Platelet secretory products may contribute to neuronal injury.

Abstract

Background: We do not fully understand the mechanisms for neuronal damage following cerebral arterial occlusion by a thrombus that consists mainly of platelets. The view that certain endogenous substances, such as glutamate, may also contribute to neuronal injury is now reasonably well established. Blood platelets are known to contain and secrete a number of substances that have been associated with neuronal dysfunction. Therefore, we hypothesize that a high concentration (approximately several thousand-fold higher than in plasma, in our estimation) of locally released platelet secretory products derived from the causative thrombus may contribute to neuronal injury and promote reactive gliosis. Summary of Comment:We have recently been able to report some direct support for this concept. When organotypic spinal cord cultures were exposed to platelet and platelet products, a significant reduction in the number and the size of the surviving neurons occurred in comparison with those in controls. We further observed that serotonin, a major platelet product, has neurotoxic properties. There may be other platelet components with similar effect.Conclusions: The hypothesis of platelet-mediated neurotoxicity gains some support from these recent in vitro findings. The concept could provide a new area of research in stroke, both at the clinical and basic levels. (Stroke 1991;22:1448-1451)

Electrophysiological effects of 5‐hydroxytryptamine on isolated human atrial myocytes, and the influence of chronic β‐adrenoceptor blockade

“…The concentration of free 5-HT in human whole blood has been reported to range from nanomolar, rising to nearly micromolar, levels after activation of platelets (Joseph et al, 1991). The present results confirm that within this concentration range 5-HT has important electrophysiological effects on human atrial myocytes.…”

Role of activated platelets in excitation of cardiac afferents during myocardial ischemia in cats

“…Strong agonists such as collagen, thrombin, the calcium ionophore A-23187, and phorbol esters can induce secretion of granules, a procedure independent of arachidonic acid metabolites (14,31,37). Concentration of free 5-HT in human whole blood increases from 36 to 836 nM after activation of platelets with collagen (16). Adding thrombin to PRP stimulates platelets to release 5-HT (2).…”

Characterization of a thromboembolic photochemical model of repeated stroke in mice

“…Also, previous studies on acute blood-brain barrier (BBB) consequences following MCA photothrombosis suggested that endothelial-platelet interactions at the vascular site of injury are responsible for the release of neurohumoral factors which contribute to the acute opening of the BBB . Therefore, this model features the important role that platelets and their secretory products may have in contributing to neuronal injury via thromboembolism (Joseph et al, 1991). On the other hand, in a recent clinical study, histological examination of thrombo-and atheroemboli retrieved from the MCA or intracranial internal carotid artery of patients with acute ischemic stroke showed that no two such emboli were similar in overall appearance, but demonstrated a distinctive pattern, comprised of layers of "serpentine" fibrin/platelet bands interspersed with accumulations of trapped erythrocytes (Marder et al, 2006).…”