Dexmedetomidine attenuates propofol-induce neuroapoptosis partly via the activation of the PI3k/Akt/GSK3β pathway in the hippocampus of neonatal rats

Recent studies have demonstrated that propofol causes neurodegeneration in developing brains. Evidence has shown that dexmedetomidine has neuroprotective effects. However, whether dexmedetomidine can reduce propofol-induced neuroapoptosis and by what mechanisms it acts remain unclear. We investigated whether dexmedetomidine can attenuate propofol-induced neuroapoptosis by disturbing the PI3K/Akt/GSK3 beta pathway during brain development. Seven-day-old rats were randomly exposed to 100 mg/kg propofol and 100 mg/kg propofol plus different doses of dexmedetomidine or 100 mg/kg propofol and 75 g/kg dexmedetomidine plus PI3K inhibitor LY294002 or GSK3 beta inhibitor TDZD-8. TEM and TUNEL were used to detect neuronal structure changes and apoptosis. The expression of phospho-Akt, phospho-GSK3 beta, Akt and GSK3 beta were quantified using western blots and immunofluorescence. Pretreatment with different doses of dexmedetomidine protected against propofol-induced neuroapoptosis. Furthermore, propofol decreased the levels of phospho-Akt and phosphoGSK313, whereas dexmedetomidine partially reversed this inhibition. In addition, treatment with LY294002 inhibited the neuroprotection of dexmedetomidine, whereas TDZD-8 enhanced neuroprotection. Our results indicate that dexmedetomidine prevents propofol-induced neuroapoptosis by increasing the levels of phosphoAkt and phospho-GSK3 beta.