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
A New Panel of Blood Biomarkers for the Diagnosis of Mild Traumatic Brain Injury/Concussion in Adults.
No routine tests currently exist to objectively diagnose mild traumatic brain injury (mTBI)/concussion. Previously reported biomarkers for mTBI represented proteins released from damaged neurons or glia. However, low levels of these proteins, and/or the complexity of assays used for their detection, limits implementation of these biomarkers in routine practice. ⋯ A positive correlation (r=0.681; p<0.001) between plasma levels of LGALS3 and OCLN was also found in mTBI patients, whereas in OI patients or uninjured subjects, these variables did not correlate. This panel of biomarkers discerns, with high accuracy, patients with isolated concussion from uninjured individuals within the first 8 h after accident. These biomarkers can also aid in diagnosing concussion in the presence of OI.
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Journal of neurotrauma · Jan 2016
Serum GFAP predicts tissue GFAP break down products and therapeutic efficacy after penetrating ballistic-like brain injury.
Acute traumatic brain injury (TBI) is associated with neurological dysfunction, changes in brain proteins, and increased serum biomarkers. However, the relationship between these brain proteins and serum biomarkers, and the ability of these serum biomarkers to indicate a neuroprotective/therapeutic response, remains elusive. Penetrating ballistic-like brain injury (PBBI) was used to systematically analyze several key TBI biomarkers, glial fibrillary acidic protein (GFAP) and its break-down products (BDPs)-ubiquitin C-terminal hydrolase-L1 (UCH-L1), α-II spectrin, and α-II spectrin BDPs (SBDPs)-in brain tissues and serum during an extended acute-subacute time-frame. ⋯ Administration of 2.5 mg/kg CsA significantly reduced serum GFAP elevation by 22.4-fold 2 h after PBBI (vs. PBBI+vehicle; p<0.05) and improved neurological function 1 d post-injury. Serum biomarkers, particularly GFAP, may be correlative tools of brain protein changes and feasible theranostic markers of TBI progression and recovery.
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Journal of neurotrauma · Jan 2016
Decompressive Craniectomy increases Brain Lesion Volume and exacerbates Functional Impairment in Closed Head Injury in Mice.
Decompressive craniectomy has been widely used in patients with head trauma. The randomized clinical trial on an early decompression (DECRA) demonstrated that craniectomy did not improve the neurological outcome, in contrast to previous animal experiments. The goal of our study was to analyze the effect of decompressive craniectomy in a murine model of head injury. ⋯ Decompressive craniectomy applied after closed head injury in mice leads to additional structural and functional impairment. The surgical decompression via craniectomy promotes brain edema formation and contusional blossoming in our model. This additive effect of combined mechanical and surgical trauma may explain the results of the DECRA trial and should be explored further in experiments.
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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.