Platelet-activating factor in stroke and brain injury.
Platelet-activating factor, an endogenous phospholipid of proinflammatory, hemostatic, and vasoactive properties, is synthesized by neurons and in injured brain. Platelet-activating factor is released together with eicosanoids such as thromboxane A2, prostacyclin, and leukotrienes. Its effects in neurons are mediated through a specific receptor coupled to phospholipase C and phosphoinositol metabolism. The cerebrovascular effects of platelet-activating factor include disruption of the blood-brain barrier, edema formation, and vasospasm. It has also been described to possess direct toxicity to neuronal cells in culture. Discovery and development of several highly potent and selective antagonists to platelet-activating factor receptors facilitated experimental studies underscoring the role of this factor as an endogenous mediator in cerebral disorders, particularly cerebral ischemia and trauma. Significant biochemical, microvascular, functional, and behavioral recovery has been demonstrated using these antagonists in an array of experimental models of focal and global ischemia in the central nervous system (CNS). Clearly, studies of platelet-activating factor in experimental models of CNS ischemia and reperfusion injury open a new perspective on phospholipid metabolism in stroke and offer an exceptionally promising therapeutic prospect. Data supporting this factor as a mediator of specific pathological sequelae in stroke and neuroinjury are surveyed in this review. We discuss the mechanisms and significance of platelet-activating factor-mediated effects and propose directions for future studies.
Lindsberg
P J
PJ
Department of Neurology, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD.
Hallenbeck
J M
JM
Feuerstein
G
G
D000818:Animals; D001930:Brain Injuries / Q000503:physiopathology*; D002545:Brain Ischemia / Q000503:physiopathology*; D006801:Humans; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*
D010972:Platelet Activating Factor