Journal of neurotrauma
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Journal of neurotrauma · Dec 2017
PROCHLORPERAZINE INCREASES KCC2 FUNCTION AND REDUCES SPASTICITY AFTER SPINAL CORD INJURY.
In mature neurons, low intracellular chloride level required for inhibition is maintained by the potassium-chloride cotransporter, KCC2. Impairment of Cl- extrusion after KCC2 dysfunction has been involved in many central nervous system disorders, such as seizures, neuropathic pain, or spasticity, after a spinal cord injury (SCI). This makes KCC2 an appealing drug target for restoring Cl- homeostasis and inhibition in pathological conditions. ⋯ Among them, prochlorperazine hyperpolarizes the Cl- equilibrium potential in motoneurons of neonatal rats and restores the reciprocal inhibition post-SCI. The compound alleviates spasticity in chronic adult SCI rats with an efficacy equivalent to the antispastic agent, baclofen, and rescues the SCI-induced downregulation of KCC2 in motoneurons below the lesion. These pre-clinical data support prochlorperazine for a new therapeutic indication in the treatment of spasticity post-SCI and neurological disorders involving a KCC2 dysfunction.
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Journal of neurotrauma · Dec 2017
ReviewThe Effects of Glial Cell Line-Derived Neurotrophic Factor After Spinal Cord Injury.
Spinal cord injury (SCI) is a devastating condition affecting 270,000 people in the United States. The use of growth factors is a potential treatment for reducing secondary damage, promoting axon growth, and restoring some of the lost function post-SCI. Glial cell line-derived neurotrophic factor (GDNF) is an important growth factor, because it can affect both neurons and support cells. ⋯ Several different types of genetically modified cells have been used with varying success. Although GDNF is effective when used alone, it has been shown to be more effective when used in combination with other neurotrophic factors. Overall, GDNF significantly improved functional recovery, increased the number of sprouting neurons, reduced lesion size at the injury site, and had minimal adverse effects.
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Journal of neurotrauma · Dec 2017
Early complications, morbidity, and mortality in octo- and nonagenarians undergoing posterior intraoperative spinal navigation-based C1/2 fusion for type II odontoid process fractures.
Type II odontoid fractures represent the most common cervical spine injury in the elderly. The decision for surgical treatment is still controversial, particularly with regard to the elevated peri-operative risk attributed to frequent comorbidities and poor bone quality. The purpose of this study was to assess both short-term mortality and mid-term clinical and radiological outcome in the elderly. ⋯ Atlanto-axial fusion by using intra-operative spinal navigation is a safe and effective procedure in the elderly, with few complications and preservation of favorable post-operative quality of life. The overall major complication rate was 11%. Surgery in the very old should be considered as first-choice treatment.
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Journal of neurotrauma · Dec 2017
Impaired baroreflex function during orthostatic challenge in patients after spinal cord injury.
The level of spinal cord injury (SCI) affects baroreflex regulation of blood pressure. While a parasympathetic cardiac chronotropic effect is preserved, baroreflex response could be impaired by sympathetic dysfunction under the SCI level. This study was aimed to evaluate the baroreflex function in SCI patients by the analysis of causal interaction between systolic blood pressure (SBP) and inter-beat intervals (IBI). ⋯ In conclusion, baroreflex dysfunction in SCI patients was detected using causal analysis methods during orthostatic challenge only. Baroreflex dysfunction is probably an important mechanism of the more expressed blood pressure decrease associated with CSCI. The severity of autonomic dysfunction was related to SCI level.
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Journal of neurotrauma · Dec 2017
Changes in Pressure, Hemodynamics and Metabolism Within the Spinal Cord During the First 7-days After Injury Using a Porcine Model.
Traumatic spinal cord injury (SCI) triggers many perturbations within the injured cord, such as decreased perfusion, reduced tissue oxygenation, increased hydrostatic pressure, and disrupted bioenergetics. While much attention is directed to neuroprotective interventions that might alleviate these early pathophysiologic responses to traumatic injury, the temporo-spatial characteristics of these responses within the injured cord are not well documented. In this study, we utilized our Yucatan mini-pig model of traumatic SCI to characterize intraparenchymal hemodynamic and metabolic changes within the spinal cord for 1 week post-injury. ⋯ Taken together, traumatic SCI resulted in an expanding area of ischemia/hypoxia, with ongoing physiological perturbations sustained out to 7 days post-injury. This suggests that our clinical practice of hemodynamically supporting patients out to 7 days post-injury may fail to address persistent ischemia within the injured cord. A detailed understanding of these pathophysiological mechanisms after SCI is essential to promote best practices for acute SCI patients.