Department of Pharmacology, School of Medical Sciences, UNSW, Sydney, New South Wales 2052, Australia.
Neurodegeneration and Repair Unit, School of Medical Sciences, UNSW, Sydney, New South Wales 2052, Australia.
Exp Neurol. 2018 Aug;306:177-189. doi: 10.1016/j.expneurol.2018.05.018. Epub 2018 May 17.
Stroke is a leading cause of death and a major contributor to neurological disability in adults. Tissue plasminogen activator is the only approved treatment. However, due to its narrow therapeutic window, <5% of patients receive treatment. Recently, hypoxic postconditioning (HPC) was shown to reduce stroke induced-injury in mice, but the mechanisms and functional outcomes are still unknown. In the current study, male Sprague Dawley rats were subjected to endothelin-1 induced stroke. HPC (8% O, 1 h/d for 5d) or normoxia treatments were started 24 h after stroke. Behavioural tests were performed at various time-points (pre- and post-surgery, 1 and 6 days post stroke) and brains were collected 6 days after stroke for histological and immunoblotting analysis. HPC improved deficits in neurological score, motor and sensory function after stroke. Furthermore, HPC reduced infarct volume and neuronal loss in the cortex, while it increased the number of astrocytes and of Fluoro-Jade-positive cells in the injured hemisphere. We observed a mild increase in HIF-1 and its target gene, glucose transporter-1. Our data suggest that HPC-induced neuroprotection was mediated by enhanced astrocyte function, which may have contributed to functional recovery after stroke.
中风是成年人死亡的主要原因之一，也是导致神经功能障碍的主要原因。组织型纤溶酶原激活物是唯一被批准的治疗方法。然而，由于其治疗窗口狭窄，只有不到 5%的患者接受治疗。最近，缺氧后处理（HPC）已被证明可减少小鼠中风引起的损伤，但机制和功能结果仍不清楚。在本研究中，雄性 Sprague Dawley 大鼠接受内皮素-1 诱导的中风。中风后 24 小时开始进行 HPC（8% O2，每天 1 小时，共 5 天）或常氧处理。在不同时间点（术前和术后、中风后 1 天和 6 天）进行行为测试，并在中风后 6 天收集大脑进行组织学和免疫印迹分析。HPC 改善了中风后的神经评分、运动和感觉功能障碍。此外，HPC 减少了皮质中的梗死体积和神经元丢失，同时增加了损伤半球中星形胶质细胞和 Fluoro-Jade 阳性细胞的数量。我们观察到 HIF-1 及其靶基因葡萄糖转运蛋白-1 的轻度增加。我们的数据表明，HPC 诱导的神经保护是通过增强星形胶质细胞功能介导的，这可能有助于中风后的功能恢复。
