Wang Qin, Yang Lin, Wang Yaping
Department of Otorhinolarynology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, China.
Department of Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, China.
Int J Dev Neurosci. 2015 Jun;43:50-7. doi: 10.1016/j.ijdevneu.2015.04.009. Epub 2015 Apr 22.
Stroke has become the leading cause of mortality worldwide. Hypoxic or ischemic insults are crucial factors mediating the neural damage in the brain tissue of stroke patients. Neural stem cells (NSCs) have been recognized as a promising tool for the treatment of ischemic stroke and other neurodegenerative diseases due to their inducible pluripotency. In this study, we aim to mimick the cerebral hypoxic-ischemic injury in vitro using oxygen-glucose deprivation (OGD) strategy, and evaluate the effects of OGD on the NSC's neural differentiation, as well as the differentiated neurite outgrowth. Our data showed that NSCs under the short-term 2h OGD treatment are able to maintain cell viability and the capability to form neurospheres. Importantly, this moderate OGD treatment promotes NSC differentiation to neurons and enhances the performance of the mature neuronal networks, accompanying increased neurite outgrowth of differentiated neurons. However, long-term 6h and 8h OGD exposures in NSCs lead to decreased cell survival, reduced differentiation and diminished NSC-derived neurite outgrowth. The expressions of neuron-specific microtubule-associated protein 2 (MAP-2) and growth associated protein 43 (GAP-43) are increased by short-term OGD treatments but suppressed by long-term OGD. Overall, our results demonstrate that short-term OGD exposure in vitro induces differentiation of NSCs while maintaining their proliferation and survival, providing valuable insights of adopting NSC-based therapy for ischemic stroke and other neurodegenerative disorders.
中风已成为全球范围内的主要死因。缺氧或缺血性损伤是介导中风患者脑组织神经损伤的关键因素。神经干细胞（NSCs）因其可诱导的多能性，已被公认为是治疗缺血性中风和其他神经退行性疾病的一种有前景的工具。在本研究中，我们旨在利用氧糖剥夺（OGD）策略在体外模拟脑缺氧缺血损伤，并评估OGD对神经干细胞神经分化以及分化后神经突生长的影响。我们的数据表明，短期2小时OGD处理下的神经干细胞能够维持细胞活力以及形成神经球的能力。重要的是，这种适度的OGD处理促进神经干细胞向神经元分化，并增强成熟神经元网络的性能，同时分化神经元的神经突生长增加。然而，神经干细胞长期暴露于6小时和8小时的OGD会导致细胞存活率降低、分化减少以及神经干细胞衍生的神经突生长减弱。短期OGD处理会增加神经元特异性微管相关蛋白2（MAP-2）和生长相关蛋白43（GAP-43）的表达，但长期OGD会抑制它们的表达。总体而言，我们的结果表明，体外短期OGD暴露可诱导神经干细胞分化，同时维持其增殖和存活，为采用基于神经干细胞的疗法治疗缺血性中风和其他神经退行性疾病提供了有价值的见解。
