Age-related Differences In Innate Immune Responses To Ischemia Stroke

Objective:The inflammatory response is the basic pathophysiological process after cerebral ischemic injury.The most important response is the rapid activation of innate immune cells in the brain,mainly microglia(MG).After activation,MG is activated Different is divided into M1 classic activation(proinflammatory)and M2 selective activation(anti-inflammatory),so that microglia is the latest treatment target to limit the damage after cerebral ischemia.Although the occurrence of ischemic stroke and aging,inflammation increases are inextricably linked,but after a short period of time after cerebral ischemia and age-related pathogenesis is still unknown,and the elderly brain physiological and biochemical status and young The brain is very different,the reaction to inflammation is also very likely different.In this study,we examined the expression of M1 / M2 markers and the expression of peripheral inflammatory mediators in different age cerebral ischemia and reperfusion,and discussed the regularity and difference of microglia activation in young and aged brains after ischemic stroke.Methods: In this study,the middle cerebral artery occlusion model(MCAO)was used to simulate cerebral ischemic injury.The healthy male C57 BL / 6 wild type(WT)mice were randomly selected from 3 months old and 18 months old,respectively.Model group and sham operation group.The rats in the model group were treated with modified suture method to establish the middle cerebral artery occlusion and reperfusion focal cerebral ischemia model.After 90 minutes of ischemia,the rats in the model group were treated with 1 day,3 days and 7 days,Each time point 18.The infarct volume was measured by TTC staining,and the levels of Arg1 were detected by immunoblotting(WB)and INOS and M2 markers.The immunofluorescence staining was used to detect the infarct volume,Immunohistochemistry(ELISA)was used to detect the expression of proinflammatory cytokines TNF-?,INOS,IL-6,IL-6 and IL-4 and IL-4,IL-10 and TGF-?1 were detected by immunohistochemistry.Finally,the difference between the aged brain and the young brain was analyzed by one-way ANOVA and independent sample T test.Results:1 day,3 days and 7 days after infusion of cerebral ischemia 1 day,3 days,7 days after the infarct volume: old mice 1 day,3 days,7 days were smaller than the young mice1 day,3 days,7 days infarct volume,and the time There was significant difference between the two groups(P <0.01).2 neurological deficit score: compared with the infarct volume comparison results,older mice in 1 day,3 days,7 days neurological deficit scores were higher than the young mice1 day,3 days,7 days neurological deficit score,and each There was significant difference between the two groups(P <0.01).All the neurological deficits in the elderly group and the young group were the same as above.The expression of Arg1 in the sham operation group and the three time points in the old group began to decline after the peak of the third day,and the young group rose steadily on the first day until the peak of the 7th day.(P <0.05).The expression level of young group was significantly higher than that of the old group(P <0.05).The young group showed a significant increase in sham,1 day,3 days and 7 days,and the difference was statistically significant(P values ??were less than 0.05 for the young group sham.VS1 day.VS.3.day.VS.7day).The anti-inflammatory factors gradually increased after cerebral ischemia-reperfusion.In the elderly group,the anti-inflammatory factors were gradually increased after cerebral ischemia-reperfusion,and the level of M1 in the elderly group was significantly higher than that in the young group.4 Immunofluorescence: There was no significant difference in the expression of microglia in the elderly group and the young group(sham.VS.young sham P> 0.05).In the elderly group,the expression of CD206 gradually increased to the seventh day at the time of ischemia-reperfusion,and MHC? reached the peak on the first day,and then decreased gradually.Three time data were statistically significant(senile group 1day.VS.3 days.VS.7 days P <0.05).The expression of CD206 was significantly higher in the young group than in the elderly group,and the expression of MHC? was significantly lower than that of the elderly group(senile / young group 1 day.VS.Elderly/ young group 3 days VS.Elderly / young group 7 Day P <0.05).(IL-4,IL-10,TGF-?1)levels in peripheral blood group were significantly different from those in the control group(P <0.05),but there was no significant difference between the two groups The release of the body in the elderly group was significantly higher than that in the young group,and the antiinflammatory factor was significantly lower than that in the young group.Inflammatory factors are more delayed than brain tissue neuritis.Conclusion: Our experimental results show that: after cerebral ischemia,the brain of the elderly and the young brain have different inflammatory reaction process.The proinflammatory effect of M1 mainly occurs in the first 3 days after cerebral ischemia and reperfusion,and the anti-The effect is played late in 3 to 7 days.The size of the young cerebral infarction has a greater infarct volume than the older brain,but the lesser neurological deficits,lower mortality and better prognosis,the level of peripheral brain proinflammatory cytokine release in the elderly is significantly higher than that of the young brain and the antiinflammatory factor Release level is low.Nervous system inflammation can cause systemic systemic inflammatory response.