemia". International Journal of Physiology and Pathophysiology 9, n.º 4 (2018): 335–40. http://dx.doi.org/10.1615/intjphyspathophys.v9.i4.60.
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Temiz, Cuneyt, Kagan Tun, Hasan Caglar Ugur, Robert J. Dempsey y Nihat Egemen. "L-arginine in focal cerebral ischemia". Neurological Research 25, n.º 5 (julio de 2003): 465–70. http://dx.doi.org/10.1179/016164103101201869.
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SHARIPOV, R. R., N. A. DOROFEYEVA y V. F. SAGACH. "Cardiohemodynamic changes in focal cerebral ischemia". Fiziolohichnyĭ zhurnal 64, n.º 1 (20 de febrero de 2018): 11–15. http://dx.doi.org/10.15407/fz64.01.011.
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Tasker, Robert C. y Elizabeth D. Duncan. "Focal cerebral ischemia and neurovascular protection". Current Opinion in Pediatrics 27, n.º 6 (diciembre de 2015): 694–99. http://dx.doi.org/10.1097/mop.0000000000000287.