In summary, this study demonstrates the neuroprotective effects of dexmedetomidine combined with Netrin on cerebral ischemia-reperfusion injury and hippocampal hypoxia injury in terms of ERS, apoptosis, electrophysiology, etc. The synergistic effect of combination therapy is related to the activation of ERK5/MEF2A signaling pathway. Here, MAPK7 is linked to Cerebral ischemia.