Study of platelet-mediated neurotoxicity in rat brain.

Abstract

The mechanism of ischemic neuronal injury is not fully resolved. The present view is that vascular occlusion per se does not fully account for the extent of neurological dysfunction. We previously hypothesized that platelet secretory products might contribute to neuronal injury in the central nervous system. Our preliminary studies using organotypic rat spinal cord cultures exposed to human platelet and its secretory products revealed that platelet products had neurotoxic properties. Further studies, using the same methods, were conducted, with the addition of several refinements such as use of gel-filtered platelets (as opposed to washed platelets) and adding additional relevant controls including platelet membranes, red blood cells, and washed rat platelets. Exposure of spinal cord explant cultures to platelet secretory products resulted in reduced number of neurons per ventral horn compared with control. Our findings suggest that platelet secretory products have neurotoxic properties. This effect was seen with platelet secretion obtained from physiological platelet concentrations. It appears possible that more abundant release of platelet products at the site of thrombus formation could have pathological significance in vivo.