Journal of neurotrauma
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Journal of neurotrauma · Jan 2016
Traumatic Brain Injury Impairs SNARE Complex Formation and Alters Synaptic Vesicle Distribution in the Hippocampus.
Traumatic brain injury (TBI) impairs neuronal function and can culminate in lasting cognitive impairment. While impaired neurotransmitter release has been well established after experimental TBI, little is understood about the mechanisms underlying this consequence. In the synapse, vesicular docking and neurotransmitter release requires the formation of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex. ⋯ Synapses in the hippocampus were imaged at 100k magnification, and vesicle distribution was assessed in pre-synaptic terminals at the active zone. CCI resulted in a significant reduction in vesicle number within 150 nm of the active zone. These findings provide the first evidence of TBI-induced impairments in synaptic vesicle docking, and suggest that reductions in the pool of readily releasable vesicles and impaired SNARE complex formation are two novel mechanisms contributing to impaired neurotransmission after TBI.
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Journal of neurotrauma · Jan 2016
Susceptibility Weighted Imaging and Mapping of Micro-hemorrhages and Major Deep Veins after Traumatic Brain Injury.
Micro-hemorrhages are a common result of traumatic brain injury (TBI), which can be quantified with susceptibility weighted imaging and mapping (SWIM), a quantitative susceptibility mapping approach. A total of 23 TBI patients (five women, 18 men; median age, 41.25 years old; range, 21.69-67.75 years) with an average Glasgow Coma Scale score of 7 (range, 3-15) at admission were recruited at mean 149 d (range, 57-366) after injury. Susceptibility-weighted imaging data were collected and post-processed to create SWIM images. ⋯ With different thresholds (250, 227 and 200 ppb), the specificity was 97%, 95%, and 92%, and the sensitivity was 84%, 90%, and 92%, respectively. These results show that SWIM could be used to differentiate hemorrhages from veins in TBI patients in a semi-automated manner with reasonable sensitivity and specificity. A larger cohort will be needed to validate these findings.
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Previous studies report that cavum septum pellucidum (CSP) is frequent among athletes with a history of repeated traumatic brain injury (TBI), such as boxers. Few studies of CSP in athletes, however, have assessed detailed features of the septum pellucidum in a case-control fashion. This is important because prevalence of CSP in the general population varies widely (2% to 85%) between studies. ⋯ Sixteen of 17 (94%) players had a CSP graded ≥2 compared with 3 of 17 (18%) controls. CSP was significantly higher grade (p<0.001) and longer in players than controls (mean length±standard deviation: 10.6 mm±5.4 vs. 1.1 mm±1.3, p<0.001). Among patients presenting to a memory clinic, long high-grade CSP was more frequent in retired pro-football players compared with patients without a history of TBI.
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Journal of neurotrauma · Jan 2016
Combination Therapies for Traumatic Brain Injury: Retrospective Considerations.
Patients enrolled in clinical trials for traumatic brain injury (TBI) may present with heterogeneous features over a range of injury severity, such as diffuse axonal injury, ischemia, edema, hemorrhage, oxidative damage, mitochondrial and metabolic dysfunction, excitotoxicity, inflammation, and other pathophysiological processes. To determine whether combination therapies might be more effective than monotherapy at attenuating moderate TBI or promoting recovery, the National Institutes of Health funded six preclinical studies in adult and immature male rats to evaluate promising acute treatments alone and in combination. ⋯ One study demonstrated worse results with the combination in comparison with monotherapies. While specific research findings are reported elsewhere, this article provides an overview of the study designs, insights, and recommendations for future research aimed at therapy development for TBI.