Abstract
Spinal cord injury (SCI) triggers a complex cellular response at the injury site, leading to the formation of a dense scar tissue. Despite this local tissue remodeling, the consequences of SCI at the cellular level in distant rostral sites (i.e., brain), remain unknown. In this study, we asked whether cervical SCI could alter cell dynamics in neurogenic areas of the adult rat forebrain. To this aim, we quantified BrdU incorporation and determined the phenotypes of newly generated cells (neurons, astrocytes, or microglia) during the subchronic and chronic phases of injury. We find that subchronic SCI leads to a reduction of BrdU incorporation and neurogenesis in the olfactory bulb and in the hippocampal dentate gyrus. By contrast, subchronic SCI triggers an increased BrdU incorporation in the dorsal vagal complex of the hindbrain, where most of the newly generated cells are identified as microglia. In chronic condition 90 days after SCI, BrdU incorporation returns to control levels in all regions examined, except in the hippocampus, where SCI produces a long-term reduction of neurogenesis, indicating that this structure is particularly sensitive to SCI. Finally, we observe that SCI triggers an acute inflammatory response in all brain regions examined, as well as a hippocampal-specific decline in BDNF levels. This study provides the first demonstration that forebrain neurogenesis is vulnerable to a distal SCI.
Highlights
Central nervous insults, such as spinal cord injury (SCI) or traumatic brain injury (TBI), are among the leading causes of mortality and morbidity worldwide
The effects of SCI were investigated in three supra-spinal brain areas where ongoing adult neurogenesis has been described: the subventricular zone (SVZ)/olfactory bulb (OB) system (Doetsch and Alvarez-Buylla, 1996), the subgranular zone (SGZ) (Altman and Das, 1965), and the dorsal vagal complex (DVC) (Bauer et al, 2005)
To address the possibility that SCI-induced modulation of neurogenesis could vary as a function of time after the lesion, we studied two time points, a subchronic condition 15 dpi and a chronic condition 90 dpi
Summary
Central nervous insults, such as spinal cord injury (SCI) or traumatic brain injury (TBI), are among the leading causes of mortality and morbidity worldwide. The underlying cellular mechanisms remain unclear, but may comprise dendritic remodeling, axonal sprouting, as well as local neuronal circuit reorganization (Darian-Smith, 2009). Another feature that could contribute to this post-injury neuroplasticity is injury-induced neurogenesis (Kazanis, 2009). Following TBI, cell proliferation and neurogenesis increase in the hippocampal dentate gyrus (Kernie et al, 2001; Rola et al, 2006; Sun et al, 2007; Urrea et al, 2007; Yu et al, 2008), and a recent study using a mouse model of TBI showed that newly generated neurons in this region persist over time and might participate in the cognitive recovery (Blaiss et al, 2011)
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