PMID- 32165091 OWN - NLM STAT- MEDLINE DCOM- 20201027 LR - 20201027 IS - 1096-0945 (Electronic) IS - 0014-4800 (Linking) VI - 114 DP - 2020 Jun TI - HIF-1alpha/SDF-1/CXCR4 axis reduces neuronal apoptosis via enhancing the bone marrow-derived mesenchymal stromal cell migration in rats with traumatic brain injury. PG - 104416 LID - S0014-4800(19)30847-0 [pii] LID - 10.1016/j.yexmp.2020.104416 [doi] AB - Mesenchymal stromal injection is a promising therapy for traumatic brain injury (TBI). The aim of this study was to explore the effects of the HIF-1alpha/SDF-1/CXCR4 axis on neuron repair in TBI rats through improving the bone marrow-derived mesenchymalstromal cells (BMSCs) migration. TBI rat models were established. The rats were treated with exogenous SDF-1, and then the neuronal apoptosis in TBI rats was measured. BMSCs from rats were collected, and the roles of NF-kappaB p65 expression in nuclei, overexpression of SDF-1 and HIF-1alpha, as well as downregulation of CXCR4 in BMSC migration were identified. HIF-1alpha- and SDF-1- treated BMSCs were transplanted into TBI rats, after which the neuronal apoptosis and activity of the HIF-1alpha/SDF-1/CXCR4 axis were detected. Consequently, we found SDF-1 elevated the HIF-1alpha/SDF-1/CXCR4 activity and presented protective roles in TBI rat hippocampal neurons with reduced neuronal apoptosis. SDF-1 promoted BMSC migration in vitro, and co-effects of SDF-1 and HIF-1alpha showed strong promotion, while CXCR4 inhibition suppressed BMSC migration. BMSC transplantation activated the HIF-1alpha/SDF-1/CXCR4 axis and reduced neuronal apoptosis in TBI rats. To conclude, our study demonstrated that the HIF-1alpha/SDF-1/CXCR4 axis could enhance BMSC migration and alleviate neuronal damage and apoptosis in TBI rats. This study provided novel options for TBI therapy. CI - Copyright (c) 2020 Elsevier Inc. All rights reserved. FAU - Guo, Kai AU - Guo K AD - Department of Neurosurgery, Xingtai People's Hospital, Xingtai 054031, Hebei, PR China. FAU - Yao, Xinyu AU - Yao X AD - Department of Anesthesia, Xingtai People's Hospital, Xingtai 054031, Hebei, PR China. FAU - Wu, Weijing AU - Wu W AD - Department of Neurosurgery, Xingtai People's Hospital, Xingtai 054031, Hebei, PR China. FAU - Yu, Ziyi AU - Yu Z AD - Department of Intensive Care Unit,Tangshan Worker Hospital, Tangshan 063000, Hebei, PR China. FAU - Li, Zhenzhong AU - Li Z AD - Department of Neurosurgery, Xingtai People's Hospital, Xingtai 054031, Hebei, PR China. FAU - Ma, Zenglu AU - Ma Z AD - Department of Neurosurgery, Xingtai People's Hospital, Xingtai 054031, Hebei, PR China. FAU - Liu, Dengxiang AU - Liu D AD - Department of Radiotherapy, Xingtai People's Hospital, Xingtai 054031, Hebei, PR China. Electronic address: Liudengx0709@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200309 PL - Netherlands TA - Exp Mol Pathol JT - Experimental and molecular pathology JID - 0370711 RN - 0 (CXCL12 protein, rat) RN - 0 (Chemokine CXCL12) RN - 0 (Cxcr4 protein, rat) RN - 0 (Hif1a protein, rat) RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - 0 (Receptors, CXCR4) SB - IM MH - Animals MH - Apoptosis/genetics MH - Brain Injuries, Traumatic/*genetics/metabolism/pathology MH - Cell Movement/genetics MH - Chemokine CXCL12/*genetics MH - Disease Models, Animal MH - Hippocampus/metabolism/pathology MH - Humans MH - Hypoxia-Inducible Factor 1, alpha Subunit/*genetics MH - Mesenchymal Stem Cell Transplantation MH - Mesenchymal Stem Cells/metabolism/pathology MH - Neurons/metabolism/pathology MH - Rats MH - Receptors, CXCR4/*genetics MH - Signal Transduction/genetics MH - Stromal Cells/metabolism/pathology OTO - NOTNLM OT - Bone marrow-derived mesenchymalstromal cells OT - Chemotaxis cytokine receptor-4 OT - Hypoxia-inducible factor-1alpha OT - Neuronal apoptosis OT - Stromal cell-derived factor-l OT - Traumatic brain injury COIS- Declaration of Competing Interest The authors declare that they have no conflict of interest. EDAT- 2020/03/14 06:00 MHDA- 2020/10/28 06:00 CRDT- 2020/03/14 06:00 PHST- 2019/11/07 00:00 [received] PHST- 2020/02/21 00:00 [revised] PHST- 2020/03/07 00:00 [accepted] PHST- 2020/03/14 06:00 [pubmed] PHST- 2020/10/28 06:00 [medline] PHST- 2020/03/14 06:00 [entrez] AID - S0014-4800(19)30847-0 [pii] AID - 10.1016/j.yexmp.2020.104416 [doi] PST - ppublish SO - Exp Mol Pathol. 2020 Jun;114:104416. doi: 10.1016/j.yexmp.2020.104416. Epub 2020 Mar 9.