title: Down-regulation of Nogo-A by collagen scaffolds impregnated with bone marrow stromal cell treatment after traumatic brain injury promotes axonal regeneration in rats.
abstract: Nogo-A is a major form of growth inhibitory molecule (growth-IM) which inhibits axonal regeneration and neurite regrowth after neural injury. Bone marrow stromal cells (MSCs) have been shown to inhibit Nogo-A expression in vitro and in cerebral ischemic animal models. The present study was designed to investigate the effects of treatment with human MSCs (hMSCs) impregnated into collagen scaffolds on the expression of Nogo-A and axonal plasticity after traumatic brain injury (TBI). Adult male Wistar rats were injured with controlled cortical impact and treated either with saline, hMSCs-alone or hMSCs impregnated into collagen scaffolds (scaffold+hMSC) transplanted into the lesion cavity 7 days after TBI. Rats were sacrificed 14 days after TBI and brain tissues were harvested for immunohistochemical studies, Western blot analysis, laser capture microdissections and qRT-PCR to evaluate axonal density and Nogo-A protein and gene expressions. Our data showed that treatment of TBI with scaffold+hMSC significantly decreased TBI-induced Nogo-A protein expression and increased axonal density compared to saline and hMSC-alone treatments. In addition, scaffold+hMSC transplantation decreased Nogo-A transcription in oligodendrocytes after TBI. Scaffold+hMSC treatment was superior to hMSC-alone treatment in suppressing Nogo-A expression and enhancing axonal regeneration after TBI. Our data suggest that transplanting hMSCs with scaffolds down-regulates Nogo-A transcription and protein expression which may partially contribute to the enhanced axonal regeneration after TBI.
authors.affiliation: Department of Neurosurgery, 2799W Grand Blvd, Henry Ford Hospital, Detroit, MI 48202, USA. Electronic address: amahmoo1@hfhs.org.
authors.forename: Asim
authors.initials: A
authors.lastname: Mahmood
authors.affiliation: Department of Neurosurgery, 2799W Grand Blvd, Henry Ford Hospital, Detroit, MI 48202, USA. Electronic address: hwu1@hfhs.org.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, 2799W Grand Blvd, Henry Ford Hospital, Detroit, MI 48202, USA. Electronic address: cqu1@hfhs.org.
authors.forename: Changsheng
authors.initials: C
authors.lastname: Qu
authors.affiliation: Department of Neurosurgery, 2799W Grand Blvd, Henry Ford Hospital, Detroit, MI 48202, USA. Electronic address: selina_117@hotmail.com.
authors.forename: Selina
authors.initials: S
authors.lastname: Mahmood
authors.affiliation: Department of Neurosurgery, 2799W Grand Blvd, Henry Ford Hospital, Detroit, MI 48202, USA. Electronic address: yxiong1@hfhs.org.
authors.forename: Ye
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Department of Biomedical Engineering, Science and Technology Center, Room 251, Tufts University, Boston, MA 02155, USA. Electronic address: david.kaplan@tufts.edu.
authors.forename: David
authors.initials: D
authors.lastname: Kaplan
authors.affiliation: Department of Neurology, 2799W Grand Blvd, Henry Ford Hospital, Detroit, MI 48202, USA; Department of Physics, Oakland University, 2200 North Squirrel Road, Rochester, MI 48309-4401, USA. Electronic address: mchopp1@hfhs.org.
authors.forename: Michael
authors.initials: M
authors.lastname: Chopp
mesh_terms: D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology; D016026:Bone Marrow Transplantation / Q000379:methods*; D001930:Brain Injuries / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D003094:Collagen / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000502:physiology*; D006801:Humans; D061346:Laser Capture Microdissection; D008297:Male; D009185:Myelin Proteins / Q000378:metabolism*; D009416:Nerve Regeneration / Q000502:physiology*; D000070798:Nogo Proteins; D009836:Oligodendroglia / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D054457:Tissue Scaffolds
chemical_list: D009185:Myelin Proteins; D000070798:Nogo Proteins; C000603199:RTN4 protein, human; C000603197:Rtn4 protein, rat; D003094:Collagen; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases
keywords: Axonal regeneration; Bone marrow stromal cells; CNS; ECM; Growth-IMs; LCM; MAG; MSCs; Nogo-A; OMgp; PNS; Traumatic brain injury; central nervous system; extracellular matrix; growth inhibitory molecules; laser capture microdissection; marrow stromal cells; myelin associated glycoproteins; oligodendrocytic myelin glycoprotein; peripheral nervous system