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
Hypersensitive glutamate signaling correlates with the development of late-onset behavioral morbidity in diffuse brain-injured circuitry.
In diffuse brain-injured rats, robust sensory sensitivity to manual whisker stimulation develops over 1 month post-injury, comparable to agitation expressed by brain-injured individuals with overstimulation. In the rat, whisker somatosensation relies on thalamocortical glutamatergic relays between the ventral posterior medial (VPM) thalamus and barrel fields of somatosensory cortex (S1BF). Using novel glutamate-selective microelectrode arrays coupled to amperometry, we test the hypothesis that disrupted glutamatergic neurotransmission underlies the whisker sensory sensitivity associated with diffuse brain injury. ⋯ In conjunction with no changes in glutamate transporter gene expression and exogenous glutamate clearance efficiency, these data support a presynaptic origin for enduring post-traumatic circuit alterations. In the anatomically-distinct whisker circuit, the injury-induced functional alterations correlate with the development of late-onset behavioral morbidity. Effective therapies to modulate presynaptic glutamate function in diffuse-injured circuits may translate into improvements in essential brain function and behavioral performance in other brain-injured circuits in rodents and in humans.
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Journal of neurotrauma · Jan 2012
Blast-induced tinnitus and hearing loss in rats: behavioral and imaging assays.
Abstract The current study used a rat model to investigate the underlying mechanisms of blast-induced tinnitus, hearing loss, and associated traumatic brain injury (TBI). Seven rats were used to evaluate behavioral evidence of tinnitus and hearing loss, and TBI using magnetic resonance imaging following a single 10-msec blast at 14 psi or 194 dB sound pressure level (SPL). The results demonstrated that the blast exposure induced early onset of tinnitus and central hearing impairment at a broad frequency range. ⋯ No significant microstructural changes found in the corpus callosum indicates that the currently adopted blast exposure mainly exerts effects through the auditory pathways rather than through direct impact onto the brain parenchyma. The results showed that this animal model is appropriate for investigation of the mechanisms underlying blast-induced tinnitus, hearing loss, and related TBI. Continued investigation along these lines will help identify pathology with injury/recovery patterns, aiding development of effective treatment strategies.
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Journal of neurotrauma · Jan 2012
Low-level laser light therapy improves cognitive deficits and inhibits microglial activation after controlled cortical impact in mice.
Low-level laser light therapy (LLLT) exerts beneficial effects on motor and histopathological outcomes after experimental traumatic brain injury (TBI), and coherent near-infrared light has been reported to improve cognitive function in patients with chronic TBI. However, the effects of LLLT on cognitive recovery in experimental TBI are unknown. We hypothesized that LLLT administered after controlled cortical impact (CCI) would improve post-injury Morris water maze (MWM) performance. ⋯ Little or no effect of LLLT on post-injury cognitive function was observed using the other doses, a 4-h administration time point and 7-day administration of 60 J/cm². No effect of LLLT (60 J/cm² open craniotomy) was observed on post-injury motor function (days 1-7), brain edema (24 h), nitrosative stress (24 h), or lesion volume (14 days). Although further dose optimization and mechanism studies are needed, the data suggest that LLLT might be a therapeutic option to improve cognitive recovery and limit inflammation after TBI.
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Journal of neurotrauma · Jan 2012
In vivo bioluminescent imaging of a new model of infectious complications in head-injury rats.
Infectious complications are responsible for 10-25% of mortality in head-injured patients. In the present work we developed a model of infectious complications in head-injury rats using Escherichia coli (E. coli) with a stable copy of the lux operon, and monitored the infection in vivo by optical imaging. Rats were randomized into three groups: AL (healthy rats), HI (head-injury rats), and HI-EC (HI rats+single enteral bolus of E. coli, 1.3×10(9)/rat given 2 days after HI). ⋯ Bacterial challenge was associated with a specific body weight loss and a decrease in gastrocnemius protein content, in alanine (AL 512±41 versus HI-EC 395±29 μmol/L; p<0.05), and in sulfur plasma amino acids. In conclusion, we propose a controlled model of HI with infectious complications characterized by specific metabolic alterations. Combined with the in vivo monitoring of the infection by bioluminescence, this model offers a valuable tool to evaluate specific strategies for HI patients.