Carbenoxolone does not Improve Sevoflurane-induced Neurotoxicity in the Developing Rat Hippocampus

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Abstract Background: Connexin 43 is the most abundant connexin protein expressed in astrocytes. Our previous research found that sevoflurane-induced neurotoxicity was related to Cx43 via JNK/MAPK/Ap-1 signaling pathway. Cx43 functions through hemichannels (HCs) and gap junctions (GJs) and both of them could affect the homeostasis of central nervous system. Carbenoxolone (Cbx) is generally considered as a Cx43 hemichannel and gap junction inhibitor in traditional applications. Therefore, we hypothesized that preadministration of Cbx may attenuate sevoflurane-induced cognitive dysfunction.Methods: Seven-day-old SD rats (P7) were exposed to 3% sevoflurane for 4 hours with or without Cbx pretreatment at a dose of 50 mg/kg. Levels of Bcl-2, Bax, Cx43 and caspase-3 positive cells in P8 rat’s hippocampus were examined using Western blotting and immunohistochemistry. Morris water maze was performed from P28 to P33 to test the cognitive function.Results: Cx43 levels and caspase-3 positive cells in P7 rat hippocampus were increased 1 day after exposure to 3% sevoflurane for 4 h compared with control rats. Sevoflurane anesthesia decreased the expression of Bcl-2 and increased the expression of Bax in P8 rat’s hippocampus (P<0.05, n=5). Exposure to sevoflurane led to significant cognitive impairment from P28 to P33.All these defects could not be alleviated by pretreatment with Cbx.Conclusions: These data suggested that Cbx could not improve sevoflurane-induced neurotoxicity by inhibiting Cx43 HCs in the developing brain.

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