Experimental neurology
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Experimental neurology · Apr 2009
Case ReportsMexiletine-responsive erythromelalgia due to a new Na(v)1.7 mutation showing use-dependent current fall-off.
Inherited erythromelalgia (IEM), characterized by episodic burning pain and erythema of the extremities, is produced by gain-of-function mutations in sodium channel Na(v)1.7, which is preferentially expressed in nociceptive and sympathetic neurons. Most patients do not respond to pharmacotherapy, although occasional reports document patients as showing partial relief with lidocaine or mexiletine. A 7-year-old girl, with a two-year history of symmetric burning pain and erythema in her hands and feet, was diagnosed with erythromelalgia. ⋯ We observed a stronger use-dependent fall-off in current following exposure to mexiletine for V872G compared to wild-type channels. These observations suggest that some patients with IEM may show a favorable response to mexiletine due to a use-dependent effect on mutant Na(v)1.7 channels. Continued relief from pain, even after mexiletine was discontinued in this patient, might suggest that early treatment may slow the progression of the disease.
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Experimental neurology · Apr 2009
Clinical TrialSaccadometry: a novel clinical tool for quantification of the motor effects of subthalamic nucleus stimulation in Parkinson's disease.
High frequency stimulation of the subthalamic nucleus (STN HFS) is the therapy of choice in the surgical management of patients suffering from advanced Parkinson's disease (PD). Worldwide, more than 30,000 patients have undergone this procedure. At present, there is a need for a rapid method of assessing its therapeutic effect that is ideally also target-specific, objective, automated, quantitative, and with high overall reliability. Saccadic latency, that reflects the operation of central decision-making mechanisms, is increasingly being used as a way of obtaining quantitative, objective information about cerebral performance in general. ⋯ A possible interpretation of our findings is that electrical stimulation of the STN, which is known to have a powerful influence on substantia nigra pars reticulata, enhances both the descending facilitation that passes from the cortex to the colliculus via the basal ganglia, thus increasing the mean rate of rise of the decision signal, and also the tonic background inhibition that normally suppresses unwanted early responses.
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Experimental neurology · Apr 2009
Better functional outcome of compression spinal cord injury in mice is associated with enhanced H-reflex responses.
Alterations in spinal reflexes and functional improvements occur after incomplete spinal cord injury but the relationship between these phenomena is not understood. Here we show that spontaneous functional recovery after compression injury of the spinal cord at low-thoracic level (Th10-12) in C57BL/6J mice is associated with a progressively increasing, over 3 months, excitability of the plantar H-reflex. The stimulation rate-sensitive H-reflex depression, already strongly reduced at 1 week after injury, when compared with non-injured mice, decreased further during the observation time period. ⋯ Enhanced H-reflex responses at frequencies between 0.1 and 5 Hz were also observed in mice deficient in the extracellular matrix glycoprotein tenascin-R and the adhesion molecule close homolog of L1, mice previously shown to have better motor recovery after spinal cord injury than wild-type littermates. These results indicate that better functional outcome of compression spinal cord injury in mice is associated with alterations of the monosynaptic reflex pathway which facilitate motoneuron recruitment. Our observations support the view that plasticity of spinal circuitries underlies specific aspects of motor recovery and demonstrate the usefulness of H-reflex analyses in studies on spinal cord injury in mice.
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Experimental neurology · Apr 2009
Simvastatin reduces secondary brain injury caused by cortical contusion in rats: possible involvement of TLR4/NF-kappaB pathway.
Simvastatin, a cholesterol-lowering agent, has demonstrated neuroprotective effects against brain injury, but the underlying mechanisms remain unclear. This study was undertaken to evaluate the effect of simvastatin on the Toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-kappaB) related signaling pathway and secondary brain injury in rats after traumatic brain injury (TBI). Adult male Wistar rats were divided into four groups: (1) Sham group (n=25); (2) Sham+vehicle group (n=25); (3) TBI+vehicle group (n=30); and (4) TBI+simvastatin group (n=30). ⋯ As a result, we found that treatment with simvastatin markedly inhibited the mRNA and protein expressions of TLR4, NF-kappaB and the downstream inflammatory agents, such as interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and intercellular adhesion molecule-1 (ICAM-1). Administration of simvastatin following TBI significantly ameliorated the secondary brain damage, such as cortical apoptosis, brain edema, blood-brain barrier (BBB) impairment, and motor deficits. In conclusion, post-TBI simvastatin administration may attenuate TLR4/NF-kappaB-mediated inflammatory response in the injured rat brain, and this may be one mechanism by which simvastatin improves outcome following TBI.
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Experimental neurology · Mar 2009
Treadmill training enhances the recovery of normal stepping patterns in spinal cord contused rats.
Treadmill training is known to improve stepping in complete spinal cord injured animals. Few studies have examined whether treadmill training also enhances locomotor recovery in animals following incomplete spinal cord injuries. In the present study, we compared locomotor recovery in trained and untrained rats that received a severe mid-thoracic contusion of the spinal cord. ⋯ In contrast, untrained rats executed step cycles that consisted of fast, kick-like movements during forward swing. These findings indicate that spinal cord contused rats can generate partial weight bearing stepping in the absence of treadmill training. The findings also suggest that the effect of treadmill training is to restore normal patterns of hindlimb movements following severe incomplete spinal cord injury in rats.