Journal of neurotrauma
-
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.
-
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.
-
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.
-
Journal of neurotrauma · Oct 2018
Dietary Zinc Modulates Matrix Metalloproteinases in Traumatic Brain Injury.
Animal models of mild traumatic brain injury (mTBI) provide opportunity to examine the extent to which dietary interventions can be used to improve recovery after injury. Animal studies also suggest that matrix metalloproteinases (MMPs) play a role in tissue remodeling post-TBI. Because dietary zinc (Zn) improved recovery in nonblast mTBI models, and the MMPs are Zn-requiring enzymes, we evaluated the effects of low- (LoZn) and adequate-Zn (AdZn) diets on MMP expression and behavioral responses, subsequent to exposure to a single blast. ⋯ Because the blast injuries occurred while animals were under general anesthesia, the increased immobility observed post-injury in rats consuming LoZn diets suggest that blast mTBI can, in the absence of any psychological stressor, induce post-traumatic stress disorder-related traits that are chronic, but responsive to diet. Taken together, our results support a relationship between marginally Zn-deficient status and a compromised regenerative response post-injury in muscle, likely through the MMP pathway. However, in neuronal tissue, changes in MMP/TIMP levels after blast indicate a variable response to marginally Zn-deficient diets that may help explain compromised repair mechanism(s) previously associated with the systemic hypozincemia that develops in patients with TBI.
-
Journal of neurotrauma · Oct 2018
MicroRNA-711-Induced Downregulation of Angiopoietin-1 Mediates Neuronal Cell Death.
Angiopoietin-1 (Ang-1) is a well-known endothelial growth factor, but its effects on neurons have yet to be elucidated. We show that Ang-1 is rapidly downregulated in the injured brain after controlled cortical impact (CCI), a mouse experimental traumatic brain injury (TBI) model and in etoposide-induced neuronal apoptosis in vitro. Ang-1 treatment inhibits etoposide-induced upregulation of proapoptotic B-cell lymphoma 2 (Bcl-2) family members Noxa, p53 upregulated modulator of apoptosis (Puma), Bcl-2 interacting mediator of cell death (Bim), and Bcl-2-associated X protein (Bax); reduces markers of caspase-dependent (cytochrome c release/caspase activation) and caspase-independent (apoptosis-inducing factor release) pathways; and limits neuronal cell death. ⋯ Administration of miR-711 inhibitor elevates Ang-1 after TBI whereas Ang-1 administration increases Akt activation; reduces Puma, Noxa, Bim, and Bax levels; and attenuates caspase-dependent and -independent neuronal apoptosis 24 h after TBI. Ang-1 also attenuates neuronal degeneration, increases gene expression of molecules that maintain blood-brain barrier integrity, and reduces post-traumatic lesion volume/edema 24 h after TBI. Although we only observed short-term neuroprotective effects after Ang-1 administration, miR-711-dependent downregulation of Ang-1, followed by Akt pathway inhibition, may play a role in neuronal cell death after neuronal injury in vitro and after experimental TBI.