Experimental neurology
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Experimental neurology · Sep 2013
Alternative splicing of AMPA receptor subunits in the 6-OHDA-lesioned rat model of Parkinson's disease and L-DOPA-induced dyskinesia.
Abnormal corticostriatal plasticity is a key mechanism of L-DOPA-induced dyskinesia (LID) in Parkinson's disease (PD). Antagonists at glutamatergic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, such as IEM 1460, reduce induction and expression of dyskinesia in rat and non-human primate models of PD. AMPA receptor function is regulated by post-transcriptional splicing of subunit mRNA to produce flip and flop isoforms, which may therefore influence corticostriatal plasticity. ⋯ There were no changes in expression of flop isoforms. Alternative splicing of AMPAR subunits contributes to abnormal striatal plasticity in the induction and expression of LID. Increases in GluR2-flip expression depend on activation of Ca(2+)-permeable AMPA receptors, which are a potential target of anti-dyskinetic therapies.
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Over the past 70years, diffuse axonal injury (DAI) has emerged as one of the most common and important pathological features of traumatic brain injury (TBI). Axons in the white matter appear to be especially vulnerable to injury due to the mechanical loading of the brain during TBI. As such, DAI has been found in all severities of TBI and may represent a key pathologic substrate of mild TBI (concussion). ⋯ In addition, recent evidence suggests that TBI may induce long-term neurodegenerative processes, such as insidiously progressive axonal pathology. Indeed, axonal degeneration has been found to continue even years after injury in humans, and appears to play a role in the development of Alzheimer's disease-like pathological changes. Here we review the current understanding of DAI as a uniquely mechanical injury, its histopathological identification, and its acute and chronic pathogenesis following TBI.
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Experimental neurology · Jul 2013
ReviewAdaptive deep brain stimulation (aDBS) controlled by local field potential oscillations.
Despite their proven efficacy in treating neurological disorders, especially Parkinson's disease, deep brain stimulation (DBS) systems could be further optimized to maximize treatment benefits. In particular, because current open-loop DBS strategies based on fixed stimulation settings leave the typical parkinsonian motor fluctuations and rapid symptom variations partly uncontrolled, research has for several years focused on developing novel "closed-loop" or "adaptive" DBS (aDBS) systems. aDBS consists of a simple closed-loop model designed to measure and analyze a control variable reflecting the patient's clinical condition to elaborate new stimulation settings and send them to an "intelligent" implanted stimulator. The major problem in developing an aDBS system is choosing the ideal control variable for feedback. Here we review current evidence on the advantages of neurosignal-controlled aDBS that uses local field potentials (LFPs) as a control variable, and describe the technology already available to create new aDBS systems, and the potential benefits of aDBS for patients with Parkinson's disease.
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Experimental neurology · Jul 2013
Spatial extent of β oscillatory activity in and between the subthalamic nucleus and substantia nigra pars reticulata of Parkinson's disease patients.
Parkinson's disease (PD) is accompanied by a significant amount of β-band (11 Hz-30 Hz) neuronal and local field potential (LFP) oscillatory activity in the subthalamic nucleus (STN). Previous studies have shown significant coherence between neuronal firing and LFPs at β frequencies at sites separated by ~1 mm and that the magnitude of β oscillatory LFP activity and coherence are greatly reduced following levodopa administration. However, these data have been collected from large DBS contact electrodes or pairs of microelectrodes in proximity to each other and so it is not clear whether all regions of STN are synchronized. ⋯ We confirmed previous reports of a progressive attenuation in β power as electrodes were driven from dorsal to ventral STN and into SNr. Furthermore, we found significant β-LFP coherence across the dorsoventral extent of STN. Detailed analysis suggested that at least some of the ventral STN and SNr beta activity was locally generated rather than arising from volume conduction from dorsal STN and thus suggests that β oscillations synchronize both the input and output nuclei of the basal ganglia.
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There is increased interest in neurostimulation as a treatment for drug-resistant epilepsy. Two large pivotal trials have recently been completed, one using bilateral anterior thalamic stimulation and another employing closed loop responsive therapy of the brain. These are potential additions to the therapeutic options for neurostimulation in addition to already approved vagus nerve stimulation. This review will address the principles of the various types of neurostimulation, the results of the pivotal trials and the important considerations for interpreting the results of these trials which differ from trials of antiepileptic drugs.