Effects of sphingosine-1-phosphate receptor 1 alteration on proliferation of neural stem cells in hippocampus after traumatic brain injury

Abstract

Objective To investigate the effects of sphingosine-1- phosphate receptor 1 (S1PR1) changes on the proliferation of endogenous neural stem cells (NSCs) in hippocampus after traumatic brain injury (TBI). Methods Rat TBI models were constructed by the means of controlled cortical injury. A total of 72 rats were included and randomly divided into four groups: sham, TBI, TBI+ SEW (TBI+ S1PR1 agonist SEW2871 intervention) and TBI+ VPC group (TBI+ S1PR1 antagonist VPC23019 intervention), with 18 rats per group. The TBI model was induced by a control cortical injury device. The injured rats in TBI+ SEW group and TBI+ VPC group were respectively administrated with S1PR1 agonist SEW2871 and antagonist VPC23019 at scheduled time points after TBI. Hippocampal S1PR1 expression was detected by Western-blotting and the proliferation of NSCs was assessed by double-labeled immunofluorescence staining at days 7, 14 and 21 after injury. Results At days 7, 14 and 21 after TBI, the hippocampal S1PR1 levels and NSCs proliferation amounts in sham, TBI, TBI+ SEW and TBI+ VPC groups were evidently different (P<0.05). In particular, the outstanding changes among the four groups above occurred at 7 d after injury were as following: S1PR1 expression in TBI group significantly increased by 1.56 times compared with that in sham group, and it was respectively up-regulated by 66.67% in TBI+ SEW group and down-regulated by 20.29% in TBI+ VPC group (P<0.05). The number of NSCs proliferation in TBI group was 2.08 times more than that in sham group, and it increased by 36.75% in TBI+ SEW group and reduced by 18.77% in TBI+ VPC group(P<0.05). Conclusion The expression of S1PR1 is closely associated with the proliferation of NSCs in hippocampus after TBI, indicating that S1PR1 activation may be an effective strategy to improve the post-traumatic neurogenesis. Key words: Brain injuries; Neural stem cells; Nerve regeneration; Sphingosine-1-phosphate receptor 1