The effect of hypothermia therapy on cortical laminar disruption following ischemic injury in neonatal mice

P3小鼠右颈总动脉结扎后缺氧（6% O2, 37°C） 30min，诱导脑缺血。小鼠缺氧缺血后立即低温或常温处理24小时，免疫组化（Cux1/Ctip2）检测皮层层状结构；计算神经元数量；测定髓鞘碱性蛋白（MBP）的表达。在行为测试中，低温治疗与神经学结果的改善有关。在正常体温组，组织学分析表明，与对侧皮质相比，神经元数量减少，深部皮质层厚度减少，缺血皮质中MBP表达明显减少。在低温组中，与对侧皮质相比，深部皮质层厚度和缺血皮质的MBP表达没有减少。本研究结果可为早产儿缺氧缺血脑瘫患者低温治疗试验提供依据。

Cerebral ischemia was induced in P3 mice with a right common carotid artery ligation followed by hypoxia (6% O2, 37 °C) for 30 min. Immediately after hypoxic ischemia, mice were exposed to hypothermia or normothermia for 24 h. The laminar structure of the cortex was examined with immunohistochemistry (Cux1/Ctip2); the number of neurons was counted; and the expression of myelin basic protein (MBP) was determined. The hypothermia treatment was associated with improved neurological outcomes in the behavioral test. In the normothermia group, histological analyses indicated reduced numbers of neurons, reduced cortical laminar thickness in the deep, ischemic cortical layers, and significant reduction in MBP expression in the ischemic cortex compared to the contralateral cortex. In the hypothermia group, no reductions were noted in deep cortical layer thickness and in MBP expression in the ischemic cortex compared to the contralateral cortex. Our findings may provide a basis for testing hypothermal therapies in patients with cerebral palsy induced by hypoxic ischemia in the preterm period.