Journal of neurotrauma
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Journal of neurotrauma · Jan 2012
The anti-inflammatory drug carprofen improves long-term outcome and induces gliogenesis after traumatic brain injury.
Traumatic brain injury (TBI) initiates acute and chronic inflammatory processes involving cyclooxygenase-2 (COX-2), which may have detrimental effects on outcome and especially on brain regeneration. Therefore we aimed to study whether carprofen, a COX-2 inhibitor, would improve outcome and increase neurogenesis after TBI. TBI was induced in Sabra mice that were then treated with vehicle or carprofen for 7 days. ⋯ Carprofen is neuroprotective and induces cell proliferation and gliogenesis after TBI. Treatment with carprofen is consistently associated with better functional outcome. Our results imply that anti-inflammatory drugs may represent novel therapeutic options for TBI.
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Journal of neurotrauma · Jan 2012
Molecular mechanisms underlying effects of neural stem cells against traumatic axonal injury.
Transplantation of neural stem cells (NSCs) improves functional outcomes following traumatic brain injury (TBI). Previously we demonstrated that human NSCs (hNSCs) via releasing glial cell line-derived neurotrophic factor (GDNF), preserved cognitive function in rats following parasagittal fluid percussion. However, the underlying mechanisms remain elusive. ⋯ In summary, we demonstrate for the first time that hNSC grafts and treatment with GDNF acutely reduce traumatic axonal injury and promote neurite outgrowth. Possible mechanisms underlying GDNF-mediated neurite protection include balancing the activity of calcineurin, whereas GDNF-induced neurite outgrowth may result from the reduction of the abnormal α-SMA expression and actin aggregation via blocking Rho signals. Our study also suggests the necessity of further exploring the roles of α-SMA in the central nervous system (CNS), which may lead to a new avenue to facilitate recovery after TBI and other injuries.
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Journal of neurotrauma · Jan 2012
Mild hyperthermia worsens the neuropathological damage associated with mild traumatic brain injury in rats.
The effects of slight variations in brain temperature on the pathophysiological consequences of acute brain injury have been extensively described in models of moderate and severe traumatic brain injury (TBI). In contrast, limited information is available regarding the potential consequences of temperature elevations on outcome following mild TBI (mTBI) or concussions. One potential confounding variable with mTBI is the presence of elevated body temperature that occurs in the civilian or military populations due to hot environments combined with exercise or other forms of physical exertion. ⋯ In addition, pre/post-traumatic hyperthermia caused the most severe loss of NeuN-positive cells in the dentate hilus compared to normothermia. These neuropathological results demonstrate that relatively mild elevations in temperature associated with peri-traumatic events may affect the long-term functional consequences of mTBI. Because individuals exhibiting mildly elevated core temperatures may be predisposed to aggravated brain damage after mTBI or concussion, precautions should be introduced to target this important physiological variable.
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Journal of neurotrauma · Jan 2012
Ghrelin prevents disruption of the blood-brain barrier after traumatic brain injury.
Significant effort has been focused on reducing neuronal damage from post-traumatic brain injury (TBI) inflammation and blood-brain barrier (BBB)-mediated edema. The orexigenic hormone ghrelin decreases inflammation in sepsis models, and has recently been shown to be neuroprotective following subarachnoid hemorrhage. We hypothesized that ghrelin modulates cerebral vascular permeability and mediates BBB breakdown following TBI. ⋯ Our data suggest that ghrelin prevents BBB disruption after TBI. This is evident by a decrease in vascular permeability that is linked to a decrease in AQP-4. This decrease in vascular permeability may diminish post-TBI brain tissue damage was evident by decreased S100B.
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Journal of neurotrauma · Jan 2012
Mechanisms of dendritic spine remodeling in a rat model of traumatic brain injury.
Traumatic brain injury (TBI), a leading cause of death and disability in the United States, causes potentially preventable damage in part through the dysregulation of neural calcium levels. Calcium dysregulation could affect the activity of the calcium-sensitive phosphatase calcineurin (CaN), with serious implications for neural function. The present study used both an in vitro enzymatic assay and Western blot analyses to characterize the effects of lateral fluid percussion injury on CaN activity and CaN-dependent signaling in the rat forebrain. ⋯ These changes occurred bilaterally in the neocortex and hippocampus, appeared to persist for hours after injury, and coincided with synapse degeneration, as suggested by a loss of the excitatory post-synaptic protein PSD-95. Interestingly, the effect of TBI on cofilin in some brain regions was blocked by a single bolus of the CaN inhibitor FK506, given 1 h post-TBI. Overall, these findings suggest a loss of synapse stability in both hemispheres of the laterally-injured brain, and offer evidence for region-specific, CaN-dependent mechanisms.