Mechanism of mild hypothermia induced cold shock protein protecting neural stem cells

Cardiac arrest (CA) is a leading cause of death in humans. Our previous research confirmed that after CA/cardiopulmonary resuscitation, mild therapeutic hypothermia (MH) promotes neurogenesis in the brain and earlier expression of RNA-binding motif protein 3 (RBM3) in the cerebral cortex and hippocampus of rats. However, the mechanism underlying RBM3 regulating MH-induced neurogenesis remains unclear. This study simulated I/R injury after CA by oxygen-glucose deprivation/reperfusion (OGD/R) of mouse NSCs to determine whether RBM3 mediates the neuroprotective effects of MH in neural stem cells (NSCs) after ischemia-reperfusion (I/R) injury and whether this mechanism involves the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. The experimental results showed that the number of newborn NSCs increased significantly in the hypothermic group on days 3 and 5 after OGD/R injury compared with the normothermic group, and the apoptosis of NSCs decreased significantly, we also found that the proportion of NSCs differentiated into neuroglial cells decreased, while the proportion of NSCs differentiated into neurons increased. In NSCs, MH increased the expression of RBM3 after OGD/R injury and activated the PI3K/AKT signaling pathway. By inhibiting this pathway, the effects of MH on promoting NSCs' proliferation and differentiation and inhibiting their apoptosis were eliminated.