Dexmedetomidine Post-conditioning Ameliorates Long-term Neurological Outcomes After Neonatal Hypoxic Ischemia: The Role of Autophagy

Background: Hypoxic-ischemic brain injury (HIBI) is a major cause of mortality in neonates and can cause long-term neurological sequelae. Excessive autophagy caused by HI may cause neuronal death. Dexmedetomidine was reported neuroprotective against HIBI. Therefore, in the present study, the autophagy-related mechanisms underlying the protective effects of dexmedetomidine against cerebral HI in neonatal rats were investigated.

Methods: In the present study, the expression of autophagy-related proteins microtubule-associated protein 1 light chain 3 (LC3) B-II and Beclin1, neuronal and microglia autophagy levels, the myelin basic protein (MBP) expression, long-term neuronal density ratio, and long-term behavioral prognosis in HIBI model were investigated by ligating the left common carotid artery in neonatal rats, followed by 2-h hypoxia.

Results: Dexmedetomidine inhibited the overactivated autophagy of hippocampal neurons and microglia after HI. In addition, dexmedetomidine inhibited neuronal density decrease and axon demyelination after HI-induced overactivated autophagy. Lastly, dexmedetomidine improved the long-term neurological prognosis and was reversed by the autophagy agonist rapamycin.

Conclusion: The protective effects of dexmedetomidine on HI neonatal rats were evidenced by inhibition of excessive autophagy of neurons and microglia, thereby reducing the decline of long-term neuronal density and axon demyelination as well as improving long-term learning cognitive function.