Sevoflurane postconditioning ameliorates neuronal migration disorder through Reelin/Dab1 and improves long-term cognition in neonatal rats after hypoxic-ischemic injury

Sevoflurane postconditioning (SPC) had been reported to attenuate developing brain injury after hypoxia-ischemia encephalopathy (HIE)via inhibiting neural necrosis and autophagy process. Moreover, recent report elucidated sevoflurane may involve in neural cells migration after injury. Here we hypothesize neuronal migration and long-term cognition were ruined after HIE and SPC alleviated these injuries .Classical Rice–Vannucci model of Hypoxia-ischemia was conducted on P7 pups , which was followed by SPC at the 1 minimum alveolar concentration (MAC 2.4%) for 30 min. Piceatannol which can cleave Reelin into proteolytic fragments was used to detect whether Reelin/Dab1 is involved in neuroprotection exerted by SPC. Our findings suggest that hypoxia-ischemia disrupted cytoarchitecture of dentate gyrus (DG) by inhibiting the migration of dentate neurons of hippocampus, which may eventually lead to long-term cognition deficits. However, SPC could relieve the restricted hippocampal neurons from the subgranular zone of hippocampi combined with the repair of hippocampal-dependent memory function damaged by HIE through attenuating the overactivation of the Reelin/Dab1pathway. Taken together, these results demonstrate that SPC plays a pivotal role in ameliorating neuronal migration disorder and maintain normal cytoarchitecture and spatial learning ability of DG by regulating the Reelin/Dab1 downstream signaling pathway. This indicates the potential therapeutic use of SPC in treating HIE perinatally.