Transplantation with hypoxia‐preconditioned mesenchymal stem cells suppresses brain injury caused by cardiac arrest–induced global cerebral ischemia in rats

• Published in: Journal of neuroscience research Vol. 95; no. 10; pp. 2059 - 2070
• Main Authors: Wang, Ji‐wen, Qiu, Yu‐ru, Fu, Yue, Liu, Jun, He, Zhi‐Jie, Huang, Zi‐tong
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.10.2017
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Animals; Bone marrow; Bone marrow transplantation; Brain; Brain Injuries - etiology; Brain Injuries - pathology; Brain injury; Brain Ischemia - etiology; Brain Ischemia - pathology; Brain stem; Cardiac arrest; Cerebral blood flow; cerebral ischemia; CXC chemokines; CXCR4; Differentiation; Emergency medical care; Emergency medical services; Head injuries; Heart Arrest - complications; Heart diseases; HIF; Hypoxia; Hypoxia-inducible factor 1; Hypoxia-inducible factors; Integration; Ischemia; Ischemic Preconditioning - methods; Leukocyte migration; Male; mesenchymal stem cell; Mesenchymal Stem Cell Transplantation - methods; Mesenchymal stem cells; Mesenchyme; migration; Neurological complications; PI3K/AKT pathway; rat; Rats; Rats, Sprague-Dawley; Stem cells; Stroke; Transplantation; Traumatic brain injury; hypoxia; mesenchymal stem cell; HIF; rat; cerebral ischemia; transplantation; migration; CXCR4; cardiac arrest; PI3K/AKT pathway
• ISSN: 0360-4012; 1097-4547
• DOI: 10.1002/jnr.24025

Cardiac arrest–induced global cerebral ischemia is a main cause of neurological dysfunction in emergency medicine. Transplantation with bone marrow mesenchymal stem cells (MSCs) has been used in stroke models to repair the ischemic brain injury, but it is little studied in models with global cerebral ischemia. In the present study, a hypoxia precondition was used to improve the efficacy of MSC transplantation, given the low survival and migration rates and limited differentiation capacities of MSCs. We found that hypoxia can increase the expansion and migration of MSCs by activating the PI3K/AKT and hypoxia‐inducible factor‐1α/CXC chemokine receptor‐4 pathways. By using a cardiac arrest–induced global cerebral ischemic model in rats, we found that transplantation of hypoxia‐preconditioned MSCs promoted the migration and integration of MSCs and decreased neuronal death and inflammation in the ischemic cortex. © 2017 Wiley Periodicals, Inc. Hypoxia at 1% O2 increases the expansion and migration of MSCs by activating the PI3K/ AKT and hypoxia‐inducible factor‐1a/CXC chemokine receptor‐4 pathways. Transplantation of hypoxia‐preconditioned MSCs promotes the migration and integration of MSCs and decreased neuronal death and inflammation in the ischemic cortex.