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Characteristics of Cerebrovascular Injury in the Hyperacute Phase After Induced Severe Subarachnoid Hemorrhage

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Abstract

Although there have been several investigations regarding acute brain injury after subarachnoid hemorrhage (SAH), the pathological conditions of severe SAH are unclear. In this study, we pursued the characteristics of cerebrovascular injury in the hyperacute phase after experimentally induced severe SAH. Twenty-three male Sprague-Dawley rats were subjected to sham or SAH operation using the endovascular perforation method and were evaluated for brain edema, blood-brain barrier (BBB) permeability, and arterial endothelial cell injury at 5 min after SAH (experiment 1). Next, animals were examined for functional and morphological changes of cerebral artery for 30 min after an acetazolamide injection administered 5 min after SAH (experiment 2). In experiment 1, while cerebral blood flow (CBF) was reduced, brain edema was not observed in SAH-operated rats. BBB permeability detected by immunoglobulin G extravasation was observed in the optic tract and was accompanied by the upregulation of phosphorylated extracellular signal-regulated kinase (ERK)-positive astrocytes. In addition, the number of phosphorylated ERK-positive endothelial cell in the distal middle cerebral artery (MCA) was significantly increased by SAH. In experiment 2, CBF in non-lethal SAH rats was reduced, and no response to acetazolamide was detected. Conversely, CBF in lethal SAH increased due to acetazolamide, although the value of CBF was low. Furthermore, there was significant narrowing of the MCA in SAH-operated rats. The findings suggest that the optic tract and the cerebral artery are the most vulnerable areas regarding cerebrovascular injury in a hyperacute phase after severe SAH and that they are associated with fatal outcomes.

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Acknowledgments

This study was supported by JSPS KAKENHI Grant Number 24592135. We thank Yuriko Shimamura, Miho Kataoka, Michie Uchikawa, and Keiko Morozumi for their support.

Compliance with Ethics Requirements

All institutional and national guidelines for the care and use of laboratory animals were followed.

Conflict of Interest

The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Department of Pharmacology and Molecular Therapeutics, Graduate School of Medical Sciences, Kumamoto University, 1-1-1, Honjo, Chuo-ku, Kumamoto-shi, Kumamoto-ken, 8608556, Japan

    Yu Hasegawa, Ken Uekawa & Shokei Kim-Mitsuyama

  2. Department of Neurosurgery, Mie University Graduate School of Medicine, 2-174, Edobashi, Tsu-shi, Mie-ken, 5148507, Japan

    Hidenori Suzuki

  3. Department of Neurosurgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1, Honjo, Chuo-ku, Kumamoto-shi, Kumamoto-ken, 8608556, Japan

    Takayuki Kawano

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  1. Yu Hasegawa
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  2. Hidenori Suzuki
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  5. Shokei Kim-Mitsuyama
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Correspondence to Yu Hasegawa.

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Hasegawa, Y., Suzuki, H., Uekawa, K. et al. Characteristics of Cerebrovascular Injury in the Hyperacute Phase After Induced Severe Subarachnoid Hemorrhage. Transl. Stroke Res. 6, 458–466 (2015). https://doi.org/10.1007/s12975-015-0423-9

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  • DOI: https://doi.org/10.1007/s12975-015-0423-9

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