〔Abstract〕 Objective To investigate the effect of glycogen synthase kinase 3β(GSK-3β) and its correlation with microtubule-associated protein 2(MAP2) during cerebral hypoxia/reoxygenation(H/R) in zebrafish. Methods The cerebral hypoxia/reoxygenation model of zebrafish was established. Healthy adult zebrafishes of the same size were divided into control group( Control),hypoxia/reoxygenation group( H/R) and hypoxia/reoxygenation +GSK-3β inhibitor group( H/R + TDZD-8) for experiment. The brain tissues of zebrafish in each group were selected to determine the mRNA expressions of hypoxia inducible factor 1αa and 1αb( Hi F-1αa and HIF-1αb) at different reoxygenation time points by qRT-PCR,and the protein expression levels of HIF-1α,GSK-3β,p-GSK-3β( Ser9) and MAP2 were detected by Western blot,TTC staining and TUNEL staining were used to detect cerebral infarction area and cell apoptosis,and immunofluorescence was used to detect the distribution and expression of MAP2 in brain. Results Compared with Control group,the mRNA levels of Hif-1αa and Hif-1αb( P<0. 01) and protein expression of Hif-1α( P<0. 01) increased in H/R group,the area of cerebral infarction( P<0. 01) and apoptotic cells( P<0. 01) increased,p-GSK-3 β( Ser 9)/GSK-3β ratio,MAP2 protein expression( P<0. 05)and immunofluorescence expression of MAP2( P<0. 01) reduced; Furthermore,TDZD-8 pretreatment could relieve the brain injury of H/R zebrafish by decreasing the infarct size and cell apoptosis,improving the ratio of pGSK-3β( Ser 9)/GSK-3β,and increasing the expression of MAP2. Conclusion Hypoxia/reoxygenation can cause brain neuron damage in zebrafish,and its mechanism may be related to inhibition of GSK-3β phosphorylation and MAP2 expression. GSK-3β specific inhibitor TDZD-8 can reverse the damage of brain neurons caused by hypoxia/reoxygenation by promoting the expression of P-GSK-3 β( Ser 9) and reducing MAP2 degradation.