Neuroscience letters
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Neuroscience letters · Mar 2013
Signal flow and pathways in response to early Wallerian degeneration after rat sciatic nerve injury.
Wallerian degeneration (WD) remains a subject of critical research interest in modern neurobiology. WD is a process which a large number of genes are differentially regulated, especially the early response to activate nerve degeneration and regeneration, but the precise mechanisms remain elusive. ⋯ KEGG pathway analysis revealed activity mainly relating to cytokine-cytokine receptor interaction, MAPK signaling pathway, Jak-STAT signaling pathway, ErbB signaling pathway and TGF-beta signaling pathway involved in the recurrent neural networks that were regulated by the key factors, Cldn-14, Cldn-15, ITG, BID and BIRC3. These results will help to much better understand information relating to the early response to WD and provide us with a firmer basis in future investigations on the molecular mechanisms of WD that regulate nerve degeneration and/or regeneration.
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Neuroscience letters · Mar 2013
Antinociception by systemically-administered acetaminophen (paracetamol) involves spinal serotonin 5-HT7 and adenosine A1 receptors, as well as peripheral adenosine A1 receptors.
Acetaminophen (paracetamol) is a widely used analgesic, but its sites and mechanisms of action remain incompletely understood. Recent studies have separately implicated spinal adenosine A(1) receptors (A(1)Rs) and serotonin 5-HT(7) receptors (5-HT(7)Rs) in the antinociceptive effects of systemically administered acetaminophen. In the present study, we determined whether these two actions are linked by delivering a selective 5-HT(7)R antagonist to the spinal cord of mice and examining nociception using the formalin 2% model. ⋯ DPCPX in normal mice; this was also observed in A(1)R wild type mice, but not in those lacking A(1)Rs. In summary, we demonstrate a link between spinal 5-HT(7)Rs and A(1)Rs in the spinal cord relevant to antinociception by systemic acetaminophen. Furthermore, we implicate peripheral A(1)Rs in the antinociceptive effects of locally- and systemically-administered acetaminophen.
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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
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.