AJP - Regulatory, Integrative and Comparative Physiology, Vol 263, Issue 4 909-R914, Copyright © 1992 by American Physiological Society
Platelet-activating factor antagonists limit glycine changes and behavioral deficits after brain trauma
A. I. Faden and P. A. Tzendzalian
Department of Neurology, Georgetown University School of Medicine, Washington, DC 20007.
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.
