Propofol, a commonly used intravenous anesthetic, has been associated with neurodegeneration in the developing brain upon repeated exposure. Dexmedetomidine is an α2 adrenoceptor agonist that was previously reported to possess neuroprotective properties. Here, we confirmed the impacts of dexmedetomidine on propofol-induced neuroapoptosis and subsequent spatial learning and memory deficits in neonatal rats. We found that dexmedetomidine effectively mitigated propofol-induced spatial learning and memory impairments and improved aversive memory in developing rats. Dexmedetomidine reduced propofol-induced cell apoptosis in the hippocampus and modulated the mRNA expression of Bcl-2 and Bax. Additionally, dexmedetomidine attenuated the propofol-induced increase of inflammatory factors IL-6 and TNF-α. The reduced phosphorylation levels of Akt and CREB levels by propofol were re-activated by dexmedetomidine. In conclusion, our findings demonstrated that dexmedetomidine effectively mitigated propofol-induced cognitive and memory impairments in developing rats by modulating apoptosis and reducing inflammation via activating the Akt/CREB/BDNF signaling pathway. These findings suggest potential strategies to protect the developing brain from the adverse effects of anesthetics and improve patient care in pediatric anesthesia practice.
Weiren Xiao, Shouren Chen, Jinzhuan Chen, & Jianzhong Huang.
International Journal of Developmental Neuroscience: The Official Journal of the International Society for Developmental Neuroscience August 2023