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

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.