Journal of neurotrauma
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Journal of neurotrauma · Aug 2021
Pharmacological inhibition of soluble tumor necrosis factor-alpha (sTNFα) 2 weeks after high thoracic spinal cord injury does not affect sympathetic hyperreflexia.
After a severe, high-level spinal cord injury (SCI), plasticity to intraspinal circuits below injury results in heightened spinal sympathetic reflex activity and detrimentally impacts peripheral organ systems. Such sympathetic hyperreflexia is immediately apparent as an episode of autonomic dysreflexia (AD), a life-threatening condition characterized by sudden hypertension and reflexive bradycardia following below-level sensory inputs; for example, pressure sores or impacted fecal matter. Over time, plasticity within the spinal sympathetic reflex (SSR) circuit contributes to the progressive intensification of AD events, as the frequency and severity of AD events increase greatly beginning ∼2 weeks post-injury (wpi). ⋯ We examined the severity of colorectal distension-induced AD biweekly. We found that initiation of sTNFα inhibition at 2 wpi does not attenuate the severity or intensification of sympathetic hyperreflexia compared with saline-treated controls. Coupled with previous data from our group, these findings suggest that central sTNFα signaling must be targeted prior to 2 weeks post-SCI in order to decrease sympathetic hyperreflexia.
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Journal of neurotrauma · Aug 2021
Local and systemic factors drive ectopic osteogenesis in regenerating muscles of spinal cord-injured mice in a lesion level-dependent manner.
Neuroimmune dysfunction is thought to promote the development of several acute and chronic complications in spinal cord injury (SCI) patients. Putative roles for adrenal stress hormones and catecholamines are increasingly being recognized, yet how these adversely affect peripheral tissue homeostasis and repair under SCI conditions remains elusive. ⋯ This cascade of events is shown to critically involve adrenergic signals and drive the acute release of the neuropeptide, substance P. Our findings generate new insights into the kinetics and processes that govern SCI-induced deregulations in skeletal muscle homeostasis and regeneration, thereby aiding the development of sequential therapeutic strategies that can prevent or attenuate neuromusculoskeletal complications in SCI patients.
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Journal of neurotrauma · Aug 2021
Randomized Controlled TrialA Randomized Controlled Trial of Local Delivery of a Rho-Inhibitor (VX-210) in Patients With Acute Traumatic Cervical Spinal Cord Injury.
Acute traumatic spinal cord injury (SCI) can result in severe, lifelong neurological deficits. After SCI, Rho activation contributes to collapse of axonal growth cones, failure of axonal regeneration, and neuronal loss. This randomized, double-blind, placebo-controlled phase 2b/3 study evaluated the efficacy and safety of Rho inhibitor VX-210 (9 mg) in patients after acute traumatic cervical SCI. ⋯ The pre-defined futility stopping rule was met, and the study was therefore ended prematurely. In the final analysis, the primary efficacy end-point was not met, with no statistically significant difference in change from baseline in upper-extremity motor score at 6 months after treatment between the VX-210 (9-mg) and placebo groups. This work opens the door to further improvements in the design and conduct of clinical trials in acute SCI.
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Journal of neurotrauma · Aug 2021
Efficacy of Early (<=24 hours), Late (25-72 hours), and Delayed (>72 hours) Surgery with MRI-Confirmed Decompression in AIS grades C, D, Acute Traumatic Central Cord Syndrome Due to Spinal Stenosis.
The therapeutic significance of timing of decompression in acute traumatic central cord syndrome (ATCCS) caused by spinal stenosis remains unsettled. We retrospectively examined a homogenous cohort of patients with ATCCS and magnetic resonance imaging (MRI) evidence of post-treatment spinal cord decompression to determine whether timing of decompression played a significant role in American Spinal Injury Association (ASIA) motor score (AMS) 6 months following trauma. We used the t test, analysis of variance, Pearson correlation coefficient, and multiple regression for statistical analysis. ⋯ There was no significant effect of the timing of decompression on follow-up AMS. Only AMS at admission determined AMS at follow-up (coefficient = 0.31; 95% confidence interval [CI]:0.21; p = 0.001). We conclude that timing of decompression in ATCCS caused by spinal stenosis has little bearing on ultimate AMS at follow-up.
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Journal of neurotrauma · Aug 2021
Diaphragm motor evoked potential induced by cervical magnetic stimulation following cervical spinal cord contusion in the rat.
Cervical spinal injury is typically associated with respiratory impairments due to damage to bulbospinal respiratory pathways and phrenic motoneurons. Magnetic stimulation is a non-invasive approach for the evaluation and modulation of the nervous system. The present study was designed to examine whether cervical magnetic stimulation can be applied to evaluate diaphragmatic motor outputs in a pre-clinical rat model of cervical spinal injury. ⋯ However, the threshold of the diaphragmatic motor-evoked potential was reduced, and the amplitude of the diaphragmatic motor-evoked potential was enhanced in response to cervical magnetic stimulation at the acute injury stage. Moreover, the motor-evoked potentials of the bilateral diaphragm in animals with contusions were generally larger when the coil was placed at the left spinal cord at the subchronic and chronic injury stages. These results suggested that cervical magnetic stimulation can be used to examine the excitability of phrenic motor outputs post-injury, and magnetic stimulation applied more laterally may be more effective for triggering diaphragmatic motor-evoked potentials.