Department of Pathology, School of Basic Medical Science, Ningxia Medical University, Ningxia Key Laboratory of Cerebrocranial Diseases, Incubation Base of National Key Laboratory, Yinchuan, Ningxia 750004, P.R. China.
Department of Pharmaceutical Sciences, Biomanufacturing Research Institute and Technological Enterprise, College of Health and Sciences, North Carolina Central University, Durham, NC 27707, USA.
Int J Mol Med. 2021 Jul;48(1). doi: 10.3892/ijmm.2021.4975. Epub 2021 Jun 3.
Hyperglycemia aggravates brain damage caused by cerebral ischemia/reperfusion (I/R) and increases the permeability of the blood‑brain barrier (BBB). However, there are relatively few studies on morphological changes of the BBB. The present study aimed to investigate the effect of hyperglycemia on BBB morphological changes following cerebral I/R injury. Streptozotocin‑induced hyperglycemic and citrate‑buffered saline‑injected normoglycemic rats were subjected to 30 min middle cerebral artery occlusion. Neurological deficits were evaluated. Brain infarct volume was assessed by 2,3,5‑triphenyltetrazolium chloride staining and BBB integrity was evaluated by Evans blue and IgG extravasation following 24 h reperfusion. Changes in tight junctions (TJ) and basement membrane (BM) proteins (claudin, occludin and zonula occludens‑1) were examined using immunohistochemistry and western blotting. Astrocytes, microglial cells and neutrophils were labeled with specific antibodies for immunohistochemistry after 1, 3 and 7 days of reperfusion. Hyperglycemia increased extravasations of Evan's blue and IgG and aggravated damage to TJ and BM proteins following I/R injury. Furthermore, hyperglycemia suppressed astrocyte activation and damaged astrocytic endfeet surrounding cerebral blood vessels following I/R. Hyperglycemia inhibited microglia activation and proliferation and increased neutrophil infiltration in the brain. It was concluded that hyperglycemia‑induced BBB leakage following I/R might be caused by damage to TJ and BM proteins and astrocytic endfeet. Furthermore, suppression of microglial cells and increased neutrophil infiltration to the brain may contribute to the detrimental effects of pre‑ischemic hyperglycemia on the outcome of cerebral ischemic stroke.
高血糖加重脑缺血/再灌注（I/R）引起的脑损伤，并增加血脑屏障（BBB）的通透性。然而，关于 BBB 形态变化的研究相对较少。本研究旨在探讨高血糖对脑 I/R 损伤后 BBB 形态变化的影响。链脲佐菌素诱导的高血糖和柠檬酸盐缓冲盐水注射的正常血糖大鼠接受 30 分钟大脑中动脉闭塞。评估神经功能缺损。通过 2,3,5-三苯基氯化四氮唑染色评估脑梗死体积，通过 24 小时再灌注后 Evans 蓝和 IgG 外渗评估 BBB 完整性。用免疫组化和 Western blot 检测紧密连接（TJ）和基底膜（BM）蛋白（claudin、occludin 和 zonula occludens-1）的变化。再灌注后 1、3 和 7 天，用特异性抗体进行免疫组化标记星形胶质细胞、小胶质细胞和中性粒细胞。高血糖增加了 Evans 蓝和 IgG 的外渗，并加重了 I/R 损伤后 TJ 和 BM 蛋白的损伤。此外，高血糖抑制了 I/R 后星形胶质细胞的激活和损伤星形胶质细胞围绕脑血管的足突。高血糖抑制小胶质细胞的激活和增殖，并增加中性粒细胞在脑内的浸润。结论：I/R 后高血糖引起的 BBB 渗漏可能是由 TJ 和 BM 蛋白以及星形胶质细胞足突损伤引起的。此外，小胶质细胞的抑制和中性粒细胞向脑内的浸润增加可能是缺血前高血糖对脑缺血性中风结局的有害影响的原因。
