title: Endogenous neural stem/progenitor cells stabilize the cortical microenvironment after traumatic brain injury.
abstract: Although a myriad of pathological responses contribute to traumatic brain injury (TBI), cerebral dysfunction has been closely linked to cell death mechanisms. A number of therapeutic strategies have been studied in an attempt to minimize or ameliorate tissue damage; however, few studies have evaluated the inherent protective capacity of the brain. Endogenous neural stem/progenitor cells (NSPCs) reside in distinct brain regions and have been shown to respond to tissue damage by migrating to regions of injury. Until now, it remained unknown whether these cells have the capacity to promote endogenous repair. We ablated NSPCs in the subventricular zone to examine their contribution to the injury microenvironment after controlled cortical impact (CCI) injury. Studies were performed in transgenic mice expressing the herpes simplex virus thymidine kinase gene under the control of the nestin(δ) promoter exposed to CCI injury. Two weeks after CCI injury, mice deficient in NSPCs had reduced neuronal survival in the perilesional cortex and fewer Iba-1-positive and glial fibrillary acidic protein-positive glial cells but increased glial hypertrophy at the injury site. These findings suggest that the presence of NSPCs play a supportive role in the cortex to promote neuronal survival and glial cell expansion after TBI injury, which corresponds with improvements in motor function. We conclude that enhancing this endogenous response may have acute protective roles after TBI.
authors.affiliation: 1The Miami Project to Cure Paralysis and Department of Neurological Surgery, University of Miami, Miami, Florida.
authors.forename: Kirsty J
authors.initials: KJ
authors.lastname: Dixon
authors.affiliation: 2The Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Blacksburg, Virginia.
authors.forename: Michelle H
authors.initials: MH
authors.lastname: Theus
authors.affiliation: 1The Miami Project to Cure Paralysis and Department of Neurological Surgery, University of Miami, Miami, Florida.
authors.forename: Claudiu M
authors.initials: CM
authors.lastname: Nelersa
authors.affiliation: 1The Miami Project to Cure Paralysis and Department of Neurological Surgery, University of Miami, Miami, Florida.
authors.forename: Jose
authors.initials: J
authors.lastname: Mier
authors.affiliation: 1The Miami Project to Cure Paralysis and Department of Neurological Surgery, University of Miami, Miami, Florida.
authors.forename: Lissette G
authors.initials: LG
authors.lastname: Travieso
authors.affiliation: 3Department of Pathology and Cell Biology, Columbia University, New York, New York.
authors.forename: Tzong-Shiue
authors.initials: TS
authors.lastname: Yu
authors.affiliation: 3Department of Pathology and Cell Biology, Columbia University, New York, New York.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Kernie
authors.affiliation: 1The Miami Project to Cure Paralysis and Department of Neurological Surgery, University of Miami, Miami, Florida.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Liebl
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D060833:Cellular Microenvironment / Q000502:physiology*; D002540:Cerebral Cortex / Q000166:cytology* / Q000378:metabolism*; D020547:Lateral Ventricles / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D058953:Neural Stem Cells / Q000378:metabolism* / Q000473:pathology; D055495:Neurogenesis / Q000502:physiology
keywords: gliosis; neural stem/progenitor cell ablation; neurogenesis; neuronal survival; traumatic brain injury