The Role of Oxidative Stress in Microvascular Disturbances after Experimental Subarachnoid Hemorrhage

Abstract

Oxidative stress was shown to play a crucial role in the diverse pathogenesis of early brain injury (EBI) after subarachnoid hemorrhage (SAH). Microcirculatory dysfunction is thought to be an important and fundamental pathological change in EBI. However, other than blood-brain barrier (BBB) disruption, the influence of oxidative stress on microvessels remains to be elucidated. The aim of this study was to investigate the role of oxidative stress on microcirculatory integrity in EBI. SAH was induced in male Sprague-Dawley rats using an endovascular perforation technique. A free radical scavenger, edaravone, was administered prophylactically by intraperitoneal injection. SAH grade, neurological score, brain water content, and BBB permeability were measured at 24 h after SAH induction. In addition, cortical samples taken at 24 h after SAH were analyzed to explore oxidative stress, microvascular mural cell apoptosis, microspasm, and microthrombosis. Edaravone treatment significantly ameliorated neurological deficits, brain edema, and BBB disruption. In addition, oxidative stress-induced modifications and subsequent apoptosis of microvascular endothelial cells and pericytes increased after SAH induction, while the administration of edaravone suppressed this. Consistent with apoptotic cell inhibition, microthromboses were also inhibited by edaravone administration. Oxidative stress plays a pivotal role in the induction of multiple pathological changes in microvessels in EBI. Antioxidants are potential candidates for the treatment of microvascular disturbances after SAH.

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Acknowledgements

The authors thank Mark Inglin (University of Basel) for his editorial assistance.

Funding

This study was supported partially by JSPS KAKENHI Grant Number JP16K19993 (to MN).

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Correspondence to Hiroki Ohkuma.

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Fumoto, T., Naraoka, M., Katagai, T. et al. The Role of Oxidative Stress in Microvascular Disturbances after Experimental Subarachnoid Hemorrhage. Transl. Stroke Res. 10, 684–694 (2019). https://doi.org/10.1007/s12975-018-0685-0

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Keywords

  • Early brain injury
  • Subarachnoid hemorrhage
  • Oxidative stress
  • Microvessel