title: Bone marrow stromal cells promote neuroplasticity of cerebral ischemic rats via a phosphorylated CRMP2-mediated mechanism.
abstract: Collapsin response mediator protein 2 (CRMP2), an important protein involved in axonal growth and the maintenance of neuronal membrane integrity, has proved to be altered in nervous system diseases. This study was aimed to investigate the role of CRMP2 in bone marrow stromal cells (BMSCs) treating rats with cerebral ischemia. BMSCs were isolated from shaft of the femurs, tibiae, and humeri and were intra-carotid administrated immediately after middle cerebral artery occlusion (MCAO). Modified Neurological Severity Scores (mNSS) was conducted at 3, 7, 14dpo and the electrophysiologic evaluation was evaluated at 14dpo. Then all rats were sacrificed and brain tissues were harvested for RT-PCR, Western blot and Immunohistochemistry analysis. We found BMSCs treatment significantly improved the neurobehavioral performance impaired by ischemic brain injury, accompanied with the notably increasing levels of Synaptophysin (SYP) and Growth associated protein 43 (GAP43). We also found the protein level of phosphorylated CRMP2 (p-CRMP2) and phosphorylation-mediated protein including Glycogen synthase kinase 3 Beta (GSK3β), Cyclin-dependent kinase 5 (CDK5) were dramatically downregulated in ischemic rats following BMSCs transplant. Furthermore, the GSK3β-mediated factors including neurotrophic and signaling factors were all significantly upregulated in BMSCs-treated group. On the basis of these findings, we suggest that the neuroplasticity effect of BMSCs on cerebral ischemia may be associated with the phosphorylated modulation of CRMP2.
authors.affiliation: Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
authors.forename: Qi-Qin
authors.initials: QQ
authors.lastname: Dan
authors.affiliation: Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Lv
authors.affiliation: Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Experimental Zoology, Kunming Medical University, Kunming, Yunnan, 650031, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.affiliation: Yunnan Key Laboratory of Stem Cells and Regenerative Medicine, Institute of Molecular and Clinical Medicine, Kunming Medical University, Kunming, Yunnan, 650031, China. Electronic address: wsf66@hotmail.com.
authors.forename: Shu-Fen
authors.initials: SF
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China; Department of Experimental Zoology, Kunming Medical University, Kunming, Yunnan, 650031, China. Electronic address: tinghua_neuron@263.net.
authors.forename: Ting-Hua
authors.initials: TH
authors.lastname: Wang
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000502:physiology*; D019054:Evoked Potentials, Motor / Q000502:physiology; D019922:GAP-43 Protein / Q000235:genetics / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000628:therapy*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D016708:Synaptophysin / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
chemical_list: D015703:Antigens, CD; D019922:GAP-43 Protein; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D016708:Synaptophysin; C095114:collapsin response mediator protein-2
keywords: Bone marrow stromal cells; Collapsin response mediator protein-2; Neuroplasticity; Phosphorylated modulation