Neurotoxicity research
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Neurotoxicity research · Apr 2006
Clinical TrialLong term effects of intra-articular botulinum toxin A for refractory joint pain.
The purpose of this case series review is to describe our 12 month clinical experience with intra-articular injections of Botulinum toxin Type A (BoNT/A) for refractory joint pain. Eleven patients with chronic arthritis who had failed treatment with oral and/or intra-articular medications and were not surgical candidates were referred to us for management of moderate to severe refractory joint pain in 15 joints. The use of BoNT/A to treat joint pain is a non-FDA approved "off label" treatment with potential side effects. After a detailed explanation of the joint injection procedure, signed informed consent was obtained for the procedure. Fifteen joints were injected with BoNT/A (Allergan, Inc): six lower extremity joints (3 knees, 3 ankles) with 25-50 units and nine shoulders with 50-100 units. Patients were followed for one year or longer. Maximum relief of pain was measured by comparing baseline pain on a numeric rating scale (0-10) to pain at the time of maximum relief (paired t-test). Maximum improvement in function was assessed using paired t-tests for improvement in active flexion and abduction for the shoulder joint, and by the time to perform sit to stand ten times (the timed stands test, TST) for the lower extremity joints. ⋯ This is the first report of the long term effects of intra-articular BoNT/A injections to treat chronic joint pain and the efficacy of repeated injections. Although this study was small, and uncontrolled the results suggest that IA-BoNT/A injections are an effective and safe treatment for chronic joint pain disorders.
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Neurotoxicity research · Nov 2005
Comparative StudyPro- and anti-inflammatory cytokines regulate the ERK pathway: implication of the timing for the activation of microglial cells.
Pro-inflammatory molecules induce glial activation and the release of potentially detrimental factors capable of generating oxidative damage, such as nitric oxide (NO) and superoxide anion (O2.-). Activated glial cells (astrocytes and microglia) are associated to the inflammatory process in neurodegenerative diseases. A strong inflammatory response could escape endogenous control becoming toxic to neurons and contributing to the course of the disease. ⋯ However, the effect of IL-1beta was observed at 30 min and that of TGF-beta1 only after 24 h of exposure. We propose that acting with different timing, TGF-beta1 and IL-1beta can modulate the extracellular signal-regulated kinase ERK1,2, as a common element for different transduction pathways, regulating the amplitude and duration of glial activation in response to LPS+IFN-gamma. Cross-talk among brain cells may be key for the understanding of inflammatory mechanisms involved in pathogenesis of neurodegenerative diseases.
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A conditioned stimulus (CS) associated with a fearsome unconditioned stimulus (US) generates learned fear. Acquired fear is at the root of a variety of mental disorders, among which phobias, generalized anxiety, the posttraumatic stress disorder (PTSD) and some forms of depression. The simplest way to inhibit learned fear is to extinguish it, which is usually done by repeatedly presenting the CS alone, so that a new association, CS-"no US", will eventually overcome the previously acquired CS-US association. ⋯ In fact, our findings indicate that the reconsolidation hypothesis is essentially incorrect, at least for the form of contextual fear most commonly studied in rodents. Therefore, it seems safe to continue using extinction-based forms of therapy for disorders secondary to acquired fear. Further, it is useful and desirable to device procedures by which the "no US" component of the extinction is strengthened in order to alleviate the symptoms of victims of acquired fear.
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Neurotoxicity research · Jan 2003
Down regulation of sodium channel Na(v)1.1 expression by veratridine and its reversal by a novel sodium channel blocker, RS100642, in primary neuronal cultures.
This study investigated the effects of veratridine-induced neuronal toxicity on sodium channel gene (NaCh) expression in primary forebrain cultures enriched in neurons, and its reversal by a novel sodium channel blocker, RS100642. Using quantitative RT-PCR, our findings demonstrated the expression ratio of NaCh genes in normal fetal rat forebrain neurons to be Na(v)1.2 > Na(v)1.3 > Na(v)1.8 > Na(v)1.1 > Na(v)1.7 (rBII > rBIII > PN3 > rBI > PN1). ⋯ However, treatment of neurons with RS100642 (200 micro M) reversed the down-regulation of the Na(v)1.1 gene expression caused by veratridine. Our findings document for the first time quantitative and relative changes in the expression of various NaCh genes in neurons following injury produced by selective activation of voltage-gated sodium channels, and suggest that the Na(v)1.1 sodium channel gene may play a key role in the neuronal injury/recovery process.
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Neurotoxicity research · Jan 2003
Hyperactivity following postnatal NMDA antagonist treatment: reversal by D-amphetamine.
Three experiments were performed to study the effects of neonatal administration of glutamate receptor antagonists, on either Day 11 (dizocilpine = MK-801, 3 x 0.5 mg/kg, s.c., injected at 0800, 1600 and 2400 h) or Day 10 (Ketamine, 1 x 50 mg/kg, s.c., or Ethanol-Low, 1 x 2.5 mg/kg, or, Ethanol-High, 2 x 2.5 mg/kg, s.c., with 2-h interval) to male mice pups, on spontaneous motor behavior, habituation to a novel situation and D-amphetamine-induced activity in the adult animals. Mice administered MK-801 showed initial hypoactivity followed by hyperactivity over the later (20-40 and 40-60 min) periods of testing. Mice administered Ketamine and Ethanol-High similarly displayed an initial hypoactivity followed by hyperactivity over the later time (20-60 min) of testing. ⋯ Fluoro-jade staining per mm(2) regional brain tissue of MK-801 mice pups expressed as percent of vehicle mice pups showed also that the extensiveness of staining was markedly greater in the parietal cortex, hippocampus, frontal cortex, and lesser so in the laterodorsal thalamus. Ketamine-treated mice showed cell degeneration mainly in the parietal cortex, whereas the Ethanol-High mice showed marked cell degeneration in both the parietal and laterodorsal cortex. The present findings that encompass a pattern of regional neuronal degeneration, disruptions of spontaneous motor activity, habituation deficits and reversal of hyperactivity by a low dose of D-amphetamine suggest a model of Attention Deficit Hyperactivity Disorder that underlines the intimate role of N-methyl-D-aspartate (NMDA) receptors in the developing brain.