Teo Jonathan D, Morris Margaret J, Jones Nicole M
Department of Pharmacology, School of Medical Sciences, University of New South Wales, New South Wales, Australia.
Pediatr Res. 2015 Jun;77(6):757-64. doi: 10.1038/pr.2015.47. Epub 2015 Mar 9.
Postconditioning (PostC) with mild hypoxia shortly after a neonatal hypoxic-ischemic (HI) brain injury can reduce brain damage, however, the mechanisms underlying this protection are not known. We hypothesize that hypoxic PostC reduces brain markers of glial activity, inflammation, and apoptosis following HI injury.
Sprague Dawley rat pups were exposed to right common carotid artery occlusion and hypoxia (7% oxygen, 3 h) on postnatal day 7 and 24 h later, pups were exposed to hypoxic PostC (8% O2 for 1 h/day for 5 d) or kept at ambient conditions for the same duration. HI+N pups demonstrated ~10% loss in ipsilateral brain tissue which was rescued with HI+PostC. To investigate the cellular responses, markers of astrocytes, microglia, inflammation, and caspase 3 activity were examined using immunohistochemistry and enzyme-linked immunosorbent assay.
PostC reduced the area of astrocyte staining compared to HI+N. There was also a shift in microglial morphology toward a primed state in both PostC groups. Protein levels of interleukin-1β and caspase 3 were elevated in HI+N brains and reduced by PostC.
This is the first demonstration that PostC can reduce glial activity, inflammatory mediators, and cell death after a neonatal HI brain injury.
新生儿缺氧缺血性（HI）脑损伤后不久进行轻度缺氧后处理（PostC）可减少脑损伤，然而，这种保护作用的潜在机制尚不清楚。我们假设缺氧后处理可降低HI损伤后神经胶质细胞活性、炎症和细胞凋亡的脑标志物水平。
将出生后第7天的斯普拉格-道利大鼠幼崽暴露于右侧颈总动脉闭塞和缺氧（7%氧气，3小时）环境中，24小时后，将幼崽暴露于缺氧后处理（8%氧气，每天1小时，共5天）或在相同时间内保持在环境条件下。HI+N组幼崽同侧脑组织损失约10%，而HI+PostC组则得到挽救。为了研究细胞反应，使用免疫组织化学和酶联免疫吸附测定法检测星形胶质细胞、小胶质细胞、炎症和半胱天冬酶3活性的标志物。
与HI+N组相比，后处理减少了星形胶质细胞染色面积。两个后处理组的小胶质细胞形态也都向预激活状态转变。HI+N组脑内白细胞介素-1β和半胱天冬酶3的蛋白水平升高，而后处理使其降低。
这是首次证明后处理可降低新生儿HI脑损伤后的神经胶质细胞活性、炎症介质和细胞死亡。
