Mechanism Of Exercise Preconditioning Regulating PGC-1α/FNDC5/BDNF Singnaling Pathway On Neurological Function After Cerebral Ischemia/reperfusion

Objective:To elucidate the mechanism of exercise preconditioning regulating PGC-1α/FNDC5/BDNF signaling pathway on neuological function in cerebral ischemia/reperfusion rats,and to provide a reliable theoretical basis for exercise training prevention and treatment of stroke.Methods:The 160 SD rats were randomly divided into 4 groups,namely the sham group,the model group(Model group),the exercise preconditioning + sham group(P-Sham group)and the exercise preconditioning + model group(P-Model group),with 40 rats in each group.The rats in the P-Sham group and the P-Model group were given 4 weeks of exercise preconditioning on computer controlled-rotary wheeled treadmill for 30 minutes per day.24 h after the last exercise preconditioning,the rats in each group underwent MCAO model preparation.After 7d of reperfusion,TTC staining was used to detect cerebral infarct volume.After reperfusion for 1d,3d and 7d,modified neurological severity score was used to evaluate the degree of neurological deficits of each group;HE staining observed the pathological morphological changes of the ischemic brain tissue in rats;ELISA determined the content of ERRα and Irisin in the blood;Immunofluorescence staining was used to detect the positive expression of BDNF/Neu N in ischemic brain tissue;The expression of PGC-1α,FNDC5,and BDNF proteins in ischemicl brain tissue was tested by Western blot.Results:1.m NSS results: After cerebral ischemia reperfusion for 1d,3d,and 7d,the Sham group had a higher value(P<0.05)compared with the P-Sham group.Compared with the Model group,the value of the P-Model group was significantly reduced(P<0.05).The score at 7d was significantly lower than that of 1d and 3d(P<0.05).2.TTC staining: After cerebral ischemia and reperfusion for 7d,there were no infarcts in the P-Sham group and the Sham group,and the infarct area of Model was the largest,which was significantly larger than that of the P-Model group(P<0.05).3.HE staining: After cerebral ischemia reperfusion for 1d,3d,and 7d,the brain tissue structure of the P-Sham and the Sham groups was dense,the staining was uniform,the morphology of neurons was normal,the arrangement was neat,and there was no obvious pathological tissue damage;The brain tissue damage in the Model group was the most serious,the brain tissue structure was loose,the number of neurons significantly reduced,the arrangement disordered,and the cytoplasm of cells appeared vacuolization and degeneration-like changes.Compared with the Model group,the damage ischemic brain tissue in the P-Model group significantly improved,the degree of damage to the morphological structure of brain cells was less,the number of necrotic cells decreased,and the number of neurons survived increased.4.The content of ERRα and Irisin in blood: After cerebral ischemia reperfusion for 1d,3d and 7d,the level of ERRα and Irisin in blood of each group increased.At 1d,the blood ERRα content in the P-Sham group was higher than that in Sham group,but there was no statistical significance(P>0.05).The content of Irisin in blood in the P-Sham group was higher than that in Sham group,and there was statistically different between the two groups(P<0.05).At 3d,7d,the level of ERRα and Irisin in blood of P-Sham group was significantly higher than those of the Sham group(P<0.05);The content of ERRα and Irisin in blood of P-model group was significantly higher than those of the Model group(P<0.05).At 7d,the content of ERRαand Irisin in blood of each group was the highest,and significantly higher than that of 1d and 3d(P<0.05).5.Expression of BDNF/Neu N proteins in brain tissues: After cerebral ischemia reperfusion for 1d,3d and 7d,compared with the Sham group,the positive expression of BDNF/Neu N in ischemic brain tissues in the Sham group increased significantly(P<0.05).Compared with the Model group,the positive expression of BDNF/Ne UN in ischemic brain tissue in the P-Model group significantly increased(P<0.05).The positive expression of BDNF/Neu N in ischemic brain tissue peaked at 7d,and was significantly more than that of 1d and 3d(P<0.05).6.Expression of PGC-1α,FNDC5 and BDNF proteins in brain tissue:After cerebral ischemia reperfusion for 1d,3d and 7d,the expression of PGC-1α,FNDC5 and BDNF proteins in brain tissue of rats of each group increased gradually.At 1d,the expression of PGC-1α,FNDC5 and BDNF proteins in brain tissue of the P-Sham group was higher than that of the Sham group,but there was no statistical significance(P>0.05).The expression of PGC-1α,FNDC5 and BDNF in ischemic brain tissue of P-model group was significantly higher than that of Model group(P<0.05).At 3d,7d,the expression of PGC-1α,FNDC5 and BDNF in ischemic brain tissue of P-Sham group was significantly higher than that of the Sham group(P<0.05);The expression of PGC-1α,FNDC5 and BDNF in ischemic brain tissue of the P-model group was significantly higher than that of the Model group(P<0.05).The expression of PGC-1α,FNDC5 and BDNF in each group reached the peak at 7d,and was significantly higher than that of 1d and 3d(P<0.05).Conclusions:1.Exercise preconditioning can reduce the neurological damage in rats after cerebral ischemia/reperfusion,improve the degree of pathological damage of ischemic brain tissue,and enhance the ability of nerve repair in the brain.2.Exercise preconditioning can promote nerve neuroregeneration,reshape the neurological system network,and improve brain neurological function by regulating the PGC-1α/FNDC5/BDNF signaling pathway and related protein expression in rat brain tissue after cerebral ischemia/reperfusion.