Kainic acid (KA) induces hippocampal cell death and astrocyte proliferation. There are reports that sphingosine kinase (SPHK)1 and sphingosine-1-phosphate (SIP) receptor 1 (S1P(1)) signaling axis controls astrocyte proliferation. Here we examined the temporal changes of SPHIMS1P(1) in mouse hippocampus during KA-induced hippocampal cell death. Mice were killed at 2, 6, 24, or 48 h after KA (30 mg/kg) injection. There was an increase in Fluoro-Jade B-positive cells in the hippocampus of KA-treated mice with temporal changes of glial fibrillary acidic protein (GFAP) expression. The lowest level of SPHK1 protein expression was found 2 h after KA treatment. Six hours after KA treatment, the expression of SPHK1 and S1P1 proteins steadily increased in the hippocampus. In immunohistochemical analysis, SPHK1 and SIP, are more immunoreactive in astrocytes within the hippocampus of KA-treated mice than in hippocampus of control mice. These results indicate that SPHK1/S1P1 signaling axis may play an important role in astrocytes proliferation during KA-induced excitotoxicity. (C) 2010 Elsevier Inc. All rights reserved.