Neuroscience letters
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Neuroscience letters · Sep 2013
Systemic diphenidol reduces neuropathic allodynia and TNF-alpha overexpression in rats after chronic constriction injury.
Diphenidol has been shown to block voltage-gated Na(+) channels, which are associated with specific types of pain. Here, we evaluated the effects of diphenidol on chronic constriction injury (CCI)-evoked allodynia and expression of tumor necrosis factor-α (TNF-α). A peripheral nerve injury was elicited in rats by placing four loosely constrictive ligatures around the sciatic nerve. ⋯ Both diphenidol 2 and 10 μmol/kg groups, but not 0.4 μmol/kg diphenidol, displayed lower TNF-α level in the sciatic nerve than the CCI group (P<0.05) on day 7 after CCI. Our results support the conclusion that systemic diphenidol produced a dose-related inhibition of mechanical allodynia following chronic constriction injury of the sciatic nerve. This antiallodynic effect is related to the decrease of TNF-α expression in the sciatic nerve of CCI rats.
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Both TRPV1 and TRPA1 are non-selective cation channels. They are co-expressed, and interact in sensory neurons such as dorsal root ganglia (DRG) and trigeminal ganglia (TG), and are involved in nociception, being activated by nociceptive stimuli. Immunohistological localization of TRPV1 in vestibular ganglion (VG) neurons has been reported. ⋯ Moreover, in some VG neurons, a [Ca(2+)]i increase was evoked by both capsaicin and cinnamaldehyde in the same neuron. In summary, our histological and physiological studies reveal that TRPV1 and TRPA1 are expressed in VG neurons. It is suggested that TRPV1 and TRPA1 in VG neurons might participate in vestibular function and/or dysfunction such as vertigo.
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Neuroscience letters · Sep 2013
Distinct patterns of expression of traumatic brain injury biomarkers after blast exposure: role of compromised cell membrane integrity.
Glial fibrillary acidic protein (GFAP), a protein enriched in astrocytes, and Tau, a protein abundant in neuronal microtubules, are being widely studied as biomarkers of brain injury, and persistent severity-dependent increases in brain and blood have been reported. Studies on the acute changes of these proteins after blast exposure are limited. Using a mouse model of closely-coupled repeated blast exposures, we have evaluated acute changes in the levels of GFAP and total Tau by Western blotting. ⋯ Liver and spleen tissue showed significant increases in the levels of GFAP and Tau protein at 6 and 24 h post-blast exposures whereas semi-quantitative RT-PCR analysis of liver showed no significant changes in the levels of GFAP or Tau mRNAs. These results suggest that blast exposure causes transient changes in cell membrane integrity in multiple organs leading to abnormal migration of proteins from the tissues to the plasma and vice versa. This transient changes in cell membrane permeability and subsequent bidirectional movement of molecules may contribute to the pathophysiology of TBI and polytrauma after blast exposure.
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Neuroscience letters · Sep 2013
NKCC1 and KCC2 protein expression is sexually dimorphic in the hippocampus and entorhinal cortex of neonatal rats.
Seizure susceptibility appears to be greater in males than females during the early developmental stages of the brain when the gamma-aminobutyric acid (GABA), acting through its GABA-A receptor, predominantly produces neuronal depolarization. GABA-mediated excitation has been observed when the NKCC1 (chloride importer) expression level is higher than KCC2 (chloride exporter). ⋯ In males, the NKCC1/β-actin expression ratio was constant during the first week, peaking almost three-fold higher than the initial level at PND9 in the hippocampus and at PND11 in the entorhinal cortex and then returning to the initial values at PND13, whereas the KCC2/β-actin expression ratio increased gradually to reach a maximal and steady level at PND5, which were nearly two- and four-fold higher in the hippocampus and entorhinal cortex, respectively, compared with the intial level. In conclusion, the NKCC1/β-actin and KCC2/β-actin expression ratios displayed a specific expression profile for each gender and cerebral region, which could be related with the differences in seizure susceptibility observed between genders.
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Neuroscience letters · Sep 2013
CB1 cannabinoid receptor agonist prevents NGF-induced sensitization of TRPV1 in sensory neurons.
The transient receptor potential vanilloid type 1 channel (TRPV1) and nerve growth factor (NGF) are important mediators of inflammatory pain. NGF released during inflammation sensitizes TRPV1 in afferent nerve endings of peripheral nociceptors, increasing pain sensation. Cannabinoids, by activating CB1 G protein-coupled receptors, produce analgesia in a variety of pain models, though the exact mechanisms are not known. ⋯ Neither this rate, nor the magnitude of the sensitization (198 ± 63% of baseline) were different from that seen in cells not treated with NGF (3 of 25 cells sensitized (12.0%), 253 ± 70% of baseline). Pretreatment with the CB1 antagonist AM-251 (100 nM) prevented the effect of ACEA on NGF-induced sensitization. These results support the hypothesis that cannabinoids, acting through CB1 receptors, may produce analgesia in part by preventing NGF-induced sensitization of TRPV1 in afferent nociceptor nerve endings.