Journal of neurotrauma
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Journal of neurotrauma · Oct 2018
A Mild Traumatic Brain Injury in Mice Produces Lasting Deficits in Brain Metabolism.
Metabolic uncoupling has been well-characterized during the first minutes-to-days after a traumatic brain injury (TBI), yet mitochondrial bioenergetics during the weeks-to-months after a brain injury is poorly defined, particularly after a mild TBI. We hypothesized that a closed head injury (CHI) would be associated with deficits in mitochondrial bioenergetics at one month after the injury. A significant decrease in state-III (adenosine triphosphate production) and state-V (complex-I) driven mitochondrial respiration was found at one month post-injury in adult C57Bl/6J mice. ⋯ We also found regional variations in cerebral blood flow, including both hypo- and hyperperfusion, as measured by a pseudocontinuous arterial spin labeling MR sequence. Our results highlight a chronic deficit in mitochondrial bioenergetics associated with a CHI that may lead toward a novel approach for neurorestoration after a mild TBI. MRS provides a potential biomarker for assessing the efficacy of candidate treatments targeted at improving mitochondrial bioenergetics.
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Journal of neurotrauma · Oct 2018
Divergent induction of branched-chain aminotransferases and phosphorylation of branched chain keto-acid dehydrogenase is a potential mechanism coupling BCKA -mediated-astrocyte activation to BCAA depletion-mediated cognitive deficit after TBI.
Deficient branched-chain amino acids (BCAAs) are implicated in cognitive dysfunction after traumatic brain injury (TBI). The mechanism remains unknown. BCAAs are catabolized by neuron-specific cytosolic and astrocyte-specific mitochondrial branched-chain aminotransferases (BCATc, BCATm) to generate glutamate and branched-chain keto-acids (BCKAs) that are metabolized by the mitochondrial branched-chain keto-acid dehydrogenase (BCKD) whose activity is regulated by its phosphorylation state. ⋯ BCKD protein expression is higher in primarily cultured cortical neurons than in astrocytes, whereas pBCKD protein level is higher in astrocytes than in cortical neurons. Transforming growth factor beta treatment (10 μg/mL for 48 h) significantly increased pBCKD protein expression in astrocytes, whereas glutamate treatment (25 μM for 24 h) significantly decreased pBCKD protein in neurons. Because increased pBCKD would lead to increased BCKA accumulation, BCKA-mediated astrocyte activation, cell death, and cognitive dysfunction as found in maple syrup urine disease; thus, TBI may potentially induce cognitive deficit through diverting BCAA from glutamate production in neurons to BCKA production in astrocytes through the pBCKD-dependent mechanism.
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Journal of neurotrauma · Oct 2018
Patients with Diffuse Axonal Injury Can Recover to a Favorable Long-Term Functional and Quality of Life Outcome.
Functional outcome and quality of life are difficult to predict in patients with diffuse axonal injury (DAI) after traumatic brain injury (TBI). The primary aim of this cross-sectional cohort study was to assess the long-term functional outcome in patients with DAI and to identify prognostic factors. Second, health-related quality of life (HRQL) at long-term follow-up was assessed. ⋯ Also in patients with a DAI grade 3, a favorable outcome was seen. HRQL is a clinically relevant outcome measure because it reflects perceived outcome by patients. Independent prognostic variables for functional outcome were factors obtained in the acute phase after injury, whereas age was an independent prognostic factor for HRQL.
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Journal of neurotrauma · Oct 2018
Repeated Mild Head Injury Leads to Wide-Ranging Deficits in Higher-Order Cognitive Functions Associated with the Prefrontal Cortex.
Traumatic brain injury (TBI) has long been identified as a precipitating risk factor for higher-order cognitive deficits associated with the frontal and prefrontal cortices (PFC). In addition, mild repetitive TBI (rTBI), in particular, is being steadily recognized to increase the risk of neurodegenerative disease. Thus, further understanding of how mild rTBI changes the pathophysiology of the brain to lead to cognitive impairment is warranted. ⋯ Here, we establish that five repeated mild hits, allowing rotational acceleration of the head, lead to chronic deficits in PFC-dependent functions such as social behavior, spatial working memory, and environmental response with concomitant microgliosis and a small decrease in the adaptation rate of layer V pyramidal neurons in the medial PFC (mPFC). However, structural damage is not seen on in vivo T2-weighted magnetic resonance imaging (MRI), and extensive intrinsic excitability changes in layer V pyramidal neurons of the mPFC are not observed. Thus, this rTBI animal model can recapitulate chronic higher-order cognitive impairments without structural damage on MR imaging as observed in humans.
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Journal of neurotrauma · Oct 2018
Longitudinal Performance of Plasma Neurofilament Light and Tau in Professional Fighters: The Professional Fighters Brain Health Study.
The aim of this study is to evaluate longitudinal change in plasma neurofilament light (NF-L) and tau levels in relationship to clinical and radiological measures in professional fighters. Participants (active and retired professional fighters and control group) underwent annual blood sampling, 3-Tesla magnetic resonance imaging (MRI) brain imaging, computerized cognitive testing, and assessment of exposure to traumatic brain injury. Plasma tau and NF-L concentrations were measured using Simoa assays. ⋯ The number of sparring rounds completed by the active fighters was correlated with NF-L (95% confidence interval, 0.0116-0.4053; p = 0.0381), but not tau, levels. Among 126 subjects having multiple yearly samples, there was a significant difference in average yearly percentage change in tau across groups (F3,83 = 3.87; p = 0.0121). We conclude that plasma NF-L and tau behave differently in a group of active and retired fighters; NF-L better reflects acute exposure whereas the role of plasma tau levels in signifying chronic change in brain structure over time requires further study.