Résumé
Objective To investigate the proliferative capacity of neural stem cells (NSCs) in rat hippocampus after traumatic brain injury (TBI) and its relationship with Janus kinase 2/signaling and transcriptional activation factor 3 (JAK2/STAT3) signaling pathway activity.Methods A total of 108 SD rats were randomly divided into control group (36 rats) and TBI group (72 rats).The TBI model was constructed by PinPointTM Precision Cortical Impactor.At 1,3,7,14,21 and 28 days after injury,the brain tissues were taken for immunofluorescence staining to detect the proliferation of NSCs [5-bromodeoxyuridine (BrdU) +/stem cell key protein-2 (Sox2) +] in hippocampus,and phosphorylated JAK2 (p-JAK2) and phosphorylated STAT3 (p-STAT3) were detected by Western blot.The expression level of p-JAK2 and p-STAT3 as well as the changing trend were analyzed.On the basis of preliminary analysis of the proliferation of NSCs and the change of JAK2/STAT3 signaling pathway activity in hippocampus,another 24 SD rats were randomly divided into TBI + normal saline group and TBI +AG490 (JAK2 specific inhibitor) group,with 12 rats in each group.At 7 days after injury,the proliferation of NSCs in hippocampus was detected by immunofluorescence staining,and the expression levels of p-JAK2 and p-STAT3 were detected by Western blot,so as to further confirm the correlation between the proliferation ability of NSCs in hippocampus and JAK2/STAT3 signaling pathway.Results Compared with the control group,the number of NSCs in the hippocampus of the TBI group and the expression of p-JAK2 and p-STAT3 increased.And the most significant increase occurred at 7 days after injury [number of NSCs:31.2 ± 4.7 in the control group,111.4 ± 8.1 in the TBI group (P ＜ 0.01);p-JAK2:1.11 ± 0.09 in the control group,2.16 ± 1.01 in the TBI group (P ＜ 0.01);p-STAT3:1.05 ± 0.06 in the control group and 2.06 ± 0.09 in the TBI group (P ＜ 0.01)].The proliferation of NSCs in hippocampus of TBI group was consistent with the change of p-JAK2 and p-STAT3 expression.Seven days after injury,the expression levels of p-JAK2 and p-STAT3 and the proliferation ability of NSCs in the TBI + AG490 were significantly decreased [p-JAK2:2.18 ± 0.15 in the TBI + isotonic saline group,1.24 ±0.10 in the TBI + AG490 group (P ＜0.01);p-STAT3:2.21 ±0.12 in the TBI + isotonic saline group,1.25 ± 0.11 in the TBI + AG490 group (P ＜ 0.01);NSCs number:112.8 ± 8.6 in the TBI + isotonic saline group,75.5 ± 6.4 in the TBI + AG490 group (P ＜ 0.05)].Conclusions The proliferation of NSCs in hippocampus of rats increased after TBI,and the activity of JAK2/STAT3 signaling pathway also increased,following the same trend.JAK2 inhibitor AG490 can reduce the activity of JAK2/STAT3 signaling pathway and the proliferation of NSCs.This can provide reference for researches on TBI promoting nerve regeneration and function repair.
Résumé
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.
Résumé
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.
Résumé
A case of lymphoepithelial was reported and the literature were reviewed. Early surgical treatment can help to get the better prognosis. There is currently no effective treatment methods and the disease have no lethal tendency. The early surgical treatment is recommended for its possibility of canceration.