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Glial scar formation resulted from excessive astrogliosis limits axonal regeneration and impairs recovery of function,thus an intervention to ameliorate excessive astrogliosis is crucial for the recovery of neurological function after cerebral ischemia.In this study we investigated the effects of caosine,an endogenous water-soluble dipeptide (β-alanyl-L-histidine),on astrogliosis of cells exposed to oxygen-glucose deprivation/recovery (OGD/R) in vitro.Primary cultured rat astrocytes exhibited a significant increase in proliferation at 24 h recovery after OGD for 2 h.Pretreatment with caosine (5 mmol/L) caused G1 arrest of reactive astrocytes,significantly attenuated OGD/R-induced increase in cyclin D1 protein expression and suppressed OGD/R-induced proliferation of reactive astrocytes.Caosine treatment also reversed glycolysis and ATP production,which was elevated at 24 h recovery after OGD.A marked increase in migration of reactive astrocytes was observed at 24 h after OGD,whereas caosine treatment reversed the expression levels of MMP-9 and suppressed the migration of astrocytes.Furthermore,caosine also improved neurite growth of cortical neurons co-cultured with astrocytes under ischemic conditions.These results demonstrate that caosine may be a promising candidate for inhibiting astrogliosis and promoting neurological function recovery after ischemic stroke.