Neuroscience
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Reactive oxygen species (ROS) are major exacerbation factor in acute ischemic stroke, and thrombolytic agent tissue plasminogen activator (tPA) may worsen motor function and cerebral infarcts. The platinum nanoparticle (nPt) is a novel ROS scavenger, and thus we examined the clinical and neuroprotective effects of nPt in ischemic mouse brains. Mice were subjected to transient middle cerebral artery occlusion (tMCAO) for 60 min and divided into the following four groups by intravenous administration upon reperfusion, vehicle, tPA, tPA+nPt, and nPt. ⋯ All these results became pronounced with tPA administration, and were greatly reduced by nPt. The present study demonstrates that nPt treatment ameliorates neurological function and brain damage in acute cerebral infarction with neuroprotective effect on NVU and inactivation of MMP-9. The strong reduction of ROS production by nPt could account for these remarkable neurological and neuroprotective effects against ischemic stroke.
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The spontaneously epileptic rat (SER) is a double mutant (zi/zi, tm/tm) which begins to exhibit tonic convulsions and absence seizures after 6 weeks of age, and repetitive tonic seizures over time induce sclerosis-like changes in SER hippocampus with high brain-derived neurotrophic factor (BDNF) expression. Levetiracetam, which binds to synaptic vesicle protein 2A (SV2A), inhibited both tonic convulsions and absence seizures in SERs. We studied SER brains histologically and immunohistochemically after verification by electroencephalography (EEG), as SERs exhibit seizure-related alterations in the cerebral cortex and hippocampus. ⋯ The extent of low SV2A expression/distribution in SERs was particularly remarkable in the frontal (51% of control) and entorhinal cortices (47%). Lower synaptotagmin-1 expression (vs Wistar rats) was located in the frontal (31%), piriform (13%) and entorhinal (39%) cortices, and IML of the DG (38%) in SER. Focal low distribution of synaptotagmin-1 accompanying low SV2A expression may contribute to epileptogenesis and seizure propagation in SER.
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The caudal division of the trigeminal spinal nucleus (Sp5C) is an important brainstem relay station of orofacial pain transmission. The aim of the present study was to examine the effect of cortical electrical stimulation on nociceptive responses in Sp5C neurons. Extracellular recordings were performed in the Sp5C nucleus by tungsten microelectrodes in urethane-anesthetized Sprague-Dawley rats. ⋯ Inhibitory cortical effects were mediated by the activation of GABAergic and glycinergic neurons because they were blocked by bicuculline or strychnine. The S1 and S2 cortical stimulation also inhibited Sp5C neurons in animals with constriction of the infraorbital nerve. Consequently, the corticofugal projection from S1 and S2 cortical areas modulates nociceptive responses of Sp5C neurons and may control the transmission of nociceptive sensory stimulus.
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Thrombolysis with tissue plasminogen activator (tPA) is the only FDA-approved therapy for acute ischemic stroke. However, hemorrhagic transformation, neurotoxicity, and a short treatment time window comprise major limitations for thrombolytic therapy. The purpose of the present study was to investigate whether fasudil, a Rho kinase (ROCK) inhibitor, would prevent tPA-associated hemorrhagic transformation and extend the reperfusion window in an experimental stroke model in mice. ⋯ These changes significantly reduced mortality and increased locomotor activity at 7 days after the reperfusion. Furthermore, the administration of both drugs prevented injury to the human brain endothelial cells via the reduction of matrix metalloproteinase-9 (MMP-9) activity. These findings indicate that fasudil prevents the hemorrhagic transformation induced by focal cerebral ischemia in mice treated with tPA, at least in part, by inhibiting the increased activity of MMP-9 in endothelial cells.
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Randomized Controlled Trial
Influence of the amount of use on hand motor cortex representation: effects of immobilization and motor training.
Converging evidence from animal and human studies has revealed that increased or decreased use of an extremity can lead to changes in cortical representation of the involved muscles. However, opposite experimental manipulations such as immobilization and motor training have sometimes been associated with similar cortical changes. Therefore, the behavioral relevance of these changes remains unclear. ⋯ No change was found for other TMS variables (motor thresholds or map location/volume/area) in either condition. In conclusion, our results indicate that a 4-day decrease, but not increase, in the amount of use of nondominant hand muscles is sufficient to induce a change in corticospinal excitability. The lack of a training effect might be explained by the use of an unspecific task (that is nevertheless representative of "real-life" training situations) and/or by insufficient duration/intensity to induce long-lasting changes.