Experimental Study Of Lithium Chloride In The Treatment Of Experimental Autoimmune Encephalomyelitis

Background: Multiple sclerosis(MS)is typical autoimmune disease occurring in central nerve system(CNS).Characterized by replase of inflammation and other symptoms,the disorder mainly impaired population aged from 15 to 50.Traditional treating modalities against MS are comprehensive therapies.However,even being handled timely,MS can only be alleviated instead of being healed by comprehensive therapies.Therefore,development of therapeutic strategies for treatment of MS has become a critical issue in clinic.Lithium has been employed as the first-line therapy for amelioration of bipolar disorder(BD).Additionally,lithium is also capable of protecting CNS and modulating the activity of several immune cells.Based on previous studies,administration of experimental autoimmune encephalomyelitis animals(EAE)with lithium is an effective therapy for treatment of the disorder,which might depend on the function of IFN-γ.Taken together,it is reasonable to determine the effect of lithium on MS as well as exploring the mechanism involved in the treatment,data of which will promote the prognosis of MS patients as well as identification of therapeutic target for therapy development.Thus,in the current study,the major purpose was to assess the effect of lithium on MS in a condition without IFN-γfunctioning and to detect the role of β-catenin in the treating effect of lithium on MS.Objective: To explore the interaction between lithium and IFN-γ as well as β-catenin in treating MS.Methods:1.Identification of IFN-γR deficiency mice with PCR method.2.Induction of EAE in IFN-γR deficiency mice with MOG35-55 and pertussis toxin.3.Recording and analysis of proportion of atypical symptoms of cerebral inflammation.4.Recording and analysis of score of typical symptoms of spinal cord inflammation.5.Determination of inflammation in cerebral and spinal cord tissues using H&E staining.6.Administration of mice cerebral endothelial cell line b END.3 with lithium chloride and IFN-γ.7.Determination of β-catenin in b END.3 cells with western blotting.Result:1.Mice employed in the current study was IFN-γ-/-type based on PCR validation.2.EAE was successfully induced in IFN-γR deficiency mice.3.Administration of lithium decreased proportion of atypical symptoms of cerebral inflammation and average score of typical symptoms of spinal cord inflammation.4.Administration of lithium alleviated inflammation in cerebral and spinal cord tissues.5.The inflammation inhibiting effect of lithium was independent of IFN-γ function.6.The protective effect of lithium on CNS in IFN-γR deficiency mice was short-term.7.Administration of lithium and IFN-γ up-regulated expression of β-catenin in b END.3cells.Conclusion: Administration of lithium could induced the production of β-catenin,which contributed to control of onset of EAE.The effect of lithium on inflammation in CNS could be exerted in a IFN-γ independent manner,but instead of functioning chronically,the effect of lithium on MS in IFN-γ deficiency condition was short-term.