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  • Title: Dexmedetomidine attenuates propofol-induce neuroapoptosis partly via the activation of the PI3k/Akt/GSK3β pathway in the hippocampus of neonatal rats.
    Author: Lv J, Wei Y, Chen Y, Zhang X, Gong Z, Jiang Y, Gong Q, Zhou L, Wang H, Xie Y.
    Journal: Environ Toxicol Pharmacol; 2017 Jun; 52():121-128. PubMed ID: 28411582.
    Abstract:
    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/GSK3β pathway during brain development. Seven-day-old rats were randomly exposed to 100mg/kg propofol and 100mg/kg propofol plus different doses of dexmedetomidine or 100mg/kg propofol and 75μg/kg dexmedetomidine plus PI3K inhibitor LY294002 or GSK3β inhibitor TDZD-8. TEM and TUNEL were used to detect neuronal structure changes and apoptosis. The expression of phospho-Akt, phospho-GSK3β, Akt and GSK3β 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 phospho-GSK3β, 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 phospho-Akt and phospho-GSK3β.
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