Neuroscience
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Inosine (hypoxanthine 9-beta-D-ribofuranoside), a purine nucleoside with multiple intracellular roles, also serves as an extracellular modulatory signal. On neurons, it can produce anti-inflammatory and trophic effects that confer protection against toxic influences in vivo and in vitro. The protective effects of inosine treatment might also be mediated by its metabolite urate. ⋯ Urate concentration was not significantly increased by inosine treatment however there was a significant increase in levels of other purine metabolites, such as adenosine, hypoxanthine and xanthine. In particular, in MES 23.5-astrocytes co-cultures, inosine medium content was reduced by 99% and hypoxanthine increased by 127-fold. Taken together these data raise the possibility that inosine might have a protective effect in PD that is independent of any effects mediated through its metabolite urate.
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Spinal microglia are widely recognized as activated by and contributing to the generation and maintenance of inflammatory and nerve injury related chronic pain; whereas the role of spinal astrocytes has received much less attention, despite being the first glial cells identified as activated following peripheral nerve injury. Recently it was suggested that microglia do not appear to play a significant role in chemotherapy-induced peripheral neuropathy (CIPN), but in contrast astrocytes appear to have a key role. In spite of the generalizability of astrocyte recruitment across chemotherapy drugs, its correlation to the onset of the behavioral CIPN phenotype has not been determined. ⋯ Microglia were strongly activated following SNL, but not activated at any of the time points observed following chemotherapy treatments. Astrocytes were activated following both oxaliplatin and bortezomib treatment in a manner that paralleled chemotherapy-evoked behavioral changes. Both the behavioral phenotype and activation of astrocytes were prevented by co-administration of minocycline hydrochloride in both CIPN models, suggesting a common mechanism.
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Targeting cortical neuroplasticity through rehabilitation-based practice is believed to enhance functional recovery after spinal cord injury (SCI). While prehensile performance is severely disturbed after C6-C7 SCI, subjects with tetraplegia can learn a compensatory passive prehension using the tenodesis effect. During tenodesis, an active wrist extension triggers a passive flexion of the fingers allowing grasping. ⋯ Cortical recruitment became similar to that in HP. Behavioral analysis evidenced decreased movement variability suggesting motor learning of tenodesis. Data suggest that MI training participated to reverse compensatory neuroplasticity in SCI participants, and promoted the integration of new upper limb prehensile coordination in the neural networks functionally dedicated to the control of healthy prehension before injury.
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Animal models of diabetes do not reach the severity of human diabetic neuropathy but relatively mild neurophysiological deficits and minor morphometric changes. The lack of degenerative neuropathy in diabetic rodent models seems to be a consequence of the shorter length of the axons or the shorter animal life span. Diabetes-induced demyelination needs many weeks or even months before it can be evident by morphometrical analysis. ⋯ Morphometrical analysis of the tibial nerve demonstrated a decrease in the number of myelinated fibers, fiber size and myelin thickness at both time-points studied. Moreover, aldose reductase and poly(ADP-ribose) polymerase activities were increased even if the amount of the enzyme was not affected. Thus, type 1 diabetes in newborn mice induces early peripheral neuropathy and may be a good model to assay pharmacological or gene therapy strategies to treat diabetic neuropathy.
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Organization of the central visual pathway is generally studied from a perspective of feedforward processes. However, there are horizontal connections and also strong feedback from extra striate to visual cortex. Here, we use visual stimuli designed to maximize relative differential involvements of these three main types of connections. ⋯ Therefore, surround information beyond the CRF is initially processed by fast connections which we consider to be feedback, whereas spatially tuned mechanisms are relatively slow and presumably mediated by horizontal connections. Overall, results suggest that convergent fast (feedforward) inputs determine size and structure of the CRFs of recipient cells in visual cortex. And fast connections from extra striate regions (feedback) plus slow-tuned connections (horizontal) within visual cortex contribute to spatial influences of CRF surround activation.