cGAMP reduces neuronal damage in the mouse cerebral ischemic recovery phase by activating the PI3K-AKT pathway
Objective To determine the effect of cGAMP on the cerebral ischemia recovery phase in mice and its preliminary mechanism.Methods The middle cerebral artery occlusion(MCAO)model was established in mice with the suture method.The effect of cGAMP on the cerebral ischemia recovery phase of MCAO mice was evaluated with behavioral scoring and histopathological staining.Laser speckle instrument was used to observe the effect of cGAMP on the cerebral blood flow in MCAO model during the ischemic phase.The effect of cGAMP on the cortical neurons in MCAO mice was observed with hematoxylin-eosin(HE)and NISSL staining.The expressions of tumor necrosis factor α(TNF-α)and arginase-1(Arg-1)in the cerebral cortex of mice were detected with real-time fluorescent quantitative polymerase chain reaction(PCR),and the expressions of PI3K,p-PI3K,AKT,and p-AKT were detected with Western blot.Results Behavioral observations showed that as compared with the model group,cGAMP-treated MCAO mice during the ischemic phase displayed reduced behavioral scores and significant recovery in elevated body swing test,balance beam test,and forelimb grip traction test,indicating improved motor function.HE and NISSL staining showed that cGAMP alleviated neuronal damage in mice during the cerebral ischemia recovery phase.PCR demonstrated that cGAMP treatment reduced the expression of TNF-α in the brain tissue of mice during the cerebral ischemia recovery phase while increased the expression of Arg-1.Western blot showed that cGAMP treatment greatly promoted the phosphorylation of PI3K and AKT(P＜0.05).Conclusion cGAMP significantly improves the motor function in mice during the cerebral ischemia recovery phase,and its therapeutic effect may be attributed to the activation of the PI3K-AKT pathway to alleviate neuronal damage during the cerebral ischemia recovery phase.
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