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

P3小鼠采用右侧颈总动脉结扎+低氧(6%O2，37℃)30min造成脑缺血模型。小鼠缺氧缺血后立即给予低温或常温处理24 h，用免疫组织化学方法(CUX1/Ctip2)观察大脑皮层的板层结构，计数神经元数目，并测定髓鞘碱性蛋白(MBP)的表达。低温治疗与行为测试中神经学结果的改善有关。在常温组，组织学分析显示，与对侧皮质相比，常温组神经元数量减少，缺血皮质深层皮质层厚度减少，MBP表达显著减少。在亚低温组，与对侧皮层相比，缺血区皮质深层厚度和MBP表达均未见减少。我们的研究结果可能为检验早产期缺氧缺血所致脑性瘫痪患者的降温治疗提供依据。

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.