title: Bone marrow-derived endothelial progenitor cells protect postischemic axons after traumatic brain injury.
abstract: White matter sparing after traumatic brain injury (TBI) is an important predictor of survival and outcome. Blood vessels and axons are intimately associated anatomically and developmentally. Neural input is required for appropriate vascular patterning, and vascular signaling is important for neuron development and axon growth. Owing to this codependence between endothelial cells and axons during development and the contribution of endothelial progenitor cells (EPCs) in ischemic injury, we hypothesized that EPCs are important in axonal survival after TBI. We examined the effects of allogenic-cultured EPCs on white matter protection and microvascular maintenance after midline fluid percussion injury in adult Sprague-Dawley rats. We used two in vitro models of injury, mechanical stretch and oxygen-glucose deprivation (OGD), to examine the effects of EPCs on the mechanical and ischemic components of brain trauma, respectively. Our results indicate that EPCs improve the white matter integrity and decrease capillary breakdown after injury. Cultured cortical neurons exposed to OGD had less axon degeneration when treated with EPC-conditioned media, whereas no effect was seen in axons injured by mechanical stretch. The results indicate that EPCs are important for the protection of the white matter after trauma and represent a potential avenue for therapy.
authors.affiliation: Keenan Research Centre in the Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, Ontario, Canada.
authors.forename: Katya J
authors.initials: KJ
authors.lastname: Park
authors.affiliation: Keenan Research Centre in the Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, Ontario, Canada.
authors.forename: Eugene
authors.initials: E
authors.lastname: Park
authors.affiliation: Keenan Research Centre in the Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, Ontario, Canada.
authors.forename: Elaine
authors.initials: E
authors.lastname: Liu
authors.affiliation: 1] Keenan Research Centre in the Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, Ontario, Canada [2] Departments of Critical Care and Anesthesia, St Michael's Hospital, Toronto, Ontario, Canada [3] Department of Anesthesia and Interdepartmental Division of Critical Care, University of Toronto, Toronto, Ontario Canada.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Baker
mesh_terms: D064591:Allografts; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology; D001854:Bone Marrow Cells / Q000378:metabolism*; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism / Q000637:transplantation; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism*