Enhanced differentiation of neural stem cells to neurons and promotion of neurite outgrowth by oxygen–glucose deprivation

Abstract

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.

Analytic Models of Oxygen and Nutrient Diffusion, Metabolism Dynamics, and Architecture Optimization in Three-Dimensional Tissue Constructs with Applications and Insights in Cerebral Organoids

“…In the second zone, marginally lower oxygen levels may promote expansion of neuroglial precursor populations, a phenomenon which has been observed in cell cultures with controlled hypoxia levels [11][12][13] . In the central region of still lower oxygen levels, stem cell pluripotency may be maintained, as has also been observed in cell cultures with controlled hypoxia levels [4][5][6]14 , although other evidence has also suggested that hypoxia can induce differentiation [9][10]18 . Finally, zone 4 represents a potential hypoxic region where cell function and viability are threatened.…”

Hypoxic preconditioning ameliorated neuronal injury after middle cerebral artery occlusion by promoting neurogenesis

“…The condition of incubator was controlled as followed: 1% O 2 , 5% CO 2 , 94% N 2 , 37°C. The cells were subjected to treatment of oxygen glucose deprivation at different periods (3, 5, 8, and 10 hr) (Wang, Yang, & Wang, 2015).…”

Melatonin antagonizes interleukin‐18‐mediated inhibition on neural stem cell proliferation and differentiation

“…NSCs are pluripotent, undifferentiated and self‐renewing neuronal precursor cells. NSC's transplantation has been promulgated as a promisingly attractive strategy for spinal cord injury and neurodegenerative disorders . NSC can replace lost oligodendrocytes and neurons, and this replacement contributes to the restoration of motor function in animal models .…”