Platelet-activating factor--key mediator in neuroinjury?
A growing body of evidence supports the hypothesis that platelet-activating factor (PAF) may be a key mediator in neuroinjury. PAF, originally isolated from stimulated basophils, can be produced by a variety of cells, such as polymorphonuclear leukocytes (PMNLs), platelets, monocytes, macrophages, and endothelial cells and has been suggested as a mediator of inflammation, platelet and neutrophil activation, plasma extravasation, and anaphylactic shock. Enhanced phospholipid metabolism in the ischemic penumbral zone has been reported and provides opportunity for production of PAF. A possible involvement of this lipid mediator in processes associated with cerebral ischemia and neurotrauma has been suggested by an increasing number of reports. PAF exerts cytotoxic effects on neuronal cells, causes vasoconstriction, and increases the blood-brain barrier permeability. Beneficial effects of PAF antagonists have been shown in various models of cerebral ischemia: pre- as well as postischemic application of the PAF antagonist resulted in reduction of edema and improved neurological outcome and improved cerebral microcirculation. These effects were correlated with improved neuronal survival and reduced accumulation of PMNLs, supporting a link and positive feedback between PAF and PMNLs in these processes. Since PAF appears to be uniquely involved in various pathophysiological events, it may function as a key mediator in ischemic and traumatic neuroinjury. The current review summarizes the current understanding of the function and biochemistry of PAF with respect to CNS physiology and pathology.
Frerichs
K U
KU
Department of Neurology, F. Edward Hérbert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814.
Feuerstein
G Z
GZ
D001921:Brain / Q000378:metabolism / Q000502:physiology*; D002493:Central Nervous System Diseases / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D010972:Platelet Activating Factor / Q000378:metabolism / Q000502:physiology*
D010972:Platelet Activating Factor