Platelet-activating factor antagonists limit glycine changes and behavioral deficits after brain trauma.
Tissue damage after traumatic brain injury (TBI) results in part from delayed biochemical changes initiated by the insult. Platelet-activating factor (PAF) is an alkylphospholipid that has been implicated in tissue damage after cerebral ischemia. PAF is toxic to certain neuronal cell lines in culture, reduces cerebral blood flow, alters the blood-brain barrier, and can enhance phospholipid hydrolysis. The recent development of receptor antagonists to PAF permits examination of its possible role in delayed tissue injury after neurotrauma. Treatment with the PAF receptor antagonists BN 52021 and WEB 2170 before injury significantly enhanced neurological recovery after fluid percussion-induced TBI in rats. Pretreatment with WEB 2170 also significantly limited alterations in tissue water content and tissue glycine levels after trauma, and reduced posttraumatic levels of extracellular glycine in ipsilateral hippocampus. These findings implicate PAF in the pathophysiology of TBI, through actions at PAF receptors. A possible role for glycine in this process is suggested.
Faden
A I
AI
Department of Neurology, Georgetown University School of Medicine, Washington, DC 20007.
Tzendzalian
P A
PA
D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D001522:Behavior, Animal / Q000502:physiology*; D001834:Body Water / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D001930:Brain Injuries / Q000378:metabolism* / Q000523:psychology; D002412:Cations / Q000378:metabolism; D003956:Dialysis / Q000379:methods; D004224:Diterpenes; D046934:Ginkgolides; D005998:Glycine / Q000378:metabolism*; D007783:Lactones / Q000494:pharmacology*; D008297:Male; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014230:Triazoles / Q000494:pharmacology*
D001381:Azepines; D002412:Cations; D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; D014230:Triazoles; C063964:bepafant; C045856:ginkgolide B; D005998:Glycine