Role of ERK in S1PR1-mediated proliferation of hippocampal stem cells following traumatic brain injury: An experimental study

Abstract

Objective To explore the role of extracellular signal regulated protein kinase (ERK) in sphingosine-1-phosphate receptor 1 (S1PR1)-mediated neural stem cell (NSC) proliferation in hippocampus following traumatic brain injury (TBI). Methods Rat model of TBI was induced by a controlled cortical impact device. A total of 112 Sprague Dawley rats were randomly and evenly divided into sham, TBI, TBI+ VPC and TBI+ U0126 groups according to random number table. Rats in TBI+ VPC group received 7 intraperitoneal injections of VPC23019 (S1PR1 antagonist) at scheduled time points following TBI. Rats in TBI+ U0126 group were intravenously administrated with U0126 (ERK inhibitor) via tail vein at 20 min before TBI. The levels of S1PR1, phosphate ERK (pERK) and total ERK (tERK) in hippocampus were determined by Western blot. NSC proliferation in subgranular zone of hippocampus was assessed by double-labeled immunofluorescence. Results Compared with sham group, the expressions of hippocampal S1PR1 and pERK in TBI group were significantly increased, and the proliferation of NSCs in subgranular zone was activated at 7, 14 and 21 days after TBI (all P 0.05). In addition, the difference in tERK expression between the 4 groups was not statistically significant (all P>0.05). Conclusions Increased S1PR1 could trigger up-regulation of pERK expression and enhance NSC proliferation in hippocampus after TBI. Inhibition of ERK cascade could prevent S1PR1-mediated NSC proliferation in hippocampus. It is suggested that S1PR1 might regulate the proliferation of endogenous NSCs via ERK signaling pathway post trauma. Key words: Craniocerebral trauma; Neural stem cells; Cell proliferation; Rats; Extracellular signal-regulated kinases