Journal of neurotrauma
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Journal of neurotrauma · Sep 2015
A combination therapy of 17β-estradiol and memantine is more neuroprotective than monotherapies in an organotypic brain slice culture model of traumatic brain injury.
Combination therapies are a promising therapeutic option for traumatic brain injury (TBI) owing to the clinical failure of monotherapy treatments, such as progesterone. Organotypic hippocampal slice cultures (OHSCs) from Sprague-Dawley rats were subjected to an in vitro TBI, and the neuroprotective effects of 17β-estradiol (E2) or memantine (MEM) monotherapies were quantified. Several combination treatments at different concentrations of both drugs were tested, with 100 pM of E2 and 10 μM of MEM statistically and significantly reducing cell death over either monotherapy when administered immediately after injury. ⋯ Further, we hypothesized that this synergy could be the result of MEM blocking a potentially deleterious effect of E2, specifically E2 enhancement of N-methyl-D-aspartate (NMDA) currents. Evoked electrophysiological responses in OHSCs were potentiated by E2 treatment, whereas this potentiation was significantly reduced by MEM. In conclusion, a combination therapy of E2 and memantine was significantly more neuroprotective than both monotherapy treatments, and this synergy may be the result of MEM blocking a deleterious E2-mediated enhancement of NMDA receptors.
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Journal of neurotrauma · Aug 2015
Comparative StudyNo Significant Acute and Subacute Differences between Blast and Blunt Concussions across Multiple Neurocognitive Measures and Symptoms in Deployed Soldiers.
Seventy-one deployed U. S. Army soldiers who presented for concussion care due to either blast or blunt mechanisms within 72 h of injury were assessed using the Military Acute Concussion Evaluation, the Automated Neuropsychological Assessment Metrics (ANAM), traditional neuropsychological tests, and health status questionnaires. ⋯ Pre-injury baseline ANAM scores were compared where available, and revealed no statistically significant differences between 22 blast injury and eight blunt injury participants. These findings suggest there are no significant differences between mechanisms of injury during both the acute and subacute periods in neurobehavioral concussion sequelae while deployed in a combat environment. The current study supports the use of sports/mechanical concussion models for early concussion management in the deployed setting and exploration of variability in potential long-term outcomes.
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Journal of neurotrauma · Aug 2015
Randomized Controlled Trial Multicenter StudyAmantadine Effect on Perceptions of Irritability after Traumatic Brain Injury: Results of the Amantadine Irritability Multisite Study (AIMS).
This study examines the effect of amantadine on irritability in persons in the post-acute period after traumatic brain injury (TBI). There were 168 persons ≥6 months post-TBI with irritability who were enrolled in a parallel-group, randomized, double-blind, placebo-controlled trial receiving either amantadine 100 mg twice daily or equivalent placebo for 60 days. Subjects were assessed at baseline and days 28 (primary end-point) and 60 of treatment using observer-rated and participant-rated Neuropsychiatric Inventory (NPI-I) Most Problematic item (primary outcome), NPI Most Aberrant item, and NPI-I Distress Scores, as well as physician-rated Clinical Global Impressions (CGI) scale. ⋯ While observers in both groups reported large improvements, significant group differences were not found for the primary outcome (observer ratings) at either day 28 or 60. This large placebo or nonspecific effect may have masked detection of a treatment effect. The result of this study of amantadine 100 mg every morning and noon to reduce irritability was not positive from the observer perspective, although there are indications of improvement at day 60 from the perspective of persons with TBI and clinicians that may warrant further investigation.
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Journal of neurotrauma · Aug 2015
Multicenter StudyAbnormal white matter BOLD signals in chronic mild traumatic brain injury.
Concussion, or mild traumatic brain injury (mTBI), can cause persistent behavioral symptoms and cognitive impairment, but it is unclear if this condition is associated with detectable structural or functional brain changes. At two sites, chronic mTBI human subjects with persistent post-concussive symptoms (three months to five years after injury) and age- and education-matched healthy human control subjects underwent extensive neuropsychological and visual tracking eye movement tests. At one site, patients and controls also performed the visual tracking tasks while blood-oxygen-level-dependent (BOLD) signals were measured with functional magnetic resonance imaging. ⋯ In contrast, BOLD signals were normal in cortical regions, such as the frontal eye field and intraparietal sulcus, that mediate oculomotor and attention functions necessary for visual tracking. The abnormal BOLD signals accurately differentiated chronic mTBI patients from healthy controls at the single-subject level, although they did not correlate with symptoms or neuropsychological performance. We conclude that subjects with persistent post-concussive symptoms can be identified years after their TBI using fMRI and an eye movement task despite showing normal structural MRI and DTI.
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Journal of neurotrauma · Aug 2015
Mortality following traumatic brain injury inpatient rehabilitation.
The aim of this study was to examine the rate and causes of mortality following mild to severe traumatic brain injury (TBI) rehabilitation and to develop a multivariate prognostic model of mortality. We conducted a cohort study of 3341 individuals with mild to severe TBI followed-up from a post-acute inpatient rehabilitation center. Rate of death and survival between one and 26 years following injury were examined using standardized mortality ratios (SMRs) and prognostic models developed using Cox regression. ⋯ Premorbid lifestyle factors exerted a greater influence on mortality following TBI, compared with injury-related factors. This risk was especially prominent for younger individuals, who died primarily due to external causes. These findings highlight the need for interventions that address premorbid issues, such as substance abuse and mental health issues.