Experimental neurology
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Experimental neurology · Jul 2014
Randomized Controlled TrialN-acetylcysteine amide preserves mitochondrial bioenergetics and improves functional recovery following spinal trauma.
Mitochondrial dysfunction is becoming a pivotal target for neuroprotective strategies following contusion spinal cord injury (SCI) and the pharmacological compounds that maintain mitochondrial function confer neuroprotection and improve long-term hindlimb function after injury. In the current study we evaluated the efficacy of cell-permeating thiol, N-acetylcysteine amide (NACA), a precursor of endogenous antioxidant glutathione (GSH), on mitochondrial function acutely, and long-term tissue sparing and hindlimb locomotor recovery following upper lumbar contusion SCI. Some designated injured adult female Sprague-Dawley rats (n=120) received either vehicle or NACA (75, 150, 300 or 600mg/kg) at 15min and 6h post-injury. ⋯ Other designated injured rats (n=21) received continuous NACA (150 or 300mg/kg/day) treatment starting at 15min post-injury for one week to assess long-term functional recovery over 6weeks post-injury. Locomotor testing and novel gait analyses showed significantly improved hindlimb function with NACA that were associated with increased tissue sparing at the injury site. Overall, NACA treatment significantly maintained acute mitochondrial bioenergetics and normalized GSH levels following SCI, and prolonged delivery resulted in significant tissue sparing and improved recovery of hindlimb function.
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Experimental neurology · Apr 2014
Randomized Controlled TrialDecision-making under risk is improved by both dopaminergic medication and subthalamic stimulation in Parkinson's disease.
Inconsistent findings regarding the effects of dopaminergic medication (MED) and deep brain stimulation (DBS) of the subthalamic nucleus (STN) on decision making processes and impulsivity in Parkinson's disease (PD) patients have been reported. This study investigated the influence of MED and STN-DBS on decision-making under risk. Eighteen non-demented PD patients, treated with both MED and STN-DBS (64.3±10.2years, UPDRS III MED off, DBS off 45.5±17.1) were tested with the Game of Dice Task (GDT) which probes decision-making under risk during four conditions: MED on/DBS on, MED on/DBS off, MED off/DBS on, and MED off/DBS off. ⋯ Significantly higher GDT net scores were observed in Med on in contrast to Med off conditions as well as in DBS on versus DBS off conditions. However, no effect of therapy for the patient's ability to make use of negative feedback could be detected. The data suggest a positive influence of both MED and STN-DBS on making decisions under risk in PD patients, an effect which seems to be mediated by mechanisms other than the use of negative feedback.
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Experimental neurology · Nov 2013
Randomized Controlled TrialAntidepressant effects after short-term and chronic stimulation of the subgenual cingulate gyrus in treatment-resistant depression.
Deep brain stimulation (DBS) of the subcallosal cingulate gyrus (SCG) is an experimental approach in treatment-resistant depression (TRD). Apart from its potential long-term antidepressant effects acute stimulation effects have been described. We investigated putative neuroanatomical clusters in which such acute effects accumulate and followed patients over the long-term. ⋯ Our results confirm that stimulation of the SCG is capable of exerting moderate acute and chronic antidepressant effects. The predictive value of these findings needs to be addressed in future studies.
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Experimental neurology · Dec 2012
Randomized Controlled TrialTreatment of rats with pioglitazone in the reperfusion phase of focal cerebral ischemia: a preclinical stroke trial.
Thiazolidinediones (TZDs), pioglitazone, rosiglitazone and troglitazone, the synthetic agonists for the PPARγ, administered prior or during ischemic insult improve stroke outcome in rodents, post-occlusion treatments yielded inconsistent results. In the present experiments carried out according to the Stroke Therapy Academic Industry Roundtable (STAIR) guidelines, we studied the effects of post-ischemic pioglitazone treatment on the outcome of focal cerebral ischemia, inflammatory and apoptotic processes, neuronal degeneration and regeneration, blood pressure, heart rate and physiological variables in blood. Male Wistar rats were subjected to a 90 min middle cerebral artery occlusion (MCAO). ⋯ The current results provide evidence that pioglitazone treatment in the post-ischemic, reperfusion phase improves the recovery from ischemic stroke. Neuroprotective effects of pioglitazone are mediated by inhibition of post-ischemic inflammation and neuronal degeneration, protection of neurones against ischemic injury and by promoting of neuronal regeneration. Our data together with previous findings favour the view that pioglitazone is a promising candidate for clinical stroke trials.
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Experimental neurology · May 2007
Randomized Controlled TrialReaction to topical capsaicin in spinal cord injury patients with and without central pain.
Central neuropathic pain is a debilitating and frequent complication to spinal cord injury (SCI). Excitatory input from hyperexcitable cells around the injured grey matter zone is suggested to play a role for central neuropathic pain felt below the level of a spinal cord injury. Direct evidence for this hypothesis is difficult to obtain. ⋯ Touch, punctuate stimuli, cold stimuli and topical capsaicin was applied above, at, and below injury level in 10 SCI patients with central pain below a thoracic injury, in 10 SCI patients with a thoracic injury but without neuropathic pain, and in corresponding areas in 10 healthy control subjects. The study found increased responses to touch at injury level compared to controls (p=0.033) and repetitive punctuate stimuli above and at injury level compared to controls and pain-free SCI patients (p<0.04) but not an increased response to capsaicin in patients with central pain. These results suggest that SCI patients with below-level pain have increased responses to some but not all sensory input at the level of injury.