Faculty, Staff and Student Publications

Publication Date

4-1-2026

Journal

Experimental & Molecular Medicine

DOI

10.1038/s12276-026-01696-1

PMID

41986479

Abstract

After subarachnoid hemorrhage (SAH), some patients develop delayed neurological deficits (DND). Microthrombi are considered a contributing factor to DND, but clinical trials of antiplatelets had mixed results. Existing research suggests that platelets play a role in the etiology of DND, but no comprehensive study has tested causality between platelets and DND after SAH. Here we hypothesize that after SAH, platelet activation promotes microthrombi formation, occlusion of the brain microvasculature and contributes to DND, and that inhibiting platelet aggregation is a therapeutic strategy. Mice experiencing SAH were administered various interventions. The animals were subjected to stimulation of platelets, platelet depletion, or antiplatelet drugs and then underwent daily neurological assessment until day 7 before euthanasia for brain microthrombi counting. In parallel, platelets isolated from blood of patients with aneurysmal SAH were tested with antiplatelets to determine how they effected platelet activation. In mice, SAH caused increased levels of platelet-activating factors and more cerebrovascular microthrombi, which correlated with DND. Exogenous platelet activation caused worse outcomes and DND, whereas platelet depletion reduced microthrombi, leading to improved outcomes and a lower incidence of DND. Selected antiplatelet drugs improved outcomes on days 1 and 2 (sex-specific benefits were observed) and one antagonist reduced DND incidence. In platelets from human patients with SAH, antagonism can also prevent platelet activation. After SAH, platelets lead to brain microthrombi and DND, suggesting that platelets are a therapeutic target. Platelet depletion and antagonism can prevent microthrombi and DND in mice. This study serves as a preclinical proof-of-concept that platelets may represent a therapeutic target for SAH.

Keywords

Animals, Subarachnoid Hemorrhage, Mice, Blood Platelets, Humans, Male, Platelet Activation, Disease Models, Animal, Platelet Aggregation Inhibitors, Microvessels, Nervous System Diseases, Female, Mice, Inbred C57BL

Published Open-Access

yes

Download

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.