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Current Neurovascular Research

Editor-in-Chief

ISSN (Print): 1567-2026
ISSN (Online): 1875-5739

Research Article

Microthrombosis at the Ultra-early Stages after Experimental Subarachnoid Hemorrhage Results in Early Brain Injury

In Press, (this is not the final "Version of Record"). Available online 26 December, 2024
Author(s): Masaki Kumagai, Yusuke Egashira, Nozomi Sasaki, Shinsuke Nakamura, Yoshiki Kuse, Hirohumi Matsubara, Yukiko Enomoto, Tsuyoshi Izumo, Hideaki Hara and Masamitsu Shimazawa*
Published on: 26 December, 2024

DOI: 10.2174/0115672026362878241220065541

Price: $95

Abstract

Introduction: Early Brain Injury (EBI) significantly contributes to poor neurological outcomes and death following subarachnoid hemorrhage (SAH). The mechanisms underlying EBI post-SAH remain unclear. This study explores the relationship between serial cerebral blood flow (CBF) changes and neurological symptoms, as well as the mechanisms driving CBF changes in the ultra-early stages after experimental SAH in mice.

Methods: SAH was induced by endovascular perforation in male ddY mice. Mice were sacrificed at 6, 12, 24, and 48 h after behavioral tests using the modified neurological score and grid walking test, and CBF was measured via Laser Speckle Flow Imaging (LSFI). Neurofunctional evaluation, CBF analysis, and Western blotting were used to assess SAH-induced damage.

Results: Neurological symptoms were significantly worse at 12 h post-SAH compared to sham (9.5 ± 1.7 vs. 25.6 ± 0.63, respectively; p < 0.0001). CBF was significantly reduced at 12 h post- SAH compared to sham (35.34 ± 8.611 vs. 91.06 ± 12.45, respectively; p < 0.0001). Western blotting revealed significantly elevated thrombin and matrix metalloproteinase 9 levels 12 h post-SAH (p < 0.05).

Conclusion: Our results suggest that microthrombus formation peaked at 12 h post-SAH, potentially causing EBI and worsening neurological symptoms. Microthrombus formation in the ultraearly stages may represent a novel therapeutic target for managing EBI.

Keywords: Subarachnoid hemorrhage, early brain injury, cerebral blood flow, microthrombosis, thrombin, matrix metalloproteinase-9 (mmp9), neuroinflammation.


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