Experimental neurology
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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 · Apr 2014
The pivotal role played by lipocalin-2 in chronic inflammatory pain.
Lipocalin-2 (LCN2) is an acute phase protein induced in response to injury, infection or other inflammatory stimuli. Based on the previously reported involvement of LCN2 in chemokine induction and in the recruitment of neutrophils at the sites of infection or tissue injury, we investigated the role of LCN2 in the pathogenesis of chronic/persistent inflammatory pain hypersensitivity. In the complete Freund's adjuvant (CFA)-induced chronic inflammatory pain model, LCN2 expression was strongly induced in the ipsilateral hindpaws, peaking at 12h after CFA injection and then gradually subsiding. ⋯ Furthermore, neutrophil infiltration, myeloperoxidase activity, expression of TNF-α, IL-1β and MIP-2 in CFA-injected hindpaws, and spinal glial activation were markedly reduced by Lcn2 deficiency. An intraplantar injection of recombinant LCN2 protein induced thermal and mechanical hypersensitivities in naïve mice, and this was accompanied by neutrophil and macrophage infiltration into the hindpaws and glial activation in the dorsal horn of the spinal cord. Taken together, our results show that inflammatory cell-derived LCN2 at the sites of inflammation plays important roles in central sensitization and the subsequent nociceptive behavior in the rodent model of chronic inflammatory pain.
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Experimental neurology · Mar 2014
Paclitaxel alters the evoked release of calcitonin gene-related peptide from rat sensory neurons in culture.
Peripheral neuropathy (PN) is a debilitating and dose-limiting side effect of treatment with the chemotherapeutic agent, paclitaxel. Understanding the effects of paclitaxel on sensory neuronal function and the signaling pathways which mediate these paclitaxel-induced changes in function are critical for the development of therapies to prevent or alleviate the PN. The effects of long-term administration of paclitaxel on the function of sensory neurons grown in culture, using the release of the neuropeptide calcitonin gene-related peptide (CGRP) as an endpoint of sensory neuronal function, were examined. ⋯ When neurons were stimulated with capsaicin or AITC, a low concentration of paclitaxel (10nM) augmented transmitter release, whereas a high concentration (300 nM) reduced transmitter release in a time-dependent manner; however, when high extracellular potassium was used as the evoking stimulus, all concentrations of paclitaxel augmented CGRP release from sensory neurons. These results suggest that paclitaxel alters the function of sensory neurons in vitro, and suggest that the mechanisms by which paclitaxel alters neuronal function may include functional changes in TRP channel activity. The described in vitro model will facilitate future studies to identify the signaling pathways by which paclitaxel alters neuronal sensitivity.
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Non-dystrophic myotonias are rare diseases caused by mutations in skeletal muscle chloride and sodium ion channels with considerable phenotypic overlap between diseases. Common symptoms include muscle stiffness, transitory weakness, fatigue, and pain. Although seldom life-shortening, these myotonias cause life-time disability and affected individuals cannot perform many daily activities. ⋯ A recent study published in Experimental Neurology (Desaphy et al., 2013) explored this question further by comparing the biophysical properties of 3 chloride channel mutations associated with recessive myotonia congenita, with varying susceptibility to transient weakness. The authors identified a variety of functional defects in channel behavior among the 3 mutations, suggesting that this variability contributes to the differing phenotypes among chloride channelopathies. This commentary discusses nondystrophic myotonias, the results of Desaphy et al., and the treatment challenges in this rare disease.
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Experimental neurology · Mar 2014
Spreading depression triggers ictaform activity in partially disinhibited neuronal tissues.
There is unequivocal electrophysiological evidence that spreading depression (SD) can trigger epileptiform field potentials. In vitro experiments on human brain tissues indicated that γ-aminobutyric acid (GABA)-mediated inhibition prevented this process. Intra- and extracellular recordings of bioelectrical activities were performed in the rodent neocortex, hippocampus and amygdala after perfusion of low concentrations of the GABAA antagonist bicuculline and induction of SD by KCl application. ⋯ Changes of characteristic features of APs occurred after SD persisted during the appearance of epileptiform activities. These results indicate that SD increases neuronal excitability and facilitates synchronization of neuronal discharges in the presence of partial disinhibition of neuronal tissues. Our findings might explain the occurrence of seizures in neurological disorders with partial impairment of inhibitory tone, such as brain ischemia and epilepsy.