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Subarachnoid Hemorrhage Promotes Proliferation, Differentiation, and Migration of Neural Stem Cells via BDNF Upregulation.

ABSTRACT: Patients who suffer from subarachnoid hemorrhage (SAH) usually have long-term neurological impairments. Endogenous neurogenesis might play a potential role in functional recovery after SAH; however, the underlying neurogenesis mechanism is still unclear. We assessed the extent of neurogenesis in the subventricular zone (SVZ) to better understand the neurogenesis mechanism after SAH. We performed a rat model of SAH to examine the extent of neurogenesis in the SVZ and assessed functional effects of the neurotrophic factors in the cerebrospinal fluid (CSF) on neural stem cells (NSCs) after SAH. In this study, the proliferation, differentiation, and migratory capacities of NSCs in the SVZ were significantly increased on days 5 and 7 post SAH. Furthermore, treatment of cultured rat fetal NSCs with the CSF collected from rats on days 5 and 7 post SAH enhanced their proliferation, differentiation, and migration. Enzyme-linked immunosorbent assay (ELISA) of the CSF detected a marked increase in the concentration of brain-derived neurotrophic factor (BDNF). Treating the cultured NSCs with recombinant BDNF (at the same concentration as that in the CSF) or with CSF from SAH rats, directly, stimulated proliferation, differentiation, and migration to a similar extent. BDNF expression was upregulated in the SVZ of rats on days 5 and 7 post SAH, and BDNF release occurred from NSCs, astrocytes, and microglia in the SVZ. These results indicate that SAH triggers the expression of BDNF, which promotes the proliferation, differentiation, and migration of NSCs in the SVZ after SAH.

SUBMITTER: Lee WD

PROVIDER: S-EPMC5104421 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Subarachnoid Hemorrhage Promotes Proliferation, Differentiation, and Migration of Neural Stem Cells via BDNF Upregulation.

Lee Wen-Di WD Wang Kuo-Chuan KC Tsai Yi-Fen YF Chou Pin-Chun PC Tsai Li-Kai LK Chien Chung-Liang CL

PloS one 20161110 11

Patients who suffer from subarachnoid hemorrhage (SAH) usually have long-term neurological impairments. Endogenous neurogenesis might play a potential role in functional recovery after SAH; however, the underlying neurogenesis mechanism is still unclear. We assessed the extent of neurogenesis in the subventricular zone (SVZ) to better understand the neurogenesis mechanism after SAH. We performed a rat model of SAH to examine the extent of neurogenesis in the SVZ and assessed functional effects o ...[more]

PMID: 27832087

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Project description:Repetitive transcranial magnetic stimulation (rTMS) is a physical treatment applied during recovery after intracerebral hemorrhage (ICH). With in vivo and in vitro assays, the present study sought to investigate how rTMS influences neural stem cells (NSCs) after ICH and the possible mechanism. Following a collagenase-induced ICH, adult male C57BL/6 J mice were subjected to rTMS treatment every 24 h for 5 days using the following parameters: frequency, 10 Hz; duration, 2 s; wait time, 5.5 s; 960 trains (500 µV/div, 5 ms/div, default setting). Brain water content and neurobehavioral score were assessed at days 1, 3, and 5 after ICH. The proliferation and differentiation of NSCs were observed using immunofluorescence staining for Nestin, Ki-67, DCX, and GFAP on day 3 after ICH, and rTMS treatment with the same parameters was applied to NSCs in vitro. We found that rTMS significantly reduced brain edema and alleviated neural functional deficits. The mice that underwent ICH recovered faster after rTMS treatment, with apparent proliferation and neuronal differentiation of NSCs and attenuation of glial differentiation and GFAP aggregation. Accordingly, proliferation and neuronal differentiation of isolated NSCs were promoted, while glial differentiation was reduced. In addition, microarray analysis, western blotting assays, and calcium imaging were applied to initially investigate the potential mechanism. Bioinformatics showed that the positive effect of rTMS on NSCs after ICH was largely related to the MAPK signaling pathway, which might be a potential hub signaling pathway under the complex effect exerted by rTMS. The results of the microarray data analysis also revealed that Ca2+ might be the connection between physical treatment and the MAPK signaling pathway. These predictions were further identified by western blotting analysis and calcium imaging. Taken together, our findings showed that rTMS after ICH exhibited a restorative effect by enhancing the proliferation and neuronal differentiation of NSCs, potentially through the MAPK signaling pathway.

Dataset Information

Subarachnoid Hemorrhage Promotes Proliferation, Differentiation, and Migration of Neural Stem Cells via BDNF Upregulation.

Publications

Subarachnoid Hemorrhage Promotes Proliferation, Differentiation, and Migration of Neural Stem Cells via BDNF Upregulation.

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