Journal of neurotrauma
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Journal of neurotrauma · Jun 2018
Diminished Dentate Gyrus Filtering of Cortical Input Leads to Enhanced Area Ca3 Excitability after Mild Traumatic Brain Injury.
Mild traumatic brain injury (mTBI) disrupts hippocampal function and can lead to long-lasting episodic memory impairments. The encoding of episodic memories relies on spatial information processing within the hippocampus. As the primary entry point for spatial information into the hippocampus, the dentate gyrus is thought to function as a physiological gate, or filter, of afferent excitation before reaching downstream area Cornu Ammonis (CA3). ⋯ Extracellular recordings and voltage-sensitive dye imaging demonstrated that perforant path activation leads to the aberrant spread of excitation from the dentate gyrus into area CA3 along the mossy fiber pathway. These results suggest that after mTBI, the dentate gyrus has a diminished capacity to regulate cortical input into the hippocampus, leading to increased CA3 network excitability. The loss of the dentate filtering efficacy reveals a potential mechanism by which hippocampal-dependent spatial information processing is disrupted, and may contribute to memory dysfunction after mTBI.
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Journal of neurotrauma · Jun 2018
Clinical TrialMild Jugular Compression Collar Ameliorated Changes in Brain Activation of Working Memory after One Soccer Season in Female High School Athletes.
Recent neuroimaging studies have suggested that repetitive subconcussive head impacts, even after only one sport season, may lead to pre- to post-season structural and functional alterations in male high school football athletes. However, data on female athletes are limited. In the current investigation, we aimed to (1) assess the longitudinal pre- to post-season changes in functional MRI (fMRI) of working memory and working memory performance, (2) quantify the association between the pre- to post-season change in fMRI of working memory and the exposure to head impact and working memory performance, and (3) assess whether wearing a neck collar designed to reduce intracranial slosh via mild compression of the jugular veins can ameliorate the changes in fMRI brain activation observed in the female high school athletes who did not wear collars after a full soccer season. ⋯ A significant pre- to post-season increase in fMRI blood oxygen level dependent (BOLD) signal was demonstrated when performing the N-back working memory task in the non-collar group but not in the collar group, despite the comparable exposure to head impacts during the season between the two groups. The collar group demonstrated significantly smaller pre- to post-season change in fMRI BOLD signal than the non-collar group, suggesting a potential protective effect from the collar device. Significant correlations were also found between the pre- to post-season increase in fMRI brain activation and the decrease in task accuracy in the non-collar group, indicating an association between the compensatory mechanism in underlying neurophysiology and the alteration in the behavioral outcomes.
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Journal of neurotrauma · Jun 2018
Divergent Classification Methods of Post-Concussion Syndrome after Mild Traumatic Brain Injury: Prevalence Rates, Risk Factors, and Functional Outcome.
Mild traumatic brain injury (mTBI) is a common diagnosis and approximately one third of mTBI patients experience a variety of cognitive, emotional, psychosocial, and behavioral post-concussion symptoms. When a cluster of these symptoms persists for more than 3 months they are often classified as post-concussion syndrome (PCS). The objective of this study was to determine prevalence rates, risk factors, and functional outcome associated with PCS 6 months after mTBI, applying divergent classification methods. ⋯ Applying the divergent classification methods resulted in a different set of predictors being statistically significantly associated with PCS, and a different percentage of overlap with functional impairment, measured with the GOSE. In conclusion, depending on the classification method and rating score used, prevalence rates of PCS deviated considerably. For future research, consensus regarding the diagnostic criteria for PCS and the analysis of the RPQ should be reached, to enhance comparability of studies regarding PCS after mTBI.
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Journal of neurotrauma · Jun 2018
Gene Profiling of Nucleus Basalis Tau Containing Neurons in Chronic Traumatic Encephalopathy: A Chronic Effects of Neurotrauma Consortium Study.
Military personnel and athletes exposed to traumatic brain injury may develop chronic traumatic encephalopathy (CTE). Brain pathology in CTE includes intracellular accumulation of abnormally phosphorylated tau proteins (p-tau), the main constituent of neurofibrillary tangles (NFTs). Recently, we found that cholinergic basal forebrain (CBF) neurons within the nucleus basalis of Meynert (nbM), which provide the major cholinergic innervation to the cortex, display an increased number of NFTs across the pathological stages of CTE. ⋯ Specifically, downregulation of the nicotinic cholinergic receptor subunit β-2 gene (CHRNB2), monoaminergic enzymes catechol-O-methyltransferase (COMT) and dopa decarboxylase (DDC), chloride channels CLCN4 and CLCN5, scaffolding protein caveolin 1 (CAV1), cortical development/cytoskeleton element lissencephaly 1 (LIS1), and intracellular signaling cascade member adenylate cyclase 3 (ADCY3) was observed in pS422-immunreactive nbM neurons in CTE patients. By contrast, upregulation of calpain 2 (CAPN2) and microtubule-associated protein 2 (MAP2) transcript levels was found in Stage IV CTE patients. These single-population data in vulnerable neurons indicate alterations in gene expression associated with neurotransmission, signal transduction, the cytoskeleton, cell survival/death signaling, and microtubule dynamics, suggesting novel molecular pathways to target for drug discovery in CTE.
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Journal of neurotrauma · Jun 2018
Reduced Functional Connectivity in Adults with Persistent Post-Concussion Symptoms: A Functional Near-Infrared Spectroscopy Study.
Concussion, or mild traumatic brain injury (mTBI), accounts for ∼80% of all TBIs across North America. The majority of mTBI patients recover within days to weeks; however, 14-36% of the time, acute mTBI symptoms persist for months or even years and develop into persistent post-concussion symptoms (PPCS). There is a need to find biomarkers in patients with PPCS, to improve prognostic ability and to provide insight into the pathophysiology underlying chronic symptoms. ⋯ Specifically, we aimed to identify cortical communication patterns in prefrontal and motor areas during rest and task, in adult patients with persistent symptoms. We found that (1) the PPCS group showed reduced connectivity compared with healthy controls, (2) increased symptom severity correlated with reduced coherence, and (3) connectivity differences were best distinguishable during task and in particular during the working memory task (n-back task) in the right and left dorsolateral prefrontal cortex (DLPFC). These data show that reduced brain communication may be associated with the pathophysiology of mTBI and that fNIRS, with a relatively simple acquisition paradigm, may provide a useful biomarker of this injury.