Levetiracetam Reduces Early Inflammatory Response After Intracerebral Hemorrhage By AK2-STAT3 Signaling Pathway

Background: As a antiepileptic drug,levetiracetam has been shown to alleviate the inflammatory response after various central nervous system diseases and promote the improvement of neurological function.However,its role in secondary brain injury(ICH)after cerebral hemorrhage has not been reported.Objective: The aim of this study is to investigate the effect of levetiracetam on reducing early inflammatory response after intracerebral hemorrhage and its possible mechanism.Methods: 1.In vitro experiments: Cellular models of early inflammatory responses following intracerebral hemorrhage were simulated by stimulation of microglia with LPS.Activated microglia were treated with different concentrations of LEV,and mRNA was extracted to detect the mRNA expression levels of inflammatory factors such as 1L-1? and TNF-?,and the appropriate LEV drug concentration was determined.The expression levels of NF-?B and STAT3 in microglia after LEV treatment were detected.2.Animal experiments: SD male rats were randomly divided into sham operation group,cerebral hemorrhage group,LEV solvent group and LEV group.A series of neurobehavioral tests were performed 24 hours after surgery or drug treatment,and then the rats were sacrificed to extract brain tissue.Some of them were used to measure the water content of brain tissue by dry and wet weight method,and some were used for frozen sectioning for FJC staining and detected neuronal damage,the other part was placed in a refrigerator at-20 ° C for 24 hours,and the protein was extracted to measure the protein expression levels of NF-?B,JAK2,and STAT3.All data were statistically analyzed using statistical software and charted Results: The mRNA expression levels of 1L-1? and TNF-?decreased when microglia activated by different concentrations of LEV were compared with those of LPS-stimulated microglia.Among them,good results can be obtained when the concentration of LEV is 50?g/ml.After LEV treatment of LPS-activated microglia,the relative protein expression levels of NF-?B and STAT3 were significantly decreased.FJC staining results showed that the number of degenerative neurons in the LEV group was lower than that in the cerebral hemorrhage group.The male SD rats in the LEV group had lower behavioral scores than the SD rats in the intracerebral hemorrhage group,and their neurological function was improved compared with the intracerebral hemorrhage group.The water content of brain tissue measured by the wet and dry weight method showed that the brain tissue water content of the LEV group was lower than that of the intracerebral hemorrhage group.The results of Western-blot showed that the protein expression levels of NF-?B,JAK2 and STAT3 in brain tissue of LEV group were lower than those in intracerebral hemorrhage group.Conclusion: Our study suggests that LEV can alleviate early inflammatory responses following cerebral hemorrhage by inhibiting the JAK2-STAT3 signaling pathway.LEV can also reduce the damage of neurons around the hematoma and the degree of edema of brain tissue after cerebral hemorrhage,and promote the recovery of nerve function after hemorrhage.