To sum up, ERK1/2 inhibitor PD98059 maintained mitochondrial balance by the upregulated Mfn1/2 and OPA1 and downregulated p-ERK1/2, p-Drp-1 and Fis1, suggesting that hyperglycemia worsened celebral I/R induced brain damage via ERK1/2 activated mitochondrial fission. Here, MAPK3 is linked to Hyperglycemia.