Platelet-activating factor. A putative mediator in central nervous system injury?
Platelet-activating factor (1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphorylcholine) is a potent lipid autacoid produced by many cell types. Platelet-activating factor is produced by cerebellar granule cells in culture and has been extracted from brain tissue. Multiple platelet-activating factor receptors have been demonstrated in brain tissue. Activation of platelet-activating factor receptors in transformed neuronal cell lines involved increases in intracellular calcium. Platelet-activating factor has potent actions on cerebral vessels and cerebral metabolism when administered in vivo, but may not have direct effects on brain microvessels. Excessive platelet-activating factor production in pathological states of the nervous system such as neurotrauma and stroke has been shown in only a few models (e.g., spinal cord ischemia and reperfusion or focal repercussion brain injury). In multiple studies using highly specific and potent platelet-activating factor antagonists, reversal or prevention of key consequences of brain injury such as hypoperfusion following ischemia, reperfusion and edema, inflammatory cell accumulation, neurologic/motor deficits, and neuronal salvage were demonstrated. This review provides and analyzes evidence in support of the role that platelet-activating factor might have in modulation of brain function and pathophysiological processes in brain ischemia and trauma.
Feuerstein
G
G
Division of Pharmacology, SmithKline Beecham, Philadelphia, Pa.
Yue
T L
TL
Lysko
P G
PG
D000818:Animals; D001921:Brain / Q000098:blood supply / Q000378:metabolism*; D002561:Cerebrovascular Disorders / Q000378:metabolism*; D004224:Diterpenes; D005849:Gerbillinae; D046934:Ginkgolides; D007783:Lactones / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D015398:Signal Transduction
D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; C045856:ginkgolide B