Department of Neurology, Key Laboratory of Neurology of Hebei Province, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, People's Republic of China.
Department of Emergency, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, People's Republic of China.
Brain Res. 2019 Jul 1;1714:88-98. doi: 10.1016/j.brainres.2019.02.011. Epub 2019 Feb 12.
Cognitive impairment is one of the most common and disabling co-morbidities of epilepsy. It is therefore imperative to find novel treatment approaches to rescue cognitive function among epilepsy patients. Adult neurogenesis is strongly implicated in cognitive function, and mild hypoxia is known to promote the proliferation and differentiation of both embryonic and adult neural stem cells (NSCs). In the present study, we investigated the effect of mild hypoxia on cognitive function and hippocampal neurogenesis of rats with pilocarpine-induced chronic epilepsy. Chronic epilepsy induced marked spatial learning and memory deficits in the Morris water maze that were rescued by consecutively 28 days mild hypoxia exposure (6 h/d at 3000 m altitude equivalent) during the chronic phase. Moreover, mild hypoxia reversed the suppression of hippocampal neurogenesis and the downregulation of NT-3 and BDNF expression in hippocampus and cortex of epileptic rats. Mild hypoxia in vitro also promoted hippocampus-derived NSC proliferation and neuronal differentiation. In addition, mild hypoxia enhanced Notch1 and Hes1 expression, suggesting that Notch1 signaling may be involved in neuroprotection of hypoxia. Our data may help to pave the way for identifying new therapeutic targets for rescuing cognition conflicts in epileptic patients by using hypoxia to promote hippocampus neurogenesis.
认知障碍是癫痫最常见和致残的共病之一。因此，必须寻找新的治疗方法来挽救癫痫患者的认知功能。成人神经发生强烈参与认知功能，并且已知轻度缺氧可促进胚胎和成年神经干细胞（NSC）的增殖和分化。在本研究中，我们研究了轻度缺氧对匹鲁卡品诱导的慢性癫痫大鼠认知功能和海马神经发生的影响。慢性癫痫在 Morris 水迷宫中引起明显的空间学习和记忆缺陷，而在慢性期连续 28 天的轻度缺氧暴露（相当于 3000 米海拔高度的 6 小时/天）可挽救这些缺陷。此外，轻度缺氧逆转了癫痫大鼠海马神经发生的抑制和海马和皮质中 NT-3 和 BDNF 表达的下调。体外轻度缺氧还促进了海马源性 NSC 的增殖和神经元分化。此外，轻度缺氧增强了 Notch1 和 Hes1 的表达，表明 Notch1 信号可能参与了缺氧的神经保护作用。我们的数据可能有助于为通过使用缺氧促进海马神经发生来确定挽救癫痫患者认知冲突的新治疗靶点铺平道路。
