Journal of neurotrauma
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Journal of neurotrauma · Mar 2019
Pharmacological stimulation of mitochondrial biogenesis using the FDA-approved β2-adrenoreceptor agonist formoterol for the treatment of spinal cord injury.
A hallmark of the progressive cascade of damage referred to as secondary spinal cord injury (SCI) is vascular disruption resulting in decreased oxygen delivery and loss of mitochondria homeostasis. While therapeutics targeting restoration of single facets of mitochondrial function have proven largely ineffective clinically post-SCI, comprehensively addressing mitochondrial function via pharmacological stimulation of mitochondrial biogenesis (MB) is an underexplored strategy. This study examined the effects of formoterol, a mitochondrial biogenic Food and Drug Administration-approved selective and potent β2-adrenoreceptor (ADRB2) agonist, on recovery from SCI in mice. ⋯ Importantly, locomotor capability of formoterol-treated mice was greater than vehicle-treated mice by 7 days, reaching a Basso Mouse Scale score two points greater than that of vehicle-treated SCI mice by 15 days. Interestingly, similar locomotor restoration was observed when initiation of treatment was delayed until 8 h post-injury. These data provide evidence of ADRB2-mediated MB as a therapeutic approach for the management of SCI.
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Journal of neurotrauma · Mar 2019
Experimental Spinal Cord Injury Causes Left-Ventricular Atrophy and Is Associated with an Upregulation of Proteolytic Pathways.
Spinal cord injury (SCI) causes autonomic dysfunction, altered neurohumoral control, profound hemodynamic changes, and an increased risk of heart disease. In this prospective study, we investigated the cardiac consequences of chronic experimental SCI in rats by combining cutting edge in vivo techniques (magnetic resonance imaging [MRI] and left-ventricular [LV] pressure-volume catheterization) with histological and molecular assessments. Twelve weeks post-SCI, MRI-derived structural indices and in vivo LV catheterization-derived functional indices indicated the presence of LV atrophy (LV mass in Control vs. ⋯ At the cellular level, we found the presence of reduced cardiomyocyte size and increased expression of angiotensin II type 1 receptors and transforming growth factor-beta receptors (TGF-β receptor 1 and 2) post-SCI. Importantly, we found more than a two-fold increase in muscle ring finger-1 and Beclin-1 protein level following SCI, indicating the upregulation of the ubiquitin-proteasome system and autophagy-lysosomal machinery. Our data provide novel evidence that SCI-induced cardiomyocyte atrophy and systolic cardiac dysfunction are accompanied by an upregulation of proteolytic pathways, the activation of which is likely due to loss of trophic support from the sympathetic nervous system, neuromechanical unloading, and altered neurohumoral pathways.
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Journal of neurotrauma · Mar 2019
Observational StudyNon-Invasive Pressure Reactivity Index Using Doppler Systolic Flow Parameters: A Pilot Analysis.
The goal was to predict pressure reactivity index (PRx) using non-invasive transcranial Doppler (TCD) based indices of cerebrovascular reactivity, systolic flow index (Sx_a), and mean flow index (Mx_a). Continuous extended duration time series recordings of middle cerebral artery cerebral blood flow velocity (CBFV) were obtained using robotic TCD in parallel with direct intracranial pressure (ICP). PRx, Sx_a, and Mx_a were derived from high frequency archived signals. ⋯ With application of ARIMA and LME modeling, it is possible to predict PRx using non-invasive TCD measures. These are the first and as well as being preliminary attempts at doing so. Much further work is required.
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Journal of neurotrauma · Mar 2019
Randomized Controlled TrialImpact of Low-Level Blast Exposure on Brain Function after a One-Day Tactile Training and the Ameliorating Effect of a Jugular Vein Compression Neck Collar Device.
Special Weapons and Tactics (SWAT) personnel who conduct breacher exercises are at risk for blast-related head trauma. We aimed to investigate the potential impact of low-level blast exposure during breacher training on the neural functioning of working memory and auditory network connectivity. We also aimed to evaluate the effects of a jugular vein compression collar, designed to internally mitigate slosh energy absorption, preserving neural functioning and connectivity, following blast exposure. ⋯ The elevation in fMRI activation in the non-collar group was found to correlate significantly (n = 7, r = 0.943, p = 0.001) with average peak impulse amplitude experienced during the training. In the resting-state fMRI analysis, significant pre- to post-training increase in connectivity between the auditory network and two discrete regions (left middle frontal gyrus and left superior lateral occipital/angular gyri) was found in the non-collar group, while no change was observed in the collar group. These data provided initial evidence of the impact of low-level blast on working memory and auditory network connectivity as well as the protective effect of collar on brain function following blast exposure, and is congruent with previous collar findings in sport-related traumatic brain injury.