Neuroscience
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Paclitaxel is a first-line chemotherapeutic with the major dose-limiting side effect of painful neuropathy. Previous preclinical studies indicate mitochondrial dysfunction and oxidative stress are associated with this disorder; however no direct assessment of reactive oxygen species (ROS) levels and antioxidant enzyme activity in sensory neurons following paclitaxel has been undertaken. As expected, repeated low doses of systemic paclitaxel in rats induced long-lasting pain behaviour with a delayed onset, akin to the clinical scenario. ⋯ In peripheral sensory nerves, CuZnSOD activity was increased at day 7, and at peak pain, MnSOD, CuZnSOD and GPx activity were increased. Catalase activity was unaltered in DRG and saphenous nerves. These data suggest that neuronally-derived mitochondrial ROS, accompanied with an inadequate endogenous antioxidant enzyme response, are contributory factors in paclitaxel-induced painful neuropathy.
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Injury to the recurrent laryngeal nerve (RLN) leads to the loss of ipsilateral laryngeal fold movement, with dysphonia, and occasionally dysphagia. Functional movement of the vocal folds is never restored due to misrouting of regenerating axons to agonist and antagonist laryngeal muscles. Changes of neurotrophic factor expression within denervated muscles occur after nerve injury and may influence nerve regeneration, axon guidance and muscle reinnervation. ⋯ The results suggest that certain neurotrophic factor expression is strongly correlated to the reinnervation pattern of the regenerating RLN. These factors may be involved in guidance and neuromuscular junction formation during nerve regeneration. In the future, their manipulation may enhance the selective reinnervation of the larynx.
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The aim of the present work was to characterize neurons in the archi- and neocortical white matter, and to investigate their distribution in mesial temporal sclerosis. Immunohistochemistry and quantification of neurons were performed on surgically resected tissue sections of patients with therapy-resistant temporal lobe epilepsy. Temporal lobe tissues of patients with tumor but without epilepsy and that from autopsy were used as controls. ⋯ No colocalization of Tbr1 was observed with the inhibitory neuronal markers, calcium-binding proteins. We suggest that a large population of white matter neurons comprises remnants of the subplate. Furthermore, we propose that a subset of white matter neurons was arrested during migration, highlighting the role of cortical maldevelopment in epilepsy associated with mesial temporal sclerosis.
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Somatosensory information from the limbs reaches the contralateral Primary Sensory Cortex (S1) with a delay of 23ms for finger, and 40ms for leg (somatosensory N20/N40). Upon arrival of this input in the cortex, motor evoked potentials (MEPs) elicited by Transcranial Magnetic Stimulation (TMS) are momentarily inhibited. This phenomenon is called 'short latency afferent inhibition (SAI)' and can be used as a tool for investigating sensorimotor interactions in the brain. ⋯ No ipsilateral SAI was detected in the lower limb (TA) at any of the tested ISIs. The delayed onset timing of ipsilateral SAI suggests that transcallosal communication mediates this inhibitory process for the upper limb. The complete absence of ipsilateral SAI in the lower limb warrants consideration of the potential limb-specific differences in demands for bilateral sensorimotor integration.
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In the last decades it has been shown that two components of the event-related potentials (ERPs), the feedback-related negativity (FRN) and the P300, reflect the evaluation of the outcomes of a given course of action. Within the reinforcement learning theory, the prevailing interpretation of the relationship between FRN and P300 is the classical "independent coding model". This model proposes that the FRN is only sensitive to feedback valence whereas the P300 is only sensitive to feedback magnitude. ⋯ Regarding magnitude, this only affects the feedback P300, and only in conjunction with difficulty. Finally, we found that task difficulty has the opposite effect on these components, both in their latencies and discriminability. Our results suggest that the FRN and the feedback-P300 in fact reflect different performance monitoring processes in a flexible way that depends on the behavioral context.