Title:Microthrombosis at the Ultra-early Stages after Experimental Subarachnoid Hemorrhage Results in Early Brain Injury
Volume: 21
Issue: 5
Author(s): Masaki Kumagai, Yusuke Egashira, Nozomi Sasaki, Shinsuke Nakamura, Yoshiki Kuse, Hirohumi Matsubara, Yukiko Enomoto, Tsuyoshi Izumo, Hideaki Hara and Masamitsu Shimazawa*
Affiliation:
- Molecular Pharmacology,
Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan
- Laboratory of Collaborative
Research for Innovative Drug Discovery, Gifu Pharmaceutical University, Gifu, Japan
Keywords:
Subarachnoid hemorrhage, early brain injury, cerebral blood flow, microthrombosis, thrombin, matrix metalloproteinase-9, neuroinflammation.
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.
