Journal of neurotrauma
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Journal of neurotrauma · May 2019
Development of Cardiovascular Dysfunction in a Rat Spinal Cord Crush Model and Responses to Serotonergic Interventions.
Selection of a proper spinal cord injury (SCI) rat model to study therapeutic effects of cell transplantation is imperative for research in cardiovascular functional recovery, due to the local harsh milieu inhibiting cell growth. We recently found that a crushed spinal cord lesion can minimize fibrotic scarring and grafted cell death compared with open-dura injuries. To determine if this SCI model is applicable for studying cardiovascular recovery, we examined hemodynamic consequences following crushed SCI and tested cardiovascular responses to serotonin (5-HT) or dopamine (DA) receptor agonists. ⋯ During CRD-induced autonomic dysreflexia, systemic administration of DOI alleviated the severity of bradycardia responsive to episodic hypertension. In contrast, selective stimulation of 5-HT1A receptors with 8-OH-DPAT or non-selective activation of DA receptors with apomorphine did not affect cardiovascular performance. Thus, crush injuries induce cardiovascular abnormalities in rats that are sensitive to 5-HT2A receptor stimulation, indicating a reliable SCI model to study how cell-based approaches impact the severity of autonomic dysreflexia and identify a possible target for pharmacological interventions.
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Journal of neurotrauma · May 2019
Clinical TrialElectrophysiological Guidance of Epidural Electrode Array Implantation over the Human Lumbosacral Spinal Cord to Enable Motor Function after Chronic Paralysis.
Epidural electrical stimulation (EES) of the spinal cord has been shown to restore function after spinal cord injury (SCI). Characterization of EES-evoked motor responses has provided a basic understanding of spinal sensorimotor network activity related to EES-enabled motor activity of the lower extremities. However, the use of EES-evoked motor responses to guide EES system implantation over the spinal cord and their relation to post-operative EES-enabled function in humans with chronic paralysis attributed to SCI has yet to be described. ⋯ Motor response latencies were not significantly different between intraoperative recordings and post-operative recordings, indicating that array positioning remained stable. Additionally, EES enabled intentional control of step-like activity in both subjects within the first 5 days of testing. These results suggest that the use of EES-evoked motor responses may guide intraoperative positioning of epidural electrodes to target spinal cord circuitry to enable motor functions after SCI.
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Journal of neurotrauma · May 2019
Dichotomous locomotor recoveries are predicted by acute changes in segmental blood flow after thoracic spinal contusion injuries in pigs.
Neuroimaging facilitates the translation of animal pre-clinical research to human application. The large porcine spinal cord is useful for testing invasive interventions. Ideally, the safety and efficacy of a delayed intervention is tested in pigs that have recovered sufficiently after spinal cord injury (SCI) to allow either deterioration or improvement of function to be detected. ⋯ There was an inverse association between locomotor outcome and early gray matter hemorrhage on MRI and ultrasound. Epicenter blood flow following contusion predicted recovery or non-recovery of weight-bearing. The depth of the dorsal cerebrospinal fluid space, which varied between animals, influenced injury severity and confounded the results in this fixed-stroke paradigm.
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Journal of neurotrauma · May 2019
Predictors of response to 4-aminopyridine in chronic canine spinal cord injury.
4-Aminopyridine (4AP), a potassium channel antagonist, can improve hindlimb motor function in dogs with chronic thoracolumbar spinal cord injury (SCI); however, individual response is variable. We hypothesized that injury characteristics would differ between dogs that do and do not respond to 4AP. Our objective was to compare clinical, electrodiagnostic, gait, and imaging variables between dogs that do and do not respond to 4AP, to identify predictors of response. ⋯ MEPs were more common post-4AP than pre-4AP (10 vs. 6 dogs) and 4AP decreased H-reflex threshold and increased spasticity in responders. 4-AP impacts central conduction and motor neuron pool excitability in dogs with chronic SCI. Severity of spasticity and H-reflex threshold might allow prediction of response. Further exploration of electrodiagnostic and imaging characteristics might elucidate additional factors contributing to response or non-response.