OBJECTIVE To study histamine’s effect on longterm injuryafter cerebral ischemia,including on glial scar formation.METHODS After 90 min of transient middle cerebral artery occlusion(tMCAO),histidine with dose combination,500500 mg·kg-1,1000-500 mg·kg-1,1000-1000 mg·kg-1,10000 mg·kg-1(the first week and the later weeks were divided as two phases),was given to SD rats at 0 h,6 h and every other days after reperfusion.28 and 56 d after reperfusion,rats were evaluated with behavioral tests,such as neurological score,fear conditioning test,and Morris water maze.7,14,28,56 days after tMCAO,rats were transcardially perfused by 0.9% cold saline and 4% paraformaldehyde.The dissected brains were then cut into 10 m coronal sections and immunostained for GFAP,Ne-uN,and toluidine blue.Wound-healing assay in vitro was taken to study the promotion ofastrocyte migration provided by histamine.RESULTS After 28 d and 56 d of reperfusion,neurological scores,and learning and memory functions in fear conditioning test and Morris water maze significantly improved in histidine 1000-500 mg·kg-1 group.Meanwhile,the infract area and the glial scar area in this group also decreased.The reactive astrocytes(GFAP positive cells) area were closer to the infract core in the 1000-500 mg·kg-1 group than other groups at 14 d after reperfusion,however,there’s no difference at 7 d after operation.The shape of glial scar’s boundary of 1000-500 mg·kg-1 group was rougher than other groups and the polarizing ratio of astrocytes increased nearly two folds,which suggests the promotion of astrocyte migration by histamine.To our surprise,in the area where astrocyte migrated before,the number of neurons(NeuN positive cells) was up-regulated.In wound-healing assay,histamine promoted astrocyte migration at dose 0.1 μmol·L-1.Its promotion effect can be antagonized by H2 receptor antagonists cimetidine and famotidine,and can be reversed by Rp-cAMP,a PKA antagonist.CONCLUSION Histamine has protective effect on the long-term injury after cerebral ischemia.Its mechanism may involve the promotion of reactive astrocyte migration and subsequently neuron recovery through H2 receptor. OBJECTIVE To study histamine’s effect on longterm injury after cerebral ischemia, including on glial scar formation. METHODS After 90 min of transient middle cerebral artery occlusion (tMCAO), histidine with dose combination, 500500 mg · kg -1, 000-500 mg · kg- 1,1000-1,000 mg · kg -1,10000 mg · kg -1 (the first week and the later weeks were divided as two phases), was given to SD rats at 0 h, 6 h and every other days after reperfusion. 28 and 56 days after reperfusion, rats were evaluated with behavioral tests, such as neurological score, fear conditioning test, and Morris water maze.7, 14, 28, 56 days after tMCAO, rats were transcardially perfused by 0.9% cold saline and 4 % paraformaldehyde.The dissected brains were then cut into 10 m coronal sections and immunostained for GFAP, Ne-uN, and toluidine blue. Wound-healing assay in vitro was taken to study the promotion of astrocyte migration provided by histamine. RESULTS After 28 d and 56 d of reperfusion, neurological scores, and learning and memory functions in fear con ditioning test and Morris water maze significantly improved in histidine 1000-500 mg · kg-1 group. While the infract area and the glial scar area in this group also decreased. reactivegasy matrigel (GFAP positive cells) area were closer to the infract core in the 1000-500 mg · kg-1 group than the other groups at 14 d after reperfusion, however, there’s no difference at 7 d after operation. The shape of glial scar’s boundary of 1000-500 mg · kg -1 group was rougher than other groups and the polarizing ratio of astrocytes increased nearly two folds, which suggests the promotion of astrocyte migration by histamine. To our surprise, in the area where astrocyte migrated before, the number of neurons (NeuN positive cells) was up-regulated. In wound-healing assay, histamine promoted astrocyte migration at dose 0.1 μmol·L-1.Its promotion effect can be antagonized by H2 receptor antagonists cimetidine and famotidine, and can be reversed by Rp-cAMP, a PKA antagonist. CONCLUSION Histamine has protective effect o n the long-term injury after cerebral ischemia. Its mechanism may involve the promotion of reactive astrocyte migration and subsequent neuron recovery through H2 receptor.