Widespread cellular proliferation and focal neurogenesis after traumatic brain injury in the rat

Abstract. Purpose: A proliferation of stem/progenitor cells is observed after brain injury. We examined the regional andtemporal profile of mitotically active cells to determine whether traumatic brain injury (TBI) would increase neurogenesis inselective brain regions.Methods: MaleSprague-Dawley ratsreceived injections(IP)of5-bromo-deoxyuridine (BrdU),acompound used todetectmitoticcells, before and after fluid-percussion brain injury. At 3 hr, 1, 2, 3, 7, and 14 days after moderate fluid percussion, brainswere 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 traumatizedhemisphere. At later time points, a significant increase in BrdU positive cells was observed throughout the traumatized cerebralcortex, hippocampus, white matter structures, and some contralateral regions. BrdU labeled cells were observed as late as14 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 focalneurogenesis in the dentate gyrus of the hippocampus. These cellular responses to injury may participate in brain repair andfunctional recovery.Keywords: Neurogenesis, dentate granular neurons, trauma, subventricular zone, plasticity