Enhanced differentiation of neural stem cells to neurons and promotion of neurite outgrowth by oxygen-glucose deprivation.
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.
Department of Otorhinolarynology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, China.
Qin
Q
Wang
Department of Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, China.
Lin
L
Yang
Department of Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, China. Electronic address: ypwang1234@163.com.
Yaping
Y
Wang
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D015687:Cell Hypoxia / Q000502:physiology*; D002465:Cell Movement; D002470:Cell Survival; D019922:GAP-43 Protein / Q000235:genetics / Q000378:metabolism; D005947:Glucose / Q000172:deficiency*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells; D016501:Neurites / Q000502:physiology*; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D051381:Rats; D013997:Time Factors
D019922:GAP-43 Protein; C489787:MAP2 protein, rat; D008869:Microtubule-Associated Proteins; D007770:L-Lactate Dehydrogenase; D005947:Glucose; D002118:Calcium
Differentiation; Neural stem cells; Oxygen–glucose deprivation; Proliferation