Neuroprotection of the Developing Brain by Dexmedetomidine Is Mediated by Attenuating Single Propofol-induced Hippocampal Apoptosis and Synaptic Plasticity Deficits.

Dexmedetomidine (DEX) has neuroprotective effects and its efficacy was determined in propofol-treated pups. Postnatal day (P) 7 rats were exposed to propofol and DEX to investigate the induced apoptosis-related gene expression. Furthermore, synaptic structural changes at the cellular level were observed by electron microscopy. Induction of hippocampal long-term potentiation (LTP) of P30 rats and long-lasting performance of spatial discrimination at P30 and P60 were evaluated. After a single propofol exposure to P7 rats, DEX pretreatment effectively rescued the profound apoptosis seen in hippocampal neurocytes, and strongly reversed the aberrant expression levels of Bcl2-like 1 (BCL2L1), matrix metallopeptidase 9 (MMP-9) and cleaved caspase 3 (CC3), and sharply enhanced synaptic plasticity. However, there were no significant differences in escape latency or crossing times in a probe test. This was accompanied by no obvious reduction in search strategies among the rat groups. No impairment of long-term learning and memory in P30 or P60 rats was detected when using a single dose propofol treatment during the most vulnerable period of brain development. DEX was shown to ameliorate the rodent developmental neurotoxicity caused by a single neonatal propofol challenge, by altering MMP-9, BCL2L1 and CC3 apoptotic signaling.