PMID- 28421542 OWN - NLM STAT- MEDLINE DCOM- 20190523 LR - 20210222 IS - 1559-1182 (Electronic) IS - 0893-7648 (Linking) VI - 55 IP - 3 DP - 2018 Mar TI - Neural Stem Cell Transplantation Promotes Functional Recovery from Traumatic Brain Injury via Brain Derived Neurotrophic Factor-Mediated Neuroplasticity. PG - 2696-2711 LID - 10.1007/s12035-017-0551-1 [doi] AB - Traumatic brain injury (TBI) induces cognitive impairments, motor and behavioral deficits. Previous evidences have suggested that neural stem cell (NSC) transplantation could facilitate functional recovery from brain insults, but their underlying mechanisms remains to be elucidated. Here, we established TBI model by an electromagnetic-controlled cortical impact device in the rats. Then, 5 mul NSCs (5.0 x 10(5)/mul), derived from green fluorescent protein (GFP) transgenic mouse, was transplanted into the traumatic brain regions of rats at 24 h after injury. After differentiation of the NSCs was determined using immunohistochemistry, neurological severity scores (NSS) and rotarod test were conducted to detect the neurological behavior. Western blot and RT-PCR as well as ELASA were used to evaluate the expression of synaptophysin and brain-derived neurotrophic factor (BDNF). In order to elucidate the role of BDNF on the neural recovery after NSC transplantation, BDNF knockdown in NSC was performed and transplanted into the rats with TBI, and potential mechanism for BDNF knockdown in the NSC was analyzed using microassay analysis. Meanwhile, BDNF antibody blockade was conducted to further confirm the effect of BDNF on neural activity. As a result, an increasing neurological function improvement was seen in NSC transplanted rats, which was associated with the upregulation of synaptophysin and BDNF expression. Moreover, transplantation of BDNF knockdown NSCs and BDNF antibody block reduced not only the level of synaptophysin but also exacerbated neurological function deficits. Microassay analysis showed that 14 genes such as Wnt and Gsk3-beta were downregulated after BDNF knockdown. The present data therefore showed that BDNF-mediated neuroplasticity underlie the mechanism of NSC transplantation for the treatment of TBI in adult rats. FAU - Xiong, Liu-Lin AU - Xiong LL AD - Institute of Neurological Disease, and Department of Anesthesiology, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, 610041, China. FAU - Hu, Yue AU - Hu Y AD - Institute of Neurological Disease, and Department of Anesthesiology, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, 610041, China. FAU - Zhang, Piao AU - Zhang P AD - Institute of Neuroscience, and Animal Zoology Department, Kunming Medical University, Kunming, 650500, China. FAU - Zhang, Zhuo AU - Zhang Z AD - Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xian, 710032, China. FAU - Li, Li-Hong AU - Li LH AD - Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xian, 710032, China. FAU - Gao, Guo-Dong AU - Gao GD AD - Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xian, 710032, China. FAU - Zhou, Xin-Fu AU - Zhou XF AD - Department of Human Physiology, Flinders University, GPO Box 2100, Adelaide, SA, 5001, Australia. FAU - Wang, Ting-Hua AU - Wang TH AD - Institute of Neurological Disease, and Department of Anesthesiology, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, 610041, China. tinghua_neuron@263.net. AD - Institute of Neuroscience, and Animal Zoology Department, Kunming Medical University, Kunming, 650500, China. tinghua_neuron@263.net. LA - eng GR - No. 2014BAI01B10/National Key Technology Research and Development Program of the Ministry of Science and Technology of China/International PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170418 PL - United States TA - Mol Neurobiol JT - Molecular neurobiology JID - 8900963 RN - 0 (Bdnf protein, rat) RN - 0 (Brain-Derived Neurotrophic Factor) SB - IM MH - Animals MH - Brain Injuries, Traumatic/*metabolism/*therapy MH - Brain-Derived Neurotrophic Factor/deficiency/*metabolism MH - Cells, Cultured MH - Female MH - Male MH - Mice MH - Mice, Knockout MH - Mice, Transgenic MH - Neural Stem Cells/*metabolism/*transplantation MH - Neuronal Plasticity/*physiology MH - Rats MH - Rats, Sprague-Dawley MH - Recovery of Function/physiology MH - Stem Cell Transplantation/*methods OTO - NOTNLM OT - Brain-derived neurotrophic factor OT - Neural stem cell transplantation OT - RNA knockdown OT - Synaptophysin OT - Traumatic brain injury EDAT- 2017/04/20 06:00 MHDA- 2019/05/24 06:00 CRDT- 2017/04/20 06:00 PHST- 2016/06/29 00:00 [received] PHST- 2017/04/07 00:00 [accepted] PHST- 2017/04/20 06:00 [pubmed] PHST- 2019/05/24 06:00 [medline] PHST- 2017/04/20 06:00 [entrez] AID - 10.1007/s12035-017-0551-1 [pii] AID - 10.1007/s12035-017-0551-1 [doi] PST - ppublish SO - Mol Neurobiol. 2018 Mar;55(3):2696-2711. doi: 10.1007/s12035-017-0551-1. Epub 2017 Apr 18.