Experimental neurology
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Experimental neurology · Jul 2011
Deep brain stimulation of the ventral intermediate nucleus in patients with essential tremor: stimulation below intercommissural line is more efficient but equally effective as stimulation above.
The posterior subthalamic area (PSA), ventral to the intercommissural line (ICL) and the ventral intermediate nucleus (VIM), has been suggested as a promising target for deep brain stimulation (DBS) in patients suffering from essential tremor (ET). In this study the clinical benefit of VIM and PSA DBS on postural tremor suppression was systematically evaluated in a two step approach with a 3D ultrasound kinematic analysis tool. ⋯ The data suggest that sub-ICL stimulation may be more efficient compared to thalamic stimulation but equally effective when patients' individual stimulation parameters are used.
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Experimental neurology · Jun 2011
High frequency oscillations in the subthalamic nucleus: a neurophysiological marker of the motor state in Parkinson's disease.
Increasing evidence suggests that abnormal oscillatory activity in basal ganglia and cortex plays a pivotal role in the pathophysiology of Parkinson's disease. Recordings of local field potentials from subthalamic nucleus of patients undergoing deep brain stimulation have focused on oscillations occurring at frequencies below 100 Hz in the alpha, beta and gamma range and suggested that, in particular, an increase of beta band oscillations underlies slowing of movement in Parkinson's disease. Recent findings showing that the amplitude of high frequency oscillations (>200 Hz) couples with the phase of beta activity have raised the important question about the role of subthalamic high frequency oscillations in Parkinson's disease. ⋯ Moreover, this power ratio correlated significantly with the Unified Parkinson's Disease Rating Scale hemibody akinesia/rigidity subscore (r=0.3618, p=0.015), but interestingly not with beta peak power (p=0.1) suggesting that levodopa induced changes in high frequency and beta oscillations are at least potentially independent of each other. Accordingly, a combined parameter composed of power ratio of high frequency oscillations and beta peak power significantly increased the correlation with the motor state (r=0.45, p=0.004). These results indicate that a shift from slower to faster frequencies of the spectrum greater than 200 Hz represents a prokinetic neurophysiological marker underlying levodopa induced motor improvement in Parkinson's disease.
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Experimental neurology · Jun 2011
Local modulation of striatal glutamate efflux by serotonin 1A receptor stimulation in dyskinetic, hemiparkinsonian rats.
Serotonin 1A receptor (5-HT(1A)R) agonists reduce both L-DOPA- and D1 receptor (D1R) agonist-mediated dyskinesia, but their anti-dyskinetic mechanism of action is not fully understood. Given that 5-HT(1A)R stimulation reduces glutamatergic neurotransmission in the dopamine-depleted striatum, 5-HT(1A)R agonists may diminish dyskinesia in part through modulation of pro-dyskinetic striatal glutamate levels. To test this, rats with unilateral medial forebrain bundle dopamine or sham lesions were primed with L-DOPA (12 mg/kg+benserazide, 15 mg/kg, sc) or the D1R agonist SKF81297 (0.8 mg/kg, sc) until abnormal involuntary movements (AIMs) stabilized. ⋯ Systemic and striatal ±8-OH-DPAT attenuated L-DOPA-induced dyskinesia and striatal glutamate efflux while WAY100635 reversed ±8-OH-DPAT's effects. Interestingly, systemic ±8-OH-DPAT diminished D1R-mediated AIMs without affecting glutamate. These findings indicate a novel anti-dyskinetic mechanism of action for 5-HT(1A)R agonists with implications for the improved treatment of Parkinson's disease.
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Experimental neurology · Jun 2011
The dopamine and cAMP regulated phosphoprotein, 32 kDa (DARPP-32) signaling pathway: a novel therapeutic target in traumatic brain injury.
Traumatic brain injury (TBI) causes persistent neurologic deficits. Current therapies, predominantly focused upon cortical and hippocampal cellular survival, have limited benefit on cognitive outcomes. Striatal damage is associated with deficits in executive function, learning, and memory. ⋯ Amantadine, shown to be efficacious in treating post-TBI cognitive deficits, given daily for two weeks is able to restore the loss of DARPP-32 phosphorylation and reduce protein phosphatase-1 activity. Amantadine also decreases the phosphorylation of threonine-75 consistent with activity as a partial N-methyl-D-aspartate (NMDA) receptor antagonist and partial dopamine agonist. These data demonstrate that targeting the DARPP-32 signaling cascade represents a promising novel therapeutic approach in the treatment of persistent deficits following a TBI.
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Experimental neurology · Jun 2011
Protection against oxaliplatin-induced mechanical hyperalgesia and intraepidermal nerve fiber loss by minocycline.
Treatment with the chemotherapeutic agent oxaliplatin produces a robust painful neuropathy similar to various other neuropathic conditions which result in loss of nerve fibers innervating the skin. This loss of intraepidermal nerve fibers (IENFs) appears to play an important role in neuropathy, but has yet to be investigated in oxaliplatin-induced neuropathic pain. For this study, mechanical hyperalgesia and IENF density were measured in rats receiving oxaliplatin, given at a dosage of 2 mg/kg every other day for four injections. ⋯ Immunohistochemistry using the pan-neuronal marker PGP9.5 was used to investigate IENF densities in hind paw skin on Day 15 and Day 30. The results show that a robust mechanical sensitivity developed in oxaliplatin treated animals, as did a pronounced decrease in epidermal nerve fibers, and these outcomes were effectively prevented by minocycline treatment. This is the first study to show changes in IENF density in oxaliplatin treated animals, and confirm not only a relationship between IENF loss and hypersensitivity but also prevention of both with minocycline treatment.