TY - JOUR
T1 - Widespread cellular proliferation and focal neurogenesis after traumatic brain injury in the rat
AU - Urrea, Carlos
AU - Castellanos, Daniel A.
AU - Sagen, Jacqueline
AU - Tsoulfas, Pantelis
AU - Bramlett, Helen M.
AU - Dietrich, W. Dalton
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2007
Y1 - 2007
N2 - Purpose: A proliferation of stem/progenitor cells is observed after brain injury. We examined the regional and temporal profile of mitotically active cells to determine whether traumatic brain injury (TBI) would increase neurogenesis in selective brain regions. Methods: Male Sprague-Dawley rats received injections (IP) of 5-bromo-deoxyuridine (BrdU), a compound used to detect mitotic cells, before and after fluid-percussion brain injury. At 3 hr, 1, 2, 3, 7, and 14 days after moderate fluid percussion, brains were processed for immunocytochemical and confocal analysis. Sections were double-labeled for markers selective for neurons (NeuN), astrocytes (GFAP), olidgodendrocytes (CNPase and MBP) and macrophage/microglia (ED1). Results: At 3 hr post-trauma, the majority of BrdU labeled cells were associated with the subventricular zone of the traumatized hemisphere. At later time points, a significant increase in BrdU positive cells was observed throughout the traumatized cerebral cortex, hippocampus, white matter structures, and some contralateral regions. BrdU labeled cells were observed as late as 14 days post-injury. Double-label studies with confocal microscopy demonstrated that cell phenotypes including astrocytes, macrophage/microglia, oligodendrocytes, and neurons were BrdU positive with the majority of cells appearing glial in nature. Evidence for neurogenesis was seen in the granular cell layer of the hippocampus. Conclusion: These findings indicate that TBI stimulates widespread cellular proliferation for days after injury and results in focal neurogenesis in the dentate gyrus of the hippocampus. These cellular responses to injury may participate in brain repair and functional recovery.
AB - Purpose: A proliferation of stem/progenitor cells is observed after brain injury. We examined the regional and temporal profile of mitotically active cells to determine whether traumatic brain injury (TBI) would increase neurogenesis in selective brain regions. Methods: Male Sprague-Dawley rats received injections (IP) of 5-bromo-deoxyuridine (BrdU), a compound used to detect mitotic cells, before and after fluid-percussion brain injury. At 3 hr, 1, 2, 3, 7, and 14 days after moderate fluid percussion, brains were processed for immunocytochemical and confocal analysis. Sections were double-labeled for markers selective for neurons (NeuN), astrocytes (GFAP), olidgodendrocytes (CNPase and MBP) and macrophage/microglia (ED1). Results: At 3 hr post-trauma, the majority of BrdU labeled cells were associated with the subventricular zone of the traumatized hemisphere. At later time points, a significant increase in BrdU positive cells was observed throughout the traumatized cerebral cortex, hippocampus, white matter structures, and some contralateral regions. BrdU labeled cells were observed as late as 14 days post-injury. Double-label studies with confocal microscopy demonstrated that cell phenotypes including astrocytes, macrophage/microglia, oligodendrocytes, and neurons were BrdU positive with the majority of cells appearing glial in nature. Evidence for neurogenesis was seen in the granular cell layer of the hippocampus. Conclusion: These findings indicate that TBI stimulates widespread cellular proliferation for days after injury and results in focal neurogenesis in the dentate gyrus of the hippocampus. These cellular responses to injury may participate in brain repair and functional recovery.
KW - Dentate granular neurons
KW - Neurogenesis
KW - Plasticity
KW - Subventricular zone
KW - Trauma
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M3 - Article
C2 - 17473396
AN - SCOPUS:34247344526
VL - 25
SP - 65
EP - 76
JO - Restorative Neurology and Neuroscience
JF - Restorative Neurology and Neuroscience
SN - 0922-6028
IS - 1
ER -