Post-acute ischemic stroke hyperglycemia aggravates destruction of the blood-brain barrier

Author:

Xu Tianqi1,Yang Jianhong1,Xu Yao1,Wang Xiaofeng2,Gao Xiang3,Sun Jie3,Zhou Chenhui34ORCID,Huang Yi34ORCID

Affiliation:

1. Department of Neurology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang Province, China

2. Department of General Surgery, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang Province, China

3. Department of Neurosurgery, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang Province, China

4. Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province, Ningbo, Zhejiang Province, China

Abstract

Abstract JOURNAL/nrgr/04.03/01300535-202406000-00039/inline-graphic1/v/2023-10-30T152229Z/r/image-tiff Post-acute ischemic stroke hyperglycemia increases the risk of hemorrhagic transformation, which is associated with blood-brain barrier disruption. Brain microvascular endothelial cells are a major component of the blood-brain barrier. Intercellular mitochondrial transfer has emerged as a novel paradigm for repairing cells with mitochondrial dysfunction. In this study, we first investigated whether mitochondrial transfer exists between brain microvascular endothelial cells, and then investigated the effects of post-acute ischemic stroke hyperglycemia on mitochondrial transfer between brain microvascular endothelial cells. We found that healthy brain microvascular endothelial cells can transfer intact mitochondria to oxygen glucose deprivation-injured brain microvascular endothelial cells. However, post-oxygen glucose deprivation hyperglycemia hindered mitochondrial transfer and exacerbated mitochondrial dysfunction. We established an in vitro brain microvascular endothelial cell model of the blood-brain barrier. We found that post-acute ischemic stroke hyperglycemia reduced the overall energy metabolism levels of brain microvascular endothelial cells and increased permeability of the blood-brain barrier. In a clinical study, we retrospectively analyzed the relationship between post-acute ischemic stroke hyperglycemia and the severity of hemorrhagic transformation. We found that post-acute ischemic stroke hyperglycemia serves as an independent predictor of severe hemorrhagic transformation. These findings suggest that post-acute ischemic stroke hyperglycemia can aggravate disruption of the blood-brain barrier by inhibiting mitochondrial transfer.

Publisher

Medknow

Subject

Developmental Neuroscience

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