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Ginkgolide B promotes the proliferation and differentiation of neural stem cells following cerebral ischemia/reperfusion injury, both in vivo and in vitro

Neural stem cells have great potential for the development of novel therapies for nervous system diseases. However, the proliferation of endogenous neural stem cells following brain ischemia is insufficient for central nervous system self-repair. Ginkgolide B has a robust neuroprotective effect. In...

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Autores principales: Zheng, Pei-Dong, Mungur, Rajneesh, Zhou, Heng-Jun, Hassan, Muhammad, Jiang, Sheng-Nan, Zheng, Jie-Sheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Medknow Publications & Media Pvt Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6065216/
https://www.ncbi.nlm.nih.gov/pubmed/30028328
http://dx.doi.org/10.4103/1673-5374.232476
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author Zheng, Pei-Dong
Mungur, Rajneesh
Zhou, Heng-Jun
Hassan, Muhammad
Jiang, Sheng-Nan
Zheng, Jie-Sheng
author_facet Zheng, Pei-Dong
Mungur, Rajneesh
Zhou, Heng-Jun
Hassan, Muhammad
Jiang, Sheng-Nan
Zheng, Jie-Sheng
author_sort Zheng, Pei-Dong
collection PubMed
description Neural stem cells have great potential for the development of novel therapies for nervous system diseases. However, the proliferation of endogenous neural stem cells following brain ischemia is insufficient for central nervous system self-repair. Ginkgolide B has a robust neuroprotective effect. In this study, we investigated the cell and molecular mechanisms underlying the neuroprotective effect of ginkgolide B on focal cerebral ischemia/reperfusion injury in vitro and in vivo. Neural stem cells were treated with 20, 40 and 60 mg/L ginkgolide B in vitro. Immunofluorescence staining was used to assess cellular expression of neuron-specific enolase, glial fibrillary acid protein and suppressor of cytokine signaling 2. After treatment with 40 and 60 mg/L ginkgolide B, cells were large, with long processes. Moreover, the proportions of neuron-specific enolase-, glial fibrillary acid protein- and suppressor of cytokine signaling 2-positive cells increased. A rat model of cerebral ischemia/reperfusion injury was established by middle cerebral artery occlusion. Six hours after ischemia, ginkgolide B (20 mg/kg) was intraperitoneally injected, once a day. Zea Longa’s method was used to assess neurological function. Immunohistochemistry was performed to evaluate the proportion of nestin-, neuron-specific enolase- and glial fibrillary acid protein-positive cells. Real-time quantitative polymerase chain reaction was used to measure mRNA expression of brain-derived neurotrophic factor and epidermal growth factor. Western blot assay was used to analyze the expression levels of brain-derived neurotrophic factor and suppressor of cytokine signaling 2. Ginkgolide B decreased the neurological deficit score, increased the proportion of nestin-, neuron-specific enolase- and glial fibrillary acid protein-positive cells, increased the mRNA expression of brain-derived neurotrophic factor and epidermal growth factor, and increased the expression levels of brain-derived neurotrophic factor and suppressor of cytokine signaling 2 in the ischemic penumbra. Together, the in vivo and in vitro findings suggest that ginkgolide B improves neurological function by promoting the proliferation and differentiation of neural stem cells in rats with cerebral ischemia/reperfusion injury.
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spelling pubmed-60652162018-08-09 Ginkgolide B promotes the proliferation and differentiation of neural stem cells following cerebral ischemia/reperfusion injury, both in vivo and in vitro Zheng, Pei-Dong Mungur, Rajneesh Zhou, Heng-Jun Hassan, Muhammad Jiang, Sheng-Nan Zheng, Jie-Sheng Neural Regen Res Research Article Neural stem cells have great potential for the development of novel therapies for nervous system diseases. However, the proliferation of endogenous neural stem cells following brain ischemia is insufficient for central nervous system self-repair. Ginkgolide B has a robust neuroprotective effect. In this study, we investigated the cell and molecular mechanisms underlying the neuroprotective effect of ginkgolide B on focal cerebral ischemia/reperfusion injury in vitro and in vivo. Neural stem cells were treated with 20, 40 and 60 mg/L ginkgolide B in vitro. Immunofluorescence staining was used to assess cellular expression of neuron-specific enolase, glial fibrillary acid protein and suppressor of cytokine signaling 2. After treatment with 40 and 60 mg/L ginkgolide B, cells were large, with long processes. Moreover, the proportions of neuron-specific enolase-, glial fibrillary acid protein- and suppressor of cytokine signaling 2-positive cells increased. A rat model of cerebral ischemia/reperfusion injury was established by middle cerebral artery occlusion. Six hours after ischemia, ginkgolide B (20 mg/kg) was intraperitoneally injected, once a day. Zea Longa’s method was used to assess neurological function. Immunohistochemistry was performed to evaluate the proportion of nestin-, neuron-specific enolase- and glial fibrillary acid protein-positive cells. Real-time quantitative polymerase chain reaction was used to measure mRNA expression of brain-derived neurotrophic factor and epidermal growth factor. Western blot assay was used to analyze the expression levels of brain-derived neurotrophic factor and suppressor of cytokine signaling 2. Ginkgolide B decreased the neurological deficit score, increased the proportion of nestin-, neuron-specific enolase- and glial fibrillary acid protein-positive cells, increased the mRNA expression of brain-derived neurotrophic factor and epidermal growth factor, and increased the expression levels of brain-derived neurotrophic factor and suppressor of cytokine signaling 2 in the ischemic penumbra. Together, the in vivo and in vitro findings suggest that ginkgolide B improves neurological function by promoting the proliferation and differentiation of neural stem cells in rats with cerebral ischemia/reperfusion injury. Medknow Publications & Media Pvt Ltd 2018-07 /pmc/articles/PMC6065216/ /pubmed/30028328 http://dx.doi.org/10.4103/1673-5374.232476 Text en Copyright: © Neural Regeneration Research http://creativecommons.org/licenses/by-nc-sa/4.0 This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.
spellingShingle Research Article
Zheng, Pei-Dong
Mungur, Rajneesh
Zhou, Heng-Jun
Hassan, Muhammad
Jiang, Sheng-Nan
Zheng, Jie-Sheng
Ginkgolide B promotes the proliferation and differentiation of neural stem cells following cerebral ischemia/reperfusion injury, both in vivo and in vitro
title Ginkgolide B promotes the proliferation and differentiation of neural stem cells following cerebral ischemia/reperfusion injury, both in vivo and in vitro
title_full Ginkgolide B promotes the proliferation and differentiation of neural stem cells following cerebral ischemia/reperfusion injury, both in vivo and in vitro
title_fullStr Ginkgolide B promotes the proliferation and differentiation of neural stem cells following cerebral ischemia/reperfusion injury, both in vivo and in vitro
title_full_unstemmed Ginkgolide B promotes the proliferation and differentiation of neural stem cells following cerebral ischemia/reperfusion injury, both in vivo and in vitro
title_short Ginkgolide B promotes the proliferation and differentiation of neural stem cells following cerebral ischemia/reperfusion injury, both in vivo and in vitro
title_sort ginkgolide b promotes the proliferation and differentiation of neural stem cells following cerebral ischemia/reperfusion injury, both in vivo and in vitro
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6065216/
https://www.ncbi.nlm.nih.gov/pubmed/30028328
http://dx.doi.org/10.4103/1673-5374.232476
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