Journal of neurotrauma
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Journal of neurotrauma · Mar 2011
Preclinical efficacy testing in middle-aged rats: nicotinamide, a novel neuroprotectant, demonstrates diminished preclinical efficacy after controlled cortical impact.
Age is a consistent predictor of poor outcome following traumatic brain injury (TBI). Although the elderly population has one of the highest rates of TBI-related hospitalization and death, few preclinical studies have attempted to model and treat TBI in the aged population. Recent studies have indicated that nicotinamide (NAM), a soluble B-group vitamin, improved functional recovery in experimental models of TBI in young animals. ⋯ In summary, the preclinical efficacy of NAM as a treatment following CCI in middle-aged rats differs from that previously documented in younger rats; while treatment with 50 mg/kg NAM appeared to have no effect, the 500-mg/kg dose worsened performance in middle-aged animals. Histological indicators demonstrated more nuanced group differences, indicating that NAM may positively impact some of the cellular cascades following injury, but were not substantial enough to improve functional recovery. These findings emphasize the need to examine potential treatments for TBI utilizing non-standard populations, and may explain why so many treatments have failed in clinical trials.
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Journal of neurotrauma · Mar 2011
Incidence of traumatic spinal cord injury in Aragón, Spain (1972-2008).
Long-term incidence studies are required to identify high-risk groups, establish trends, and forecast needs, and thus contribute to health care planning in spinal cord injury (SCI). This study aimed to determine the incidence of traumatic SCI over a 36-year period in Aragón, Spain, and compare rates with other published European estimates. Hospital records from the Servet Hospital, the only specialized SCI unit in the region, of a retrospective cohort with traumatic SCI between January 1972 and December 2008 were reviewed. ⋯ The proportion of SCI cases in persons older than 60 years, mostly due to falls, is increasing. The age-adjusted incidence rates found for the region of Aragón in Spain fall within the range of other published European estimates. Comparative epidemiological features for 2001-2008 suggest that there is room for prevention.
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Journal of neurotrauma · Mar 2011
Aquaporin-4 expression in cultured astrocytes after fluid percussion injury.
The development of cytotoxic brain edema resulting in increased intracranial pressure is a major cause of death occurring in the early phase of traumatic brain injury (TBI). Such edema predominantly develops as a consequence of astrocyte swelling. We recently documented that fluid percussion injury (FPI) to cultured astrocytes causes cell swelling. ⋯ We now show that inhibition of these factors reduces the upregulation of AQP4 following trauma. Since TBI has been shown to activate nuclear factor-kappa B (NF-κB), as well as the Na(+),K(+),Cl(-) co-transporter (NKCC), both of which are implicated in brain edema/astrocyte swelling in other conditions, we also examined the effect of BAY 11-7082 and bumetanide, inhibitors of NF-κB and NKCC, respectively, and found that these agents also significantly inhibited the trauma-induced AQP4 upregulation. Our findings show that in vitro trauma upregulates AQP4, and that ONS, MAPKs, mPT, NF-κB, and NKCC are involved in its upregulation.
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Journal of neurotrauma · Mar 2011
Stereology and ultrastructure of chronic phase axonal and cell soma pathology in stretch-injured central nerve fibers.
Magnetic resonance imaging (MRI) suggests that with survival after human traumatic brain injury (TBI), there is ongoing loss of white and grey matter from the injured brain during the chronic phase. However; direct quantitative experimental evidence in support of this observation is lacking. Using the guinea pig stretch-injury optic nerve model, quantitative evidence by stereology of damage to the optic nerve and retina was sought. ⋯ There was hypertrophy and proliferation of glial cells within the surrounding neuropil. A relatively low-grade loss of retinal ganglion cells occurred throughout the experiment, with about 60% remaining at 12 weeks' survival. We provide quantitative evidence that after traumatic axonal injury (TAI) there is a continuing loss of nerve fibers and their cell bodies from a CNS tract over a 3-month post-traumatic interval.
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Journal of neurotrauma · Mar 2011
A model of low-level primary blast brain trauma results in cytoskeletal proteolysis and chronic functional impairment in the absence of lung barotrauma.
Shock-wave exposure from improvised explosive devices (IEDs) has been implicated as a possible contributing factor to neurological impairment reported in combat veterans. However, evidence-based substantiation of this implication, particularly for low-level exposure in the absence of external signs of trauma, remain elusive. Accordingly, we constructed an open-ended shock tube producing a short-duration, low-amplitude shockwave. ⋯ Evoked compound action potential (CAP) recordings from the corpus callosum showed a significant increase in the duration of CAP responses at 14 and 30 days post-injury, and a gradual depression in the unmyelinated fiber amplitude. Shielding the head attenuated αII-spectrin cytoskeletal breakdown, thus directly implicating low-level shock-wave exposure as a cause of brain injury in the rat. Despite anatomical and scaling differences in rats compared to humans, the results suggest the potential for undiagnosed traumatic brain pathologies occurring in combat veterans following shock-wave exposure.