Department of Neurology, The Affiliated Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, Liaoning, 110004, China.
J Mol Neurosci. 2014 May;53(1):50-8. doi: 10.1007/s12031-013-0196-0. Epub 2013 Dec 12.
Recently, cerebral ischemic postconditioning (Postcond) has been shown to reduce infarction volume in cerebral ischemia/reperfusion (I/R) injury. However, it is unclear if ischemic Postcond offers more extensive neuroprotection than current therapies. The aim of this study was to investigate the neuroprotective effects of ischemic Postcond on the neurovascular unit (NVU). A middle cerebral artery occlusion rat model was used; cerebral infarct volumes, neurologic scores, and transmission electron microscopy were evaluated 24 h after reperfusion. We used Evans blue extravasation, immunohistochemistry, and Western blot analyses to evaluate the integrity of the blood brain barrier (BBB) and the distribution and expression of the tight junction (TJ)-associated proteins of claudin-5 and occludin in brain microvessel endothelium. The Postcond group showed significantly reduced infarct volumes and decreased neurologic impairment scores compared to the I/R group. Also, injuries to the cerebral microvascular endothelial cells, astrocytes, and neurons were minimized in the Postcond group. The permeability of the BBB increased in both the I/R and Postcond groups, but the Postcond group showed a significant decrease in permeability than the I/R group. Expression of both claudin-5 and occludin were higher in the Postcond groups compared to the I/R group, but expression of both proteins decreased in the I/R and Postcond groups compared to the sham group. The results of our study suggest that ischemic Postcond is an effective way to reduce injury to neurons, astrocytes, and endothelial cells, to increase protein expressions of TJ-associated proteins, and to improve BBB intergrity affected by focal I/R. Ischemic Postcond could protect the NVU from I/R injury.
最近，脑缺血后处理（Postcond）已被证明可减少脑缺血/再灌注（I/R）损伤中的梗死体积。然而，缺血后处理是否比当前的治疗方法提供更广泛的神经保护作用尚不清楚。本研究旨在探讨缺血后处理对神经血管单元（NVU）的神经保护作用。使用大脑中动脉闭塞大鼠模型；再灌注后 24 小时评估脑梗死体积、神经评分和透射电镜。我们使用 Evans 蓝外渗、免疫组织化学和 Western blot 分析来评估血脑屏障（BBB）的完整性以及紧密连接（TJ）相关蛋白 Claudin-5 和 Occludin 在脑微血管内皮细胞中的分布和表达。与 I/R 组相比，Postcond 组的梗死体积明显减小，神经功能缺损评分降低。此外，Postcond 组大脑微血管内皮细胞、星形胶质细胞和神经元的损伤最小。BBB 的通透性在 I/R 和 Postcond 组中均增加，但 Postcond 组的通透性比 I/R 组显著降低。与 I/R 组相比，Postcond 组 Claudin-5 和 Occludin 的表达均升高，但与假手术组相比，I/R 和 Postcond 组的这两种蛋白表达均降低。我们的研究结果表明，缺血后处理是减少神经元、星形胶质细胞和内皮细胞损伤、增加 TJ 相关蛋白表达以及改善局灶性 I/R 引起的 BBB 完整性的有效方法。缺血后处理可保护 NVU 免受 I/R 损伤。
