PMID- 28884834 OWN - NLM STAT- MEDLINE DCOM- 20190227 LR - 20190227 IS - 1097-4644 (Electronic) IS - 0730-2312 (Linking) VI - 119 IP - 6 DP - 2018 Jun TI - Transplantation of hypoxic preconditioned neural stem cells benefits functional recovery via enhancing neurotrophic secretion after spinal cord injury in rats. PG - 4339-4351 LID - 10.1002/jcb.26397 [doi] AB - Spinal cord injury (SCI) is a debilitating, costly, and common pathological condition that affects the function of central nervous system (CNS). To date, there are few promising therapeutic strategies available for SCI. To look for a suitable therapeutic strategy, we have developed a sublethal hypoxic preconditioning procedure using Fluorescence-activated cell sorting (FACS) analysis, LDH releasing, and cell viability assays in vitro. Meanwhile, we have examined the benefits of neural stem cells (NSCs) transplantation prior to hypoxic preconditioning on functional recovery and potential mechanism via MRI screening, H&E, and Nissl staining, immunofluorescence staining and Elisa assays. Our data showed that transplantation of hypoxic prconditioned NSCs could enhance neuronal survival, especially 5-TH(+) and ChAT(+) neurons, in the injured spinal cord to reinforce functional benefits. The hypoxia exposure upregulated HIF-1alpha, neurotrophic and growth factors including neurotrophin-3 (NT-3), glial cell-derived neurotrophic factor (GDNF), and brain-derived neurotrophic factor (BDNF) in vitro and in vivo. Furthermore, functional recovery, including locomotor and hypersensitivities to mechanical and thermal stimulation assessed via behavioral and sensory tests, improved significantly in rats with engraftment of NSCs after hypoxia exposure from day 14 post-SCI, compared with the control and N-NSCs groups. In short, the approach employed in this study could result in functional recovery via upregulating neurotrophic and growth factors, which implies that hypoxic preconditioning strategy could serve as an effective and feasible strategy for cell-based therapy in the treatment of SCI in rats. CI - (c) 2017 Wiley Periodicals, Inc. FAU - Fan, Wei-Li AU - Fan WL AD - Department of Spinal Surgery, Daping Hospital, Research Institute of Surgery, The Third Military Medical University, Chongqing, China. FAU - Liu, Peng AU - Liu P AD - Department of Spinal Surgery, Daping Hospital, Research Institute of Surgery, The Third Military Medical University, Chongqing, China. FAU - Wang, Guan AU - Wang G AD - Department of Spinal Surgery, Daping Hospital, Research Institute of Surgery, The Third Military Medical University, Chongqing, China. FAU - Pu, Jun-Gang AU - Pu JG AD - Department of Spinal Surgery, Daping Hospital, Research Institute of Surgery, The Third Military Medical University, Chongqing, China. FAU - Xue, Xin AU - Xue X AD - Department of Spinal Surgery, Daping Hospital, Research Institute of Surgery, The Third Military Medical University, Chongqing, China. FAU - Zhao, Jian-Hua AU - Zhao JH AUID- ORCID: 0000-0003-4393-4818 AD - Department of Spinal Surgery, Daping Hospital, Research Institute of Surgery, The Third Military Medical University, Chongqing, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180228 PL - United States TA - J Cell Biochem JT - Journal of cellular biochemistry JID - 8205768 RN - 0 (Nerve Growth Factors) SB - IM MH - Animals MH - Female MH - *Ischemic Preconditioning MH - *Locomotion MH - Nerve Growth Factors/*metabolism MH - Neural Stem Cells/*metabolism/pathology MH - Rats MH - Rats, Sprague-Dawley MH - *Recovery of Function MH - *Spinal Cord Injuries/metabolism/pathology/physiopathology/therapy MH - *Stem Cell Transplantation OTO - NOTNLM OT - hypoxic preconditioning OT - neural stem cells OT - neurotrophic factors OT - spinal cord injury EDAT- 2017/09/09 06:00 MHDA- 2019/02/28 06:00 CRDT- 2017/09/09 06:00 PHST- 2017/04/21 00:00 [received] PHST- 2017/08/30 00:00 [accepted] PHST- 2017/09/09 06:00 [pubmed] PHST- 2019/02/28 06:00 [medline] PHST- 2017/09/09 06:00 [entrez] AID - 10.1002/jcb.26397 [doi] PST - ppublish SO - J Cell Biochem. 2018 Jun;119(6):4339-4351. doi: 10.1002/jcb.26397. Epub 2018 Feb 28.