Neurotoxicology
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Epidural injection of cyclooxygenase-2 inhibitors has been suggested as a useful therapeutic modality in pain management in animal studies and clinical settings. Direct epidural administration of parecoxib, a highly selective cyclooxygenase-2 inhibitor, may have advantages over its parenteral administration regarding required dose, side effects, and efficacy. However, no animal studies have been performed to investigate the possible neurotoxicity of epidurally injected parecoxib. ⋯ Histological examination showed no evidence suggestive of neuronal body or axonal lesions, gliosis, or myelin sheet damage in group N or P at any time. However, all rats in group E showed sensory-motor dysfunction, behavioral change, or histopathological abnormalities. No neurotoxicity on the spinal cord or abnormalities in sensorimotor function or behavior was noted in rats that received epidural parecoxib.
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Methylmercury (MeHg) is a widespread environmental toxicant with major actions on the central nervous system. Among the neurons reportedly affected in cases of Hg poisoning are motor neurons; however, the direct cellular effects of MeHg on motor neurons have not been reported. Ratiometric fluorescence imaging, using the Ca(2+)-sensitive fluorophore fura-2, was used to examine the effect of MeHg on Ca(2+) homeostasis in primary cultures of mouse spinal motor neurons. ⋯ The voltage-dependent Na(+) channel blocker tetrodotoxin (TTX, 1 μM) did not alter the MeHg-induced increases in fura-2 fluorescence ratio. Thus, MeHg alters Ca(2+) homeostasis in mouse spinal motor neurons through excitatory amino acid receptor-mediated pathways, and nifedipine and ω-conotoxin-GVIA-sensitive pathways. Spinal motor neurons are highly sensitive to this effect of acute exposure to MeHg.
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We report the case of a cocaine abuser who presented two consecutive episodes of acute leukoencephalopathy, documented by serial MRI, with favourable outcome. Clinical findings and brain imaging led to the diagnosis of cocaine-induced toxic leukoencephalopathy and other possible mimickers have been excluded on the basis of clinical assessment. ⋯ Of note, case presented in the peculiar form of recurrent episodes of acute leukoencephalopathy, with favourable outcome, which, to our knowledge, has not been described yet. We speculate about the aetiology of this condition, which is still poorly understood.
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Comparative Study
Enhancement of axonal potassium conductance reduces nerve hyperexcitability in an in vitro model of oxaliplatin-induced acute neuropathy.
Oxaliplatin is used in the chemotherapeutic treatment of malignant tumours. A common side effect of oxaliplatin is an acute peripheral neuropathy characterized by axonal hyperexcitability, which can be painful and is aggravated by exposure to cold. Electrophysiological studies on isolated segments of peripheral rodent nerve have been able to replicate oxaliplatin's effect on axonal hyperexcitability in vitro. ⋯ Application of flupirtine (10μM) reduced both the magnitude and duration of oxaliplatin-induced axonal after-activity in myelinated axons. These findings were also confirmed in isolated human sural nerve segments. The data indicate that activation of slow potassium channels in the A-fibres of peripheral nerve may attenuate the acute neuropathy associated with oxaliplatin in humans.
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Comparative Study
Mechanism study of Aconitum-induced neurotoxicity in PC12 cells: involvement of dopamine release and oxidative damage.
The Aconitum has been widely used as an important component in traditional Chinese medicine. However, it can cause neurotoxicity, and the mechanism has not been fully elucidated. The present study aimed to investigate the potential dopaminergic neurotoxicity of Aconitum and its mechanism. ⋯ Moreover, PC12 cells proliferation was inhibited and apoptotic death was detected after Aconitum treatment, but this effect could be attenuated by antioxidants. These findings suggest that Aconitum can damage PC12 cells through oxidative stress mechanism. In conclusion, our results indicate that Aconitum can evoke dopamine release from dopaminergic neurons; excessive extracellular of dopamine can then create stresses on cellular antioxidant systems and induce neuron apoptosis.