Academic literature on the topic 'Anoxia. Neuropeptide Y. Norepinephrine'

Significant advances in our understanding of the neurobiology of pain in osteoarthritis (OA) have occurred in the last decade and are herein summarized. Pain is the predominant symptom of OA and occurs at multiple levels from non-cartilage peripheral tissues to spinal cord, and brain and back. At each level, nerve function is regulated by complex ionic channels, neuropeptide expression, and cytokine and chemokine activity. Previously considered a non-inflammatory condition, it is now recognized that cell proliferation and inflammatory cytokine production occurs in OA synovium, contributing to

Sleep is required for health and well-being, and consumes roughly one-third of a human’s lifetime, yet its functions remain incompletely understood. This chapter provides an overview of so-called sleep architecture—the stages and cycles that characterize sleep, including rapid eye movement (REM) and non-REM periods. Also discussed are the numerous regions of brain and neurotransmitters that control the induction of sleep, the transitions between REM and non-REM sleep cycles, and wakefulness. Key brain systems include GABAergic neurons in the pre-optic area, the neuropeptide orexin in lateral h

Stimulants are typically prescribed for their positive effects on mood, motivation, alertness, arousal, and energy. They are believed to exert their pharmacologic effects by increasing synaptic release of endogenous catecholamines (norepinephrine and dopamine) while simultaneously blocking catecholamine reuptake at the nerve terminals. Themost commonly used ‘‘traditional’’ agents are methylphenidate and dextroamphetamine. Methylphenidate reaches peak blood levels in 1 to 3 hours and has an elimination half-life of 2 to 3 hours. Dextroamphetamine reaches peak levels in 2 to 4 hours and has an elimination half-life of 3 to 6 hours. Controlled-release formulations are available, allowing for dosing once daily. Dextroamphetamine is excreted primarily in the urine in unchanged form, whereas methylphenidate is excreted mainly as ritalinic acid. The newer generation stimulant modafinil has been marketed in the United States since 1998. Initially used in the treatment of narcolepsy, it is now prescribed for a wider range of conditions because of its positive effects on wakefulness, vigilance, cognitive performance, and mood. Its pharmacologic effects are thought to result primarily from the stimulation of wakefulness-promoting orexinergic neurons in the anterior hypothalamus. Inhibition of norepinephrine reuptake in the ventrolateral preoptic nucleus and of dopamine reuptake (by binding to the transporter) may contribute to its action. Modafinil is administered orally, achieves peak plasma concentrations in 2 to 4 hours, and has an elimination half-life of 12 to 15 hours. It is 90% metabolized in the liver, and its metabolites are excreted in the urine. The ergot alkaloids bromocriptine and pergolide are familiar to most neurologists in their use in the treatment of Parkinson’s disease (PD) and migraine headache. These dopamine receptor agonists are also used in neuropsychiatry in the treatment of apathetic states in patients recovering from brain trauma, cerebral anoxia, and strokes. Amantadine is another familiar agent used in the treatment of PD and drug-induced parkinsonism. In addition to other effects in the central nervous system (CNS), amantadine facilitates dopamine release and inhibits its reuptake. It thus has modest ‘‘stimulant-like’’ effects useful in the treatment of executive dysfunction syndromes, particularly in patients with dementia. Bupropion is a dopamine and norepinephrine reuptake inhibitor. It usually is prescribed as a ‘‘nonsedating’’ antidepressant, but its potentiation of catecholamine neurotransmission results in modest stimulant-like clinical effects.

As part of the biological rhythm, the human brain has a healthy functioning with the ability to differentiate between day and night hours in any given day (sleep rhythm, life rhythm). From the control of hormone levels to muscle tonus, from the regulation of respiratory rate to the content of our thoughts, sleep has an impact on all bodily and cognitive functions. It is not surprising to see such effects of sleep on the body as it leads to significant changes in the electrical activity of the brain in general. Electrical signal changes in the brain (sleep-wakefulness rhythm) are regulated by neurohormonal molecules and their receptors in the body. Neurotransmitters that control sleep and wakefulness can be listed as “Glutamate, Acetylcholine, Histamine, Norepinephrine and GABA”. Main hormones are: Melatonin, Corticotropin Releasing Hormone (CRH), cortisol, prolactin, Growth Hormone (GH), Insulin like Growth Factor (IGF-1, Somatomedin-C), Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH), progesterone, estrogen, testosterone, catecholamines, leptin and neuropeptide Y″. The effects of pharmacological agents on sleep and wakefulness cycles are materialized through the following molecules and their receptors: Hypnotics (GABA A agonists, benzodiazepines, gabapentin, tiagabine), sedative antidepressants (tricyclic antidepressants, trazadone, mitrazapine), antihistamines, medications used for the treatment of sleeplessness (melatonin and melatonin analogues), amphetamine (most commonly used stimulant), secretion of monoamines (dopamine), non-amphetamine stimulants used in the treatment of hypersomnia and narcolepsy (modafinil, bupropion, selegiline, caffeine) and other substances (alcohol, nicotine, anesthetics). To the extent we can conceptualize the physiological mechanisms of these basic molecules listed above and the regions they affect, we can appreciate the effects of these substances on sleep physiology and sleep disorders.

While multiple hormones influence somatic growth, the main regulator of postnatal growth is growth hormone. Growth hormone (GH) is secreted in a pulsatile manner from the anterior pituitary primarily as a 22-kilodalton molecule (although other forms may be found). The development of the pituitary gland as well as GH gene expression is regulated by the multiple pituitary transcription factors listed in Table11-1. The Pit-1 and Prop-1 genes encode proteins that are often mutated or deleted in cases of congenital hypopituitarism. Under normal waking conditions, GH levels are often low or undetectable, but several times during the day, and particularly at night during stage 3 of sleep, surges of GH secretion occur. The pulsatile pattern characteristic of GH secretion largely reflects the interaction of multiple regulators, including two hypothalamic regulatory peptides: GH-releasing hormone (GHRH), which stimulates GH secretion, and somatostatin (somatotropin release–inhibiting factor [SRIF]), which inhibits GH secretion. Multiple neurotransmitters and neuropeptides are involved in regulation of release of these hypothalamic factors, including, but not limited to, serotonin, histamine, norepinephrine, dopamine, acetylcholine, γ -aminobutyric acid (GABA), thyroid-releasing hormone, vasoactive intestinal peptide, gastrin, neurotensin, substance P, calcitonin, neuropeptide Y, vasopressin, corticotropinreleasing hormone, and galanin. Many factors influence GH secretion; notably, glucose that inhibits, and certain amino acids and Ghrelin that stimulate GH secretion. GH secretion is also impacted by a variety of nonpeptide hormones, including androgens, estrogens, thyroxine, and glucocorticoids. The precise mechanisms by which these hormones regulate GH secretion are complex, potentially involving actions at both the hypothalamic and pituitary levels. Exogenous physiological and pharmacological factors are known to stimulate GH secretion. Some of these agents, including clonidine, L-dopa, and exercise, are used in GH stimulation tests. In plasma, the majority of GH is bound with high specificity and affinity, but with relatively low capacity to a carrier protein termed GH binding protein (GHBP). The GHBP is a cleavage product of the extracellular domain of the GH receptor.