Experimental neurology
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Experimental neurology · Sep 2013
Functional consequences of ethidium bromide demyelination of the mouse ventral spinal cord.
Ethidium bromide (EB) has been extensively used in the rat as a model of spinal cord demyelination. However, this lesion has not been addressed in the adult mouse, a model with unlimited genetic potential. Here we characterize behavioral function, inflammation, myelin status and axonal viability following bilateral injection of 0.20 mg/mL ethidium bromide or saline into the ventral white matter (VWM) of female C57Bl/6 mice. ⋯ As these data suggest that EB-injection in the mouse spinal cord is a non-remyelinating lesion, we sought to ask whether wheel running could promote recovery by enhancing plasticity of local lumbar circuitry independent of remyelination. This did not occur as BMS and Treadscan assessment revealed no significant effect of wheel running on recovery. However, this study defines the importance of descending ventral motor pathways to locomotor function in the mouse as VWM loss results in a chronic hindlimb deficit.
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Experimental neurology · Sep 2013
Mindin is a critical mediator of ischemic brain injury in an experimental stroke model.
Stroke is the second leading cause of death among adults worldwide. Mindin is an ECM protein that plays important roles in regulating inflammation, angiogenesis and neuronal outgrowth. The role of mindin in the context of brain ischemia has not been examined. ⋯ Mindin KO mice exhibited minor infarctions, an attenuated inflammatory response and low levels of neuronal apoptosis following an ischemic insult. These data demonstrate that mindin is a critical mediator of ischemic brain injury in an experimental stroke model. Akt signaling most likely mediates the biological function of mindin in this model of cerebral ischemia.
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Experimental neurology · Sep 2013
Increased SMA-M1 coherence in Parkinson's disease - Pathophysiology or compensation?
Parkinson's disease (PD) is a common neurodegenerative disorder owing to loss of dopaminergic cells. Akinesia - one of the core symptoms of PD - is associated with exaggerated oscillations at beta frequency (13-30 Hz) within the subthalamic nucleus (STN). Thus, enhanced oscillations below 30 Hz are assumed to represent a pathophysiological marker of PD. ⋯ During rest a significant positive correlation between disease duration and SMA-M1 coherence was found ON but not OFF medication. Conversely, during isometric contraction SMA-M1 coherence and UPDRS III were inversely correlated OFF but not ON medication explaining more than 80% of variance. The results favor the hypothesis that OFF medication exaggerated cortical coherence at beta frequency represents a compensatory mechanism rather than a pathophysiological marker per se.
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Experimental neurology · Sep 2013
Cutaneous noradrenaline measured by microdialysis in complex regional pain syndrome during whole-body cooling and heating.
Complex regional pain syndrome (CRPS) is characterised by autonomic, sensory, and motor disturbances. The underlying mechanisms of the autonomic changes in CPRS are unknown. However, it has been postulated that sympathetic inhibition in the acute phase with locally reduced levels of noradrenaline is followed by an up-regulation of alpha-adrenoceptors in chronic CRPS leading to denervation supersensitivity to catecholamines. ⋯ CRPS pain and the perceived skin temperature were measured every 5 min during thermal exposure, while noradrenaline was determined from cutaneous microdialysate collected every 20 min throughout the study period. Cooling induced peripheral sympathetic activation in patients and controls with significant increases in dermal noradrenaline, vasoconstriction, and reduction in skin temperature. The main findings were that the noradrenaline response did not differ between patients and controls or between the CRPS hand and the contralateral unaffected hand, suggesting that the evoked noradrenaline release from the cutaneous sympathetic postganglionic fibres is preserved in chronic CRPS patients.
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Experimental neurology · Sep 2013
Interleukin-10 down-regulates voltage gated sodium channels in rat dorsal root ganglion neurons.
The over-expression of voltage-gated sodium channels (VGSCs) in dorsal root ganglion (DRG) neurons following peripheral nerve injury contributes to neuropathic pain by generation of the ectopic discharges of action potentials. However, mechanisms underlying the change in VGSCs' expression are poorly understood. Our previous work has demonstrated that the pro-inflammatory cytokine TNF-α up-regulates VGSCs. ⋯ Consistent with the electrophysiological results, real-time PCR and western blot revealed that IL-10 (200 pg/ml) down-regulated VGSCs in both mRNA and protein levels and reversed the up-regulation of VGSCs by TNF-α. Moreover, repetitive intrathecal administration of rrIL-10 for 3 days (4 times per day) attenuated mechanical allodynia in L5 spinal nerve ligation model and profoundly inhibited the excitability of DRG neurons. These results suggested that the down-regulation of the sodium channels in DRG neurons might contribute to the therapeutic effect of IL-10 on neuropathic pain.