To observe the effects of electro-scalp acupuncture(ESA) on treating ischemic injury in the cortex of rats with ischemic stroke(IS).Methods:According to the random number table method，the rats were divided into the sham operation group，model group，ESA group，agonist group，inhibitor group，and ESA+inhibitor group，with 11 rats in each group.Except for the sham operation group，the rats in the remaining groups were employed to build the middle cerebral artery occlusion(MCAO) model.Six hours after successful modeling，the ESA group was treated with ESA with the intensity of 1 mA，and frequency of 2/100 Hz and 30 minutes per day.The agonist group was given intraperitoneal injection of PTEN-induced putative kinase 1(PINK1)/human Parkinson's protein 2(Parkin) pathway activator carbonylcyanide m-chlorophenylhydrazone(CCCP) solution at a dose of 4 mg/(kg·d) once a day.In the inhibitor group，intraperitoneal injection of Mdivi-1 solution was given at a dose of 2 mg/(kg·d) once a day，while the ESA+inhibitor group received intraperitoneal injection of Mdivi-1 solution and ESA therapy intervention for 30 minutes a day.The intervention was conducted in each group for seven consecutive days.Meanwhile，the mNSS method was adopted to assess the degree of neurological defects in rats，and the proportion of cerebral infarction volume in rats was measured by 2,3,5-triphenyl tetrazolium chloride(TTC) staining.The co-localization levels of TOM20 and LC3 in ischemic brain tissue were detected by fluorescence double staining，and the expressions of COX Ⅳ，PINK1，and Parkin in the ischemic cortical region of rats were compared by Western blotting.Results:Compared with the sham operation group，the mNSS score of rats in the model group was high(P<0.01)，while compared with the model group，the mNSS scores of the agonist and ESA groups were low(P<0.01)，and the mNSS score of the inhibitor group was high(P<0.01).Compared to the inhibitor group，the mNSS score of the ESA+inhibitor group was low(P<0.01).There was no statistically significant difference in mNSS scores between the ESA group and the agonist group(P>0.05).Compared with the sham operation group，the model group had a large cerebral infarction volume(P<0.01)，while compared with the model group，the agonist group，ESA group，and inhibitor group had small cerebral infarction volumes in rats(P<0.01，P<0.05).Compared with the inhibitor group，the ESA+inhibitor group had a small cerebral infarction volume(P<0.01)，and there was no statistical difference in the cerebral infarction volume between the ESA group and the agonist group(P>0.01).Compared with the sham operation group，the co-localization levels of TOM20 and LC3 in the ischemic cortex of the model group were lower(P<0.01).Compared with the model group，the co-localization levels of TOM20 and LC3 were higher in the ESA group and agonist group(P<0.01)，while the co-localization levels of TOM20 and LC3 were lower in the inhibitor group(P<0.01).Compared with the inhibitor group，the co-localization levels of TOM20 and LC3 were higher in the ESA+inhibitor group(P<0.01).There was no statistical difference in the co-localization levels of TOM20 and LC3 between the ESA group and the agonist group(P>0.05).Compared with the sham operation group，the expression level of COX Ⅳ in the model group was high(P<0.01)，while compared to the model group，the expression levels of COX Ⅳ in the ESA and agonist groups were low(P<0.05，P<0.01)，and the expression of COX Ⅳ in the inhibitor group was high(P<0.05).Compared with the inhibitor group，the expression level of COX Ⅳ in the ESA+inhibitor group was low(P<0.01)，with no statistical difference between the expression levels of COX Ⅳ in the ESA group and agonist group(P>0.05).Compared with the sham operation group，the expression of PINK1 and Parkin proteins in the ischemic cortex region of the rats in the model group was low(P<0.01)，while compared with the model group，the expression of PINK1 and Parkin proteins in the ischemic cortex region of the rats in the ESA and agonist groups was high(P<0.05，P<0.01)，with low expression of PINK1 and Parkin proteins in the ischemic cortex regions of rats in the inhibitor group(P<0.05).Compared with the inhibitor group，the expression levels of PINK1 and Parkin proteins in the ischemic cortex regions of rats in the ESA+inhibitor group were high(P<0.01)，with no statistical difference between the expression of PINK1 and Parkin proteins in the ischemic cortex regions of rats in the ESA group and agonist group(P>0.05).Conclusion:ESA can alleviate ischemic brain injury by activating the PINK1/Parkin signaling pathway-mediated mitophagy.