中国神经再生研究(英文版) ›› 2024, Vol. 19 ›› Issue (6): 1344-1350.doi: 10.4103/1673-5374.385851

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

急性缺血性脑卒中后应激性高血糖可加剧血脑屏障损伤

  

  • 出版日期:2024-06-15 发布日期:2023-11-18
  • 基金资助:
    宁波市公益性科技计划项目(2022S023),宁波市自然科学基金项目(2022J211),宁波医药卫生品牌学科(PPXK2018-04),浙江省动脉粥样硬化疾病精准医学重点实验室项目(2022E10026)

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

Tianqi Xu1, #, Jianhong Yang1, #, Yao Xu1, Xiaofeng Wang2, Xiang Gao3, Jie Sun3, Chenhui Zhou3, 4, *, Yi Huang3, 4, *   

  1. 1Department of Neurology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang Province, China; 2Department of General Surgery, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang Province, China; 3Department of Neurosurgery, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang Province, China; 4Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province, Ningbo, Zhejiang Province, China
  • Online:2024-06-15 Published:2023-11-18
  • Contact: Chenhui Zhou, MD, fyyzhouchenhui@nbu.edu.cn; Yi Huang, PhD, huangy102@gmail.com.
  • Supported by:
    This study was supported by the Ningbo Public Welfare Science and Technology Program, No. 2022S023 (to JY), Ningbo Natural Science Foundation, No. 2022J211 (to JS), Ningbo Medical and Health Brand Discipline, No. PPXK2018-04 (to XG), Ningbo Top Medical and Health Research Program, No. 2022020304 (to XG), and Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province, No. 2022E10026 (to YH).

摘要:

急性缺血性脑卒中后应激性血糖升高是脑出血转化的危险因素,且脑出血性转化与血脑屏障破坏有关。脑微血管内皮细胞是血脑屏障的主要成分,其细胞间线粒体转移已成为修复线粒体功能障碍细胞的一种新范式。因此实验首先观察了脑微血管内皮细胞之间是否存在线粒体转移现象,随后探究了氧糖剥夺损伤以及其后的高糖刺激对脑微血管内皮细胞间线粒体转移程度的影响。结果发现,健康的脑微血管内皮细胞可将自身完整的线粒体转移至氧糖剥夺损伤的脑微血管内皮细胞,而氧糖剥夺损伤后的高糖刺激能够抑制脑微血管内皮细胞间的线粒体转移程度,并破坏线粒体功能。紧接着以脑微血管内皮细胞建立了血脑屏障体外模型,可见氧糖剥夺后应激性高血糖能够降低脑微血管内皮细胞的总体能量代谢水平,并增加血脑屏障通透性。进一步通过临床研究,回顾性分析了缺血性脑卒中后高血糖与脑出血转化严重程度之间的关系,发现急性缺血性脑卒中后应激性高血糖是重度脑出血转化的独立预测因子。提示急性缺血性脑卒中后应激性高血糖可加重血脑屏障破坏,这一作用是通过抑制线粒体转移而实现的。

https://orcid.org/0000-0003-3598-9747 (Yi Huang); https://orcid.org/0009-0004-1970-374X (Chenhui Zhou)

关键词: 线粒体转移, 应激性高血糖, 急性缺血性脑卒中, 脑微血管内皮细胞, 血脑屏障

Abstract: 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. 

Key words: acute ischemic stroke, blood-brain barrier, brain microvascular endothelial cells, mitochondrial transfer, stress hyperglycemia