Articles: traumatic-brain-injuries.
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To study the effect of simvastatin on neurological functional recovery after traumatic brain injuries (TBI) and the possible molecular mechanisms, we evaluated simvastatin-induced proliferation and differentiation of neural stem cells (NSCs) in vitro and in vivo and possible involvement of Notch-1 signaling in this process. ⋯ Simvastatin treatment enhanced neurological functional recovery after TBI possibly via activation of Notch signaling and increasing neurogenesis in the injured area.
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Proc. Natl. Acad. Sci. U.S.A. · Mar 2015
HDAC inhibition prevents white matter injury by modulating microglia/macrophage polarization through the GSK3β/PTEN/Akt axis.
Severe traumatic brain injury (TBI) elicits destruction of both gray and white matter, which is exacerbated by secondary proinflammatory responses. Although white matter injury (WMI) is strongly correlated with poor neurological status, the maintenance of white matter integrity is poorly understood, and no current therapies protect both gray and white matter. One candidate approach that may fulfill this role is inhibition of class I/II histone deacetylases (HDACs). ⋯ These findings are consistent with recent findings that microglial phenotypic switching modulates white matter repair and axonal remyelination and highlight a previously unexplored role for HDAC activity in this process. Furthermore, the functions of GSK3β may be more subtle than previously thought, in that GSK3β can modulate microglial functions via the PTEN/PI3K/Akt signaling pathway and preserve white matter homeostasis. Thus, inhibition of HDACs in microglia is a potential future therapy in TBI and other neurological conditions with white matter destruction.
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Human brain mapping · Mar 2015
Close-range blast exposure is associated with altered functional connectivity in Veterans independent of concussion symptoms at time of exposure.
Although there is emerging data on the effects of blast-related concussion (or mTBI) on cognition, the effects of blast exposure itself on the brain have only recently been explored. Toward this end, we examine functional connectivity to the posterior cingulate cortex, a primary region within the default mode network (DMN), in a cohort of 134 Iraq and Afghanistan Veterans characterized for a range of common military-associated comorbidities. Exposure to a blast at close range (<10 meters) was associated with decreased connectivity of bilateral primary somatosensory and motor cortices, and these changes were not different from those seen in participants with blast-related mTBI. ⋯ In contrast, differences in functional connectivity based on concussion history and blast exposures at greater distances were not apparent. Despite the limitations of a study of this nature (e.g., assessments long removed from injury, self-reported blast history), these data demonstrate that blast exposure per se, which is prevalent among those who served in Iraq and Afghanistan, may be an important consideration in Veterans' health. It further offers a clinical guideline for determining which blasts (namely, those within 10 meters) are likely to lead to long-term health concerns and may be more accurate than using concussion symptoms alone.
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Journal of neurosurgery · Mar 2015
Review Meta AnalysisImpact of intracranial pressure monitoring on mortality in patients with traumatic brain injury: a systematic review and meta-analysis.
Some studies have demonstrated that intracranial pressure (ICP) monitoring reduces the mortality of traumatic brain injury (TBI). But other studies have shown that ICP monitoring is associated with increased mortality. Thus, the authors performed a meta-analysis of studies comparing ICP monitoring with no ICP monitoring in patients who have suffered a TBI to determine if differences exist between these strategies with respect to mortality, intensive care unit (ICU) length of stay (LOS), and hospital LOS. ⋯ In this systematic review and meta-analysis of ICP monitoring studies, the authors found that the current clinical evidence does not indicate that ICP monitoring overall is significantly superior to no ICP monitoring in terms of the mortality of TBI patients. However, studies published after 2012 indicated a lower mortality in patients who underwent ICP monitoring.
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Brain Behav. Immun. · Mar 2015
Randomized Controlled Trial Observational StudyVariable neuroendocrine-immune dysfunction in individuals with unfavorable outcome after severe traumatic brain injury.
Bidirectional communication between the immune and neuroendocrine systems is not well understood in the context of traumatic brain injury (TBI). The purpose of this study was to characterize relationships between cerebrospinal fluid (CSF) cortisol and inflammation after TBI, and to determine how these relationships differ by outcome. CSF samples were collected from 91 subjects with severe TBI during days 0-6 post-injury, analyzed for cortisol and inflammatory markers, and compared to healthy controls (n=13 cortisol, n=11 inflammatory markers). ⋯ Our results suggest that unfavorable outcome after TBI may result from dysfunctional neuroendocrine-immune communication wherein an adequate immune response is not mounted or, alternatively, neuroinflammation is prolonged. Importantly, the nature of neuroendocrine-immune dysfunction differs between cortisol TRAJ groups. These results present a novel biomarker-based index from which to discriminate outcome and emphasize the need for evaluating tailored treatments targeting inflammation early after injury.