Antagonists of excitatory amino acids and endogenous opioid peptides in the treatment of experimental central nervous system injury.
Trauma to the central nervous system can lead to primary injuries occurring at the time of impact as well as secondary or delayed injury processes that can result from cellular hypoxia, oligemia/ischemia, edema and swelling, and intracranial hypertension that are manifested over a period of hours to weeks after the initial event. Although the mechanisms underlying delayed tissue injury are poorly understood, they appear to be associated with endogenous neurochemical changes resulting from traumatic nervous system injury. These neurochemical changes may include excessive neurotransmitter release, deregulation of ion homeostasis, and the synthesis, release, or activation of various "autodestructive" neurochemical factors. Experimental studies over the past decade indicate that these alterations mediate important components of the neurochemical cascade leading to central nervous system injury. Furthermore, pharmacologic manipulations of these neurochemical changes have been reported to attenuate secondary central nervous system damage, ameliorate neuronal death, and promote functional recovery after central nervous system injury. This article focuses on the role of excitatory amino acid neurotransmitters, endogenous opioid peptides, and magnesium in the pathophysiology of central nervous system injury and on the therapeutic manipulation of these systems to improve functional outcome after central nervous system injury.
Gentile
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Department of Surgery, University of Connecticut School of Medicine, Farmington.
McIntosh
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D000596:Amino Acids / Q000037:antagonists & inhibitors*; D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy*; D004723:Endorphins / Q000037:antagonists & inhibitors*; D006801:Humans; D018377:Neurotransmitter Agents / Q000037:antagonists & inhibitors*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013119:Spinal Cord Injuries / Q000188:drug therapy*
D000596:Amino Acids; D004723:Endorphins; D018377:Neurotransmitter Agents; D016194:Receptors, N-Methyl-D-Aspartate