Pharmacologic strategies in the treatment of experimental brain injury.
Although the mechanisms underlying secondary or delayed damage after traumatic injury to the central nervous system (CNS) are poorly understood, delayed neuronal injury may result from pathologic changes in the brain's endogenous neurochemistry. These neurochemical changes may include the overactivation of neurotransmitter release systems, changes in presynaptic or postsynaptic receptor binding, or the pathologic release or synthesis of autodestructive injury factors. Identification of such factors and the timing of the neurochemical cascade after CNS injury provides a window of opportunity for treatment with pharmacologic agents that modify synthesis, release, receptor binding, or physiologic activity with subsequent limitation of damage and disability. Over the past decade, a number of experimental studies have reported that modification of postinjury events by pharmacologic manipulation can promote functional recovery in a variety of animal models of CNS injury. This article summarizes the recent work suggesting that endogenous opioid peptides, catecholamines, and magnesium all play a role in the pathophysiologic cascade after brain injury and that pharmacologic manipulation of these endogenous systems may improve functional outcome after brain injury.
McIntosh
T K
TK
Department of Surgery, University of Connecticut Health Center, Farmington.
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000503:physiopathology*; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002395:Catecholamines / Q000502:physiology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004723:Endorphins / Q000502:physiology / Q000627:therapeutic use*; D008274:Magnesium / Q000378:metabolism / Q000627:therapeutic use*
D002395:Catecholamines; D004723:Endorphins; D008274:Magnesium