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.