Brain research
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The developmental pattern of sodium channel expression in neurons of primary sensory ganglia is likely reflected in the electrical behavior of these cells. Little information is available on how voltage-gated sodium channels in sensory neurons are expressed during development in the trigeminal-innervated craniofacial region, where sensitivity is fundamental during early stages of life. Using in situ hybridization, we here demonstrate a differential both regional and transcript-dependent distribution of sodium channel alpha- and beta-subunits between Embryonic day (E)15 and Postnatal day (P)5/6 in the rat trigeminal ganglion. ⋯ In the ophthalmic TG portion, there was a higher expression level of Na(v)1.8 and Na(v)1.9 between E19 and P5/P6 as compared to the maxillary/mandibular part, indicating an unexpected positional difference in channel distribution. mRNA levels of p11, which facilitates the expression of Na(v)1.8, were high at all stages. These findings show that trigeminal ganglion sodium channel transcripts mature in steps that are specific for each transcript. They also raise the possibility that different facial regions could differ in the ability to transmit sensory signals during early life.
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Distal limb pain in diabetes mellitus is frequently attributed to hyperexcitability of primary afferents associated with peripheral neuropathy. However, prior studies have demonstrated that, after traumatic nerve injury, hyperexcitability develops not only within primary afferents but also within pain-signalling neurons of the spinal cord dorsal horn and thalamic ventral posterolateral (VPL) nucleus, establishing a basis for tiered central pain generators or amplifiers. In this study we asked whether hyperexcitability develops within thalamic neurons in experimental painful diabetes. ⋯ Our analysis shows that, in this model of diabetic neuropathic pain, thalamic VPL neurons develop hyperexcitability, with increased responses to phasic brush, press, and pinch stimuli applied to identified peripheral receptive fields. VPL neurons from diabetic rats also display enhanced spontaneous activity, independent of ascending afferent barrage, and enlarged receptive fields. These results suggest that aberrant levels of spontaneous activity and hyper-responsiveness of VPL thalamic neurons may contribute to diabetic neuropathic pain.
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The present study assessed the role of matrix metalloproteinase-2 (MMP-2) and -9 in synapse loss after traumatic brain injury (TBI) and the role of hypoxia inducible factor-1alpha (HIF-1alpha), a transcription factor up-regulated during hypoxia, in the regulation of MMP-2 and -9 expression post-TBI. Adult male Sprague-Dawley rats (n=6 per group, 400 g-425 g) were injured using Marmarou's closed-head acceleration impact model and allowed to survive for 1, 4, 24 and 48 h. In another set of experiments, 30 min after TBI, animals were treated with Minocycline (inhibitor of MMPs), or 2-Methoxyestradiol (2ME2, inhibitor of HIF-1alpha) and sacrificed at 4 h after injury. ⋯ Inhibition of HIF-1alpha reduced expression of MMP-2 and -9. This study showed an early detection of a correlation between synaptic loss and MMP expression after TBI. The data also supports a role for HIF-1alpha in the MMP regulatory cascade in synapse loss after TBI, suggesting potential targets for reducing loss of synaptic terminals.