Further studies on platelet-mediated neurotoxicity.
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 hypothesized that platelet secretory products might contribute to ischemic neuronal injury in the central nervous system (CNS) (Joseph et al., Stroke, 20 (1989) 38-44 and 1316-1319). Our preliminary studies using organotypic rat spinal cord cultures exposed to human platelet and its secretory products, revealed that platelet product(s) had neurotoxicity. Further studies, using the same methods, were conducted here, with the addition of several refinements such as use of gel-filtered platelets (as opposed to washed platelets), adding additional relevant controls including platelet membranes, red blood cells and washed rat platelets. The results confirmed our initial finding that an agent(s) in platelet secretion is neurotoxic. Subsequently, we identified serotonin (5HT), a major platelet product, as having toxic effects on neurons. This toxicity of 5HT appeared to be blocked by ketanserin, a 5HT2 receptor antagonist. Judging by the concentrations of 5HT that demonstrated neurotoxicity in these in vitro studies, it appears that products secreted from activated platelets could have pathological significance in vivo.
Joseph
R
R
Department of Neurology, Henry Ford Hospital and Health Sciences Center, Detroit, MI 48202.
Tsering
C
C
Grunfeld
S
S
Welch
K M
KM
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002462:Cell Membrane / Q000502:physiology; D002850:Chromatography, Gel; D003094:Collagen / Q000494:pharmacology; D004912:Erythrocytes / Q000502:physiology; D006897:Hydroxyindoleacetic Acid / Q000032:analysis; D007650:Ketanserin / Q000494:pharmacology; D009924:Organ Culture Techniques; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000032:analysis / Q000502:physiology; D013116:Spinal Cord / Q000502:physiology*; D013917:Thrombin / Q000494:pharmacology
D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D003094:Collagen; D007650:Ketanserin; D013917:Thrombin