Brain research
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During systemic immune challenge, the organum vasculosum laminae terminalis (OVLT) with its dense vascularization by fenestrated capillaries lacking blood-brain barrier function allows direct access of circulating pyrogens to brain tissue located in close vicinity to the preoptic area. We aimed to analyze direct responses of OVLT cells to exposure to lipopolysaccharide (LPS) and fibroblast-stimulating lipopeptide-1 (FSL-1) or the cytokines tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6. A primary microculture of the OVLT was established from topographically excised rat pup brain tissue, with cellular identification by marker protein-specific immunocytochemistry. ⋯ TNF-α evoked calcium signals in 11% of neurons, 22% of astrocytes, and 5% of microglial cells tested. A considerable population of neurons (11%) but only few astrocytes and microglial cells responded to IL-6, whereas 8% of microglial cells and 3% of astrocytes or neurons were activated by IL-1β. The demonstration of direct cellular responses of OVLT-intrinsic cells to stimulations with LPS or cytokines reinforces the suggested role of this brain structure as a responsive brain site to circulating pyrogens.
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Activation of nucleus factor-kappaB (NF-κB) in the dorsal root ganglia (DRG) is critical for development of neuropathic pain. The underlying mechanisms, however, are largely unknown. In the present work we tested if the activation of NF-κB is required for re-expression of Nav1.3, which is important for development of neuropathic pain, in uninjured DRG neurons. ⋯ As our previous work has shown that up-regulation of tumor necrosis factor-alpha (TNF-α) in DRG is responsible for the re-expression of Nav1.3 in uninjured DRG neurons following L5 ventral root injury, we investigated whether activation of NF-κB is essential for the up-regulation of Nav1.3 by TNF-α. Results showed that application of rat recombinant TNF-α (rrTNF) into the cultured normal adult rat DRG neurons increased the immunoreactive (IR) of Nav1.3 localized mainly around the cell membrane and pre-treatment with PDTC blocked the change dose-dependently. The data suggested that injury to ventral root might lead to neuropathic pain and the re-expression of Nav1.3 in primary sensory neurons by activation of NF-κB.
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Activation of spinal cord microglia and astrocytes after peripheral nerve injury contributes to the development of behavioral hypersensitivity. Suppression of spinal cord glial activation attenuates the development of nerve injury-induced allodynia. The contribution of spinal cord glia to existing allodynia, however, is not known. ⋯ Propentofylline treatment on days 14-21 or 60-67 did not reverse existing allodynia. Propentofylline infusion (10 μg/d) inhibited astrocytic activation bilaterally on days 0-7, 14-21, and 60-67 and inhibited microglial activation on days 14-21 but not on days 0-7 and 60-67. These results suggest that activation of spinal glia, especially astrocytes, dominantly contributes to the development of neuropathic pain and also to mirror-image pain.
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Cerebral vasospasm (CV) is the main complication of spontaneous subarachnoid hemorrhage (SAH), affecting clinical outcome of patients with SAH. Accumulating evidence indicates that apolipoprotein E (apoE protein, APOE gene) gene polymorphism is associated with prognosis of patients with SAH. The current study aimed to investigate the association of promoter polymorphism of APOE with CV in patients with SAH. ⋯ Uni- and multivariate logistic regression analyses also showed that promoter -219T was a risk factor to predispose CV after SAH. However, there was no significant association between promoter -491A/T (rs#449647) or -427C/T (rs#769446) polymorphisms and SAH induced CV (P>0.05). Our finding suggests that patients with APOE -219T promoter are apt to CV after spontaneous SAH.
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Triptans, acting as serotonin, 5-HT(1B/1D/1F), receptor agonists, provide an effective and established treatment option in migraine and cluster headache. Clinical observations suggest a relatively specific effect of these compounds on primary headache disorders, but not in other pain syndromes. The mechanism of this specificity, however, is not well understood. ⋯ There was a good agreement for 5-HT(1B) and 5-HT(1D) receptors to that previously demonstrated in Vg and DRG L(5), while this was the first characterisation for 5-HT(1F) receptor in any of the five regions, as well as for 5-HT(1B) and 5HT(1D) receptors in DRG C(2), C(5) and T(5). In summary, all three 5-HT receptors are equally represented in Vg and the DRGs examined. We conclude that the triptans are theoretically able to bind to receptors at each level of the peripheral neuraxis without any apparent anatomical preference for the head.