PMID- 31369718 OWN - NLM STAT- MEDLINE DCOM- 20200923 LR - 20231213 IS - 1873-7544 (Electronic) IS - 0306-4522 (Linking) VI - 415 DP - 2019 Sep 1 TI - Over-Expression of TRPC6 via CRISPR Based Synergistic Activation Mediator in BMSCs Ameliorates Brain Injury in a Rat Model of Cerebral Ischemia/Reperfusion. PG - 147-160 LID - S0306-4522(19)30468-3 [pii] LID - 10.1016/j.neuroscience.2019.06.041 [doi] AB - Stroke is a major life-threatening and disabling disease with a restricted therapeutic approach. Bone marrow stromal cells (BMSCs) possess proliferative ability and a multi-directional differentiation potential, and secrete a range of trophic/growth factors that can protect neurons after cerebral ischemia/reperfusion. Transient receptor potential canonical (TRPC) is a family of non-selective channels permeable to Ca(2+), with several functions including neuronal survival. Over-expression of TRPC6, a subtype of the TRPC family, was shown to protect neurons against cerebral ischemia/reperfusion injury. However, it remains unclear whether over-expression of TRPC6 in BMSCs can further reduce brain injury after ischemia/reperfusion. In the present study, we report that over-expression of TRPC6 via a CRISPR-based synergistic activation mediator in BMSCs provided a greater reduction of brain injury in a rat model of ischemia/reperfusion. Further, the improved neurofunctional outcomes were associated with increased TRPC6 and brain derived neurotrophic factor expression levels. Overall, these data suggest that TRPC6 over-expressing BMSCs may be a promising therapeutic agent for ischemic stroke. CI - Copyright (c) 2019 IBRO. Published by Elsevier Ltd. All rights reserved. FAU - Li, Wenbin AU - Li W AD - Department of Neurology, First Clinical College of Harbin Medical University, Room 501, Building 3, 23 Youzheng Street, Harbin, Heilongjiang Province, 150001, People's Republic of China. FAU - Yang, Fan AU - Yang F AD - Department of Neurology, First Clinical College of Harbin Medical University, Room 501, Building 3, 23 Youzheng Street, Harbin, Heilongjiang Province, 150001, People's Republic of China. FAU - Gao, Jinxing AU - Gao J AD - Department of Neurology, First Clinical College of Harbin Medical University, Room 501, Building 3, 23 Youzheng Street, Harbin, Heilongjiang Province, 150001, People's Republic of China. FAU - Tang, Yushi AU - Tang Y AD - Department of Neurology, First Clinical College of Harbin Medical University, Room 501, Building 3, 23 Youzheng Street, Harbin, Heilongjiang Province, 150001, People's Republic of China. FAU - Wang, Jing AU - Wang J AD - Department of Neurology, First Clinical College of Harbin Medical University, Room 501, Building 3, 23 Youzheng Street, Harbin, Heilongjiang Province, 150001, People's Republic of China. FAU - Pan, Yujun AU - Pan Y AD - Department of Neurology, First Clinical College of Harbin Medical University, Room 501, Building 3, 23 Youzheng Street, Harbin, Heilongjiang Province, 150001, People's Republic of China. Electronic address: yujunpan@ems.hrbmu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190729 PL - United States TA - Neuroscience JT - Neuroscience JID - 7605074 RN - 0 (Bdnf protein, rat) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Creb1 protein, rat) RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (TRPC Cation Channels) RN - 0 (Trpc6 protein, rat) RN - 12634-43-4 (Spectrin) RN - EC 3.4.22.- (Calpain) SB - IM MH - Animals MH - Brain Ischemia/metabolism MH - Brain-Derived Neurotrophic Factor/metabolism MH - Calpain/metabolism MH - Cell Survival MH - Clustered Regularly Interspaced Short Palindromic Repeats MH - Cyclic AMP Response Element-Binding Protein/metabolism MH - Male MH - Mesenchymal Stem Cells MH - Models, Animal MH - Neurons/metabolism MH - Neuroprotection/*genetics MH - Rats MH - Rats, Wistar MH - Reperfusion Injury/*metabolism MH - Spectrin/metabolism MH - TRPC Cation Channels/genetics/*metabolism MH - Up-Regulation OTO - NOTNLM OT - BDNF OT - BMSCs OT - CRISPR OT - TRPC6 OT - ischemia/reperfusion EDAT- 2019/08/02 06:00 MHDA- 2020/09/24 06:00 CRDT- 2019/08/02 06:00 PHST- 2018/12/15 00:00 [received] PHST- 2019/06/26 00:00 [revised] PHST- 2019/06/27 00:00 [accepted] PHST- 2019/08/02 06:00 [pubmed] PHST- 2020/09/24 06:00 [medline] PHST- 2019/08/02 06:00 [entrez] AID - S0306-4522(19)30468-3 [pii] AID - 10.1016/j.neuroscience.2019.06.041 [doi] PST - ppublish SO - Neuroscience. 2019 Sep 1;415:147-160. doi: 10.1016/j.neuroscience.2019.06.041. Epub 2019 Jul 29.