Hou Ying, Hu Zhiping, Gong Xiyu, Yang Binbin
Department of Neurology, 2nd Xiangya Hospital, Central South University Changsha, Hunan Province, China.
Aging (Albany NY). 2020 Sep 4;12(17):17568-17581. doi: 10.18632/aging.103773.
Blood brain barrier (BBB) disruption is a crucial factor contributing to secondary brain injury after intracerebral hemorrhage (ICH). Heat shock protein B8 (HSPB8) has been recently reported to confer neuroprotection against against ischaemic stroke through maintaining BBB integrity. However, the role of HSPB8 in ICH is still elusive. In this study, we found that HSPB8 was upregulated by ICH and extensively expressed in neurovascular structure including endothelial cells and astrocytes. lentivirus intracerebroventricular () injection achieved a widespread and persistent HSPB8 overexpression in brain tissues. HSPB8 overexpression significantly ameliorated neurobehavioral deficits and brain edema at 24 and 72h following ICH. Moreover, HSPB8 overexpression remarkedly inhibited BBB disruption and significantly increase the level of p-Akt, p-GSKβ and intranuclear β-catenin 24h post-ICH. This effect was obviously reversed by Akt specific inhibitor, MK2206. Based on these findings, HSPB8 exerted its protective effect on BBB, at least partly, via Akt/ p-GSKβ/β-catenin pathways.
血脑屏障（BBB）破坏是脑出血（ICH）后继发性脑损伤的一个关键因素。最近有报道称，热休克蛋白B8（HSPB8）通过维持血脑屏障的完整性对缺血性中风具有神经保护作用。然而，HSPB8在脑出血中的作用仍不清楚。在本研究中，我们发现HSPB8在脑出血后上调，并在包括内皮细胞和星形胶质细胞在内的神经血管结构中广泛表达。通过脑室内注射慢病毒实现了脑组织中HSPB8的广泛且持续的过表达。HSPB8过表达在脑出血后24小时和72小时显著改善了神经行为缺陷和脑水肿。此外，HSPB8过表达在脑出血后24小时显著抑制了血脑屏障的破坏，并显著提高了p-Akt、p-GSKβ和核内β-连环蛋白的水平。Akt特异性抑制剂MK2206明显逆转了这种作用。基于这些发现，HSPB8至少部分地通过Akt/p-GSKβ/β-连环蛋白途径对血脑屏障发挥保护作用。
