Inhibition of Pontine CaMKII Alleviates Sevoflurane-Induced Long-Term Memory Impairment in Rats
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Abstract
General anesthesia-associated cognition impairment has been becoming one of the major issues derived from medical procedure, particularly when it was performed in younger patients. Our previous data noted that early exposure of sevoflurane impaired the adulthood spatial memory function in dose and time-dependent manner. Gamma aminobutyric acid (GABA) is the key inhibitory neurotransmitter in the central nervous system, and functions through mediating Wnt signaling pathway. The pontine GABA takes a special part in keeping awakening. We in this study investigated the role of pontine GABA signaling pathway activation in sevoflurane anesthesia-related long-term cognition in infantile rats via intracranial microinjection of CaMKII inhibitor KN-93 into the pons under different minimum alveolar concentrations of seveflurane. Morris Water Maze (MWM) was used to detect the spatial memory changes after speculated interventions. The results showed that pontile inhibition of GABA-Wnt-CaMKII through blocking CaMKII substantially alleviated sevoflurane-induced long-term special memory, which demonstrated dose- and time-dependent association. These preliminary observations indicated that the pontile GABA signaling plays an essential role in sevoflurane-induced adulthood cognition impairment, and further evaluation is needed on the exact interaction among sevoflurane, GABA, glutamate, receptors, corresponding signaling mediators, and cognition alteration in the pontine region.
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Sevoflurane, Cognition, Pons, GABA, Wnt, CaMKII
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