Affiliations: Department of Neurological Surgery, Neurotrauma
Research Center, The Miami Project to Cure Paralysis, University of Miami
Miller School of Medicine Miami, Florida, USA
Note: [] Corresponding author: W. Dalton Dietrich, Ph.D., University of
Miami Miller School of Medicine, Dept. of Neurological Surgery, 1095 NW 14th
Terrace, LPLC 2-23, Miami, FL 33136, USA. Tel.: +1 305 243 2297; Fax: +1 305
243 3207; E-mail: [email protected]
Abstract: 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.
