Journal of neurotrauma
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Journal of neurotrauma · Jan 2012
Identification of plasma biomarkers of TBI outcome using proteomic approaches in an APOE mouse model.
The current lack of diagnostic and prognostic biomarkers for traumatic brain injury (TBI) confounds treatment and management of patients and is of increasing concern as the TBI population grows. We have generated plasma proteomic profiles from mice receiving TBI by controlled cortical impact at either 1.3 mm or 1.8 mm depth, comparing these against those of sham injured-animals to identify plasma biomarkers specific to mild or severe TBI at 24 hours, 1 month, or 3 months post-injury. To identify possible prognostic biomarkers, we used apolipoprotein E (APOE)3 and APOE4 transgenic mice, which demonstrate relatively favorable and unfavorable outcomes respectively, following TBI. ⋯ These preliminary data clearly demonstrate plasma protein changes that are not only injury dependent but also interaction dependent. Importantly, these results demonstrate the presence of TBI-dependent and interaction-dependent plasma proteins at a 3-month time point, which is a considerable time post-injury in the mouse model, and will potentially be of significance for combat veterans receiving assessment at extended periods post-injury. Furthermore, our identification of clusters of functionally related proteins indicates disturbance of particular biological modules, which potentially increases their value beyond that of solitary biomarkers.
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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.