Journal of neurotrauma
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Journal of neurotrauma · Oct 2018
Neuroinflammation after Traumatic Brain Injury Is Enhanced in Activating Transcription Factor 3 Mutant Mice.
Traumatic brain injury (TBI) induces a neuroinflammatory response resulting in astrocyte and microglia activation at the lesion site. This involves upregulation of neuroinflammatory genes, including chemokines and interleukins. However, so far, there is lack of knowledge on transcription factors (TFs) modulating this TBI-associated gene expression response. ⋯ In Atf3 mutant mice, mRNA abundance was further enhanced upon TBI compared to wild-type mice, suggesting immune gene repression by wild-type ATF3. In accord, more immune cells were present in the lesion area of ATF3-deficient mice. Overall, we identified ATF3 as a new TF-mediating TBI-associated CNS inflammatory responses.
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Journal of neurotrauma · Oct 2018
Polarization of Microglia to the M2 Phenotype in a Peroxisome Proliferator-Activated Receptor Gamma-Dependent Manner Attenuates Axonal Injury Induced by Traumatic Brain Injury in Mice.
Increasing evidence indicates that activated microglia play an important role in the inflammatory response following traumatic brain injury (TBI). Inhibiting M1 and stimulating M2 activated microglia have demonstrated protective effects in several animal models of central nervous system diseases. However, it is not clear whether the polarization of microglia to M2 attenuates axonal injury following TBI. ⋯ Conversely, GW9662 inhibited the polarization of microglia to M2 and aggravated inflammation and axonal injury. Our in vitro findings in lipopolysaccharide-induced microglia were consistent with those of our in vivo experiments. In conclusion, the polarization of microglia to the M2 phenotype via PPAR-γ activation attenuated axonal injury following TBI in mice, which may be a potential therapeutic approach for TBI-induced axonal injury.
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Journal of neurotrauma · Sep 2018
Investigation of Microbiota Alterations and Intestinal Inflammation Post-Spinal Cord Injury in Rat Model.
Although there has been a significant amount of research focused on the pathophysiology of spinal cord injury (SCI), there is limited information on the consequences of SCI on remote organs. SCI can produce significant effects on a variety of organ systems, including the gastrointestinal tract. Patients with SCI often suffer from severe, debilitating bowel dysfunction in addition to their physical disabilities, which is of major concern for these individuals because of the adverse impact on their quality of life. ⋯ Proinflammatory cytokines interleukin (IL)-12, macrophage inflammatory protein-2 (MIP-2), and tumor necrosis factor alpha were found to be significantly elevated in intestinal tissue homogenate 4 weeks post-SCI compared to 8-weeks post-injury. Further, levels of IL-1β, IL-12, and MIP-2 significantly correlated with changes in beta diversity 8-weeks post-SCI. Our data provide a greater understanding of the early effects of SCI on the microbiota and gastrointestinal tract, highlighting the need for further investigation to elucidate the mechanism underlying these effects.
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Journal of neurotrauma · Sep 2018
Unique Sensory and Motor Behavior in Thy1-GFP-M Mice before and after Spinal Cord Injury.
Sensorimotor recovery after spinal cord injury (SCI) is of utmost importance to injured individuals and will rely on improved understanding of SCI pathology and recovery. Novel transgenic mouse lines facilitate discovery, but must be understood to be effective. The purpose of this study was to characterize the sensory and motor behavior of a common transgenic mouse line (Thy1-GFP-M) before and after SCI. ⋯ Importantly, consistent findings across TG+ and TG- groups suggest that the effects are mediated by the genetic background rather than transgene manipulation itself. Surprisingly, TM training restored mechanical and thermal sensation to baseline levels in TG+ mice with SCI. This behavioral profile and responsiveness to chronic training will be important to consider when choosing models to study the mechanisms underlying sensorimotor recovery after SCI.
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Journal of neurotrauma · Sep 2018
Editorial CommentStimulating the Injured Spinal Cord: Plenty to Grasp.