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 upregulated by 66.67％ in TBI + SEW group and down-regulated by 20.29％ in TBI + VPC group (P ＜0.05).The nmmber 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 S1 PRI is closely associated with the proliferation of NSCs in hippocampus after TBI,indicating that S1PR1 activation may be an effective strategy to improve the posttraumatic neurogenesis.

BACKGROUND:Stem cells have been widely used in the treatment of spinal cord injury,but the clinical application is limited by immune rejection,difficulty in cell harvesting and purification.However,human nasal mucosa mesenchymal stem cells (hNM-MSCs) have no such problems,and its clinical application in the treatment of spinal cord injury has been not reported yet.OBJECTIVE:To observe the biological characteristics of autologous hNM-MSCs and its clinical efficacy in the treatment of advanced incomplete spinal cord injury.METHODS:NM-MSCs were isolated from the human nasal mucosa,cultured and identified in vitro.The ultrastructure of NM-MSCs was observed by transmission electron microscope and scanning electron microscope.Then the NM-MSCs were induced to differentiate into osteocytes,adipocytes,stem cell spheres,or neurons in vitro.Totally eight patients with incomplete spinal cord injury were enrolled and subjected to hNM-MSCs transplantation via lumbar puncture for 1-3 sessions of about 5× 107 cells each,with an interval of 5-7 days,after the approval of the medical ethics committee.All the patients were followed up for 6 months.Preoperative and postoperative therapeutic effect evaluations were performed on the basis of American Spinal Injury Association (ASIA) scores.RESULTS AND CONCLUSION:Under light microscope,the NM-MSCs were mainly spindle-shaped,positive for STRO-1 and exhibited a radial arrangement.NM-MSCs highly expressed CD73,CD90 and CD105,but did not express CD34 and CD45,with the purity of over 97％.And lots of podgy microvilli were seen on the surface of NM-MSCs under the scanning electron microscope,and two kinds of cell morphologies were seen under the transmission electron microscope.Moreover,hNM-MSCs had the ability to differentiate into osteocytes,adipocytes,stem cell spheres and neurons.During the 6-month follow-up,seven patients achieved neurological function recovery to different extents except for one patient,and no side effects were found.It is concluded that hNM-MSCs can become the ideal seed cells for tissue-engineered cell repair.Autologous NM-MSCs transplantation for the treatment of spinal cord injury can achieve the ideal effect,with the value of clinical application.