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Role of Glibenclamide in Brain Injury After Intracerebral Hemorrhage

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Abstract

Brain edema following intracerebral hemorrhage (ICH) causes severe secondary brain injury, and no efficient pharmacological preventions are available. The present study was designed to demonstrate the neuroprotective effects of glibenclamide on brain edema and key factors of the blood–brain barrier (BBB). The study was divided into two parts. First, we utilized an autoblood-induced rat model to investigate the expression of sulfonylurea receptor 1 (Sur1). Second, rats were randomized into sham, vehicle, and glibenclamide groups. Neurological scores, brain water content, Evans blue extravasation, Morris water maze test, western blots, and immunofluorescence were used to study the effects of glibenclamide. The expression of the Sur1-Trpm4 channel but not the Sur1-KATP channel was increased in the perihematomal tissue following ICH. Glibenclamide administration significantly decreased the brain water content, restored the BBB, and reduced the expression of MMPs. In addition, glibenclamide improved long-term cognitive deficits following ICH. Glibenclamide protected BBB integrity and improved neurological outcomes after ICH by inhibiting the Sur1-Trpm4 channel, which reduces the expression of MMPs and thereby increases BBB tight-junction protein levels. Glibenclamide may have potential to protect the BBB after ICH.

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Authors and Affiliations

  1. Department of Neurosurgery, Southwest Hospital, Third Military Medical University, No. 30, Gaotanyan Street, Chongqing, 400038, People’s Republic of China

    Bing Jiang, Qianwei Chen, Yihao Tao, Liming Yang, Bo Zhang, Hua Feng, Zhi Chen, Jun Tang & Gang Zhu

  2. Department of Neurosurgery, Nanchong Central Hospital, Sichuan, 637000, China

    Lin Li

  3. Department of Neurosurgery, School of Medicine, Loma Linda University, Loma Linda, CA, USA

    John H. Zhang

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  1. Bing Jiang
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  2. Lin Li
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  10. Jun Tang
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  11. Gang Zhu
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Correspondence to Jun Tang or Gang Zhu.

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

Sources of Funding

This work was supported by the National Natural Science Foundation of China (grant no. 81571130; no. 81571116; no. 81601356) and the National ‘973’ Project of China (no. 2014CB541605).

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The authors declare that they have no conflicts of interest.

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Jiang, B., Li, L., Chen, Q. et al. Role of Glibenclamide in Brain Injury After Intracerebral Hemorrhage. Transl. Stroke Res. 8, 183–193 (2017). https://doi.org/10.1007/s12975-016-0506-2

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