Neuroscience letters
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Neuroscience letters · Feb 2013
The blockade of NMDA receptor ion channels by ketamine is enhanced in developing rat cortical neurons.
Ketamine is a non-competitive antagonist of NMDA receptors (NMDARs) commonly used as a dissociative anesthetic in many pediatric procedures. Ketamine acts primarily by blocking NMDA ligand-gated channels. Experimental studies indicate that ketamine administration used for inducing clinically relevant anesthesia can lead to neurotoxic effects, such as apoptosis, selectively on immature brain neurons. ⋯ In contrast, the blockade of eEPSCs in mature neurons recovered completely from the inhibition by ketamine in a time-dependent manner. These results indicate that ketamine produces a greater and longer blocking effect on NMDAR channels in immature neurons than in mature neurons. This differential effect is likely to be a critical link to the higher vulnerability to ketamine-induced neurotoxicity in neurons of the developing brain.
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Neuroscience letters · Feb 2013
Contribution of systemic factors in the pathophysiology of repeated blast-induced neurotrauma.
Blast-induced traumatic brain injury is complex and involves multiple factors including systemic pathophysiological factors in addition to direct brain injuries. We hypothesize that systemic activation of platelets/leukocytes plays a major role in the development and exacerbation of brain injury after blast exposure. A mouse model of repeated blast exposure that results in significant neuropathology, neurobehavioral changes and regional specific alterations in various biomolecules in the brain was used for the proposed study. ⋯ Histopathological analysis of the brains of blast exposed mice showed constriction of blood vessels compared to the respective controls, a phenomenon similar to the reported cerebral vasoconstriction in blast affected victims. These results suggest that repeated blast exposure leads to acute activation of platelets/leukocytes which can augment the pathological effects of brain injury. Platelet/leukocyte targeted therapies can be evaluated as potential acute treatment strategies to mitigate blast-induced neurotrauma.
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Neuroscience letters · Feb 2013
Reduced spike frequency adaptation in Purkinje cells of the vestibulocerebellum.
Firing regularity has long been an issue of firing dynamics in the vestibular circuitry. Spike frequency adaption (SFA) is ubiquitous in neuronal activity and can modulate neural coding, which may disrupt the regularity or accuracy of firing. We previously observed different characteristics of intrinsic excitability in Purkinje cells (PCs) of lobule X (vestibulocerebellum) compared to lobules III-V (spinocerebellum). ⋯ The comparison of duration of action potential showed no significant difference between lobules III-V and lobule X PCs during SFA even in low-frequency firing. The lack of SFA in lobule X PCs, as a part of vestibulocerebellum, might be involved in a consistent and regular coordination of vestibular function by the cerebellar cortex in response to low vestibular stimulation. However, the difference of SFA between lobules may be explained by other mechanisms than those which have been reported to be responsible for the SFA formation.
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Neuroscience letters · Feb 2013
Ultra-late EEG potential evoked by preferential activation of unmyelinated tactile afferents in human hairy skin.
Human tactile sensibility in hairy skin is mediated not only by fast conducting myelinated (Aβ) afferents, but also by a system of slow conducting, unmyelinated afferents that respond preferentially to light touch, C-tactile (CT) afferents. This system has previously been shown to correlate with the pleasantness of tactile stimuli, where a soft brush moving at 1-3cm/s activates CT afferents strongly. Functional magnetic resonance imaging (fMRI) studies have shown that preferential CT fiber stimulation activates the posterior insula cortex. ⋯ Furthermore, results from brushing at lower and higher speeds showed that the CT potential was modulated by this stimulation. We conclude that the late potential is consistent with activity in a frontal cortical network following hairy skin peripheral stimulation. This provides an important tool for further studies of the CT fiber system and for clinical examination of peripheral unmyelinated afferents.
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Neuroscience letters · Feb 2013
A selective inhibitor of Drp1, mdivi-1, acts against cerebral ischemia/reperfusion injury via an anti-apoptotic pathway in rats.
Mitochondrial division inhibitor (mdivi-1) is a derivative of quinazolinone that acts as a selective inhibitor of a mitochondrial fission protein Drp1. A previous study demonstrated that as a selective inhibitor of Drp1, mdivi-1 has a protective effect in an experimental model of heart ischemia/reperfusion injury. In this study, we investigated the protective effects of mdivi-1 on cerebral ischemia/reperfusion injury in a middle cerebral artery occlusion mouse model. ⋯ This neuroprotective effect was dose-dependent. Mdivi-1 treatment blocked apoptotic cell death in cerebral ischemia/reperfusion injury, and significantly decreased the expression of Drp1 and Cytochrome C. These results suggest that mdivi-1 exerts neuroprotective effects against nerve injury after cerebral ischemia/reperfusion, and the underlying mechanism may be through the prevention of Cytochrome C release and suppression of the mitochondrial apoptosis pathway.