Facilitation of Neural Stem Cell Migration by Microglial Activation upon Oxygen-glucose Deprivation via SDF1α/CXCR4 Pathway

Background: Ischemic stroke is the most common cause of ischemia-related death globally. Brain injuries due to stroke and trauma are typically followed by inflammation reactions within the central nervous system (CNS). Neural stem cell (NSC)-based therapeutic strategies show great potential for treating stroke and ischemia-mediated brain injuries, and migration of NSCs is a critical step involved in NSC-based therapy. Methods: In order to examine the effects of microglial activation upon ischemia and stroke on NSC behaviors, oxygen-glucose deprivation (OGD) in vitro model was established for mimicking in vivo stroke and ischemia pathological conditions in this study. By combining of enzyme-linked immunosorbent assay, migration assay, Western blot and immunostaining, we found that OGD insult induced microglial activation by releasing cytokines and chemokines. Results: The conditioned media (CM) of OGD-treated groups impaired the proliferation and capability of neurosphere formation. Moreover, we found the stromal cell-derived factor 1α/CXC chemokine receptor 4 (CXCR4) pathway was an active player that facilitated the migration of NSCs, since a CXCR4 specific antagonist AMD3100 was able to impair NSC migration both in vitro and in vivo. Conclusion: The current study presents a potential interaction between NSC behaviors and microglial activation underlying brain injuries, such as ischemia and stroke. More importantly, we reveal the underlying mechanisms of microglia-induced NSC migration under OGD conditions and it should be beneficial to stem cell-based therapies to treat acute brain injuries.