ABSTRACT
Clinical studies have found that neonatal sevoflurane exposure can increase the risk of cognitive dysfunction. However, recent studies have found that it can exhibit neuroprotective effects in some situations. In this study, we aimed to explore the effects of sevoflurane neonatal exposure in rats. A total of 144 rat pups (72 males and 72 females) were assigned to six groups and separately according to sevoflurane exposure of different times on the seventh day after birth. Blood gas analysis and western blot detection in the hippocampus were conducted after exposure. The Morris water maze test was conducted on the 32nd to 38th days after birth. The expression of PSD95 and synaptophysin in the hippocampus was detected after the Morris water maze test. We found that neonatal exposure to sevoflurane promoted apoptosis in the hippocampus, and Bax and caspase-3 were increased in a dose-dependent manner. The 2-h exposure had the greatest effects on cognitive dysfunction. However, with the extension of exposure time to 6 h, the effects on cognitive function were partly compensated. In addition, sevoflurane exposure decreased synaptogenesis in the hippocampus. However, as the exposure time was extended, the suppression of synaptogenesis was attenuated. In conclusion, neonatal sevoflurane exposure exhibited duration-dependent effects on cognitive function via Bax-caspase-3-dependent apoptosis and bidirectional effects on synaptogenesis in rats.
Subject(s)
Animals, Newborn , Cognition , Hippocampus , Sevoflurane , Sevoflurane/pharmacology , Animals , Female , Male , Hippocampus/drug effects , Hippocampus/metabolism , Rats , Cognition/drug effects , Time Factors , Maze Learning/drug effects , Anesthetics, Inhalation/pharmacology , Anesthetics, Inhalation/adverse effects , Apoptosis/drug effects , Sex Factors , Rats, Sprague-Dawley , Methyl Ethers/pharmacology , Blotting, Western , Blood Gas Analysis , Cognitive Dysfunction/chemically inducedABSTRACT
Objective The sedative dexmedetomidine plays a role in multi-organ protection by inhibiting toll-like receptor (TLR) 4 expression in ischemia/reperfusion injury. The present study investigated whether the neuroprotective effects of dexmedetomidine could be blocked by the TLR4 agonist lipopolysaccharide. Methods We established a cerebral ischemia/reperfusion model in neonatal Sprague-Dawley rats through bilateral carotid artery occlusion for 20 minutes followed by a 2-hour reperfusion. Rats were assigned to four groups: Sham operation, ischemia/reperfusion, ischemia/reperfusion preceded by dexmedetomidine treatment (10 µg/kg), and ischemia/reperfusion preceded by dexmedetomidine (10 µg/kg) and lipopolysaccharide (500 µg/kg) treatments. Cerebral tissue injury was assessed by hematoxylin and eosin staining, and cerebral TLR4 expression was evaluated by real-time PCR and western blot. Results Pretreatment with dexmedetomidine reduced ischemia-induced morphological changes in the hippocampal CA3 region and downregulated TLR4 expression, but these neuroprotective effects were partially blocked by co-treatment with the TLR4 agonist lipopolysaccharide. Conclusion Our results indicate that inhibition of cerebral TLR4 expression is related to the neuroprotective effects of dexmedetomidine in this neonatal rat cerebral ischemia/reperfusion model.
