Experimental neurology
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Experimental neurology · Dec 2009
Influence of the vanilloid receptor TRPV1 on the activation of spinal cord glia in mouse models of pain.
Although activation of spinal glia has been implicated in the development of pathological pain, the mechanisms underlying glial activation are not fully understood. One such mechanism may be triggered by reaction to neuroactive substances released from central axons of sensory afferents. ⋯ We found that (i) naïve KO mice had denser immunostaining for both Iba1 and GFAP than naive WT mice; (ii) the immunostaining for Iba1 increased significantly in treated mice, compared to naïve mice, 3 days after capsaicin and 7-14 days after AIA or PSNL, and was significantly greater in WT than in KO mice 3 days after capsaicin, 7-14 days after AIA, and 7 days after PSNL; and iii) the immunostaining for GFAP increased significantly in treated mice, compared to naïve mice, 3 days after capsaicin and 14-21 days after AIA or PSNL, and was significantly greater in WT than in KO mice 14 days after AIA or PSNL. Our results suggest that TRPV1 plays a role in the activation of spinal glia in mice with nociceptive, inflammatory, and neuropathic pain.
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Experimental neurology · Dec 2009
Treatments (12 and 48 h) with systemic and brain-selective hypothermia techniques after permanent focal cerebral ischemia in rat.
Mild hypothermia lessens brain injury when initiated after the onset of global or focal ischemia. The present study sought to determine whether cooling to approximately 33 degrees C provides enduring benefit when initiated 1 h after permanent middle cerebral artery occlusion (pMCAO, via electrocautery) in adult rats and whether protection depends upon treatment duration and cooling technique. In the first experiment, systemic cooling was induced in non-anesthetized rats through a whole-body exposure technique that used fans and water mist. ⋯ A direct and uncomplicated comparison between methods is problematic, however, due to unknown gradients in brain temperature and the use of two separate experiments. In summary, prolonged cooling, even when delayed after onset of pMCAO, provides enduring behavioral and histological protection sufficient to suggest that it will be clinically effective. Nonetheless, further pre-clinical work is needed to improve treatment protocols, such as identifying the optimal depth of cooling, and how these factors interact with cooling method.
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Experimental neurology · Dec 2009
Comparative StudyFlavocoxid counteracts muscle necrosis and improves functional properties in mdx mice: a comparison study with methylprednisolone.
Muscle degeneration in dystrophic muscle is exacerbated by the endogenous inflammatory response and increased oxidative stress. A key role is played by nuclear factor(NF)-kappaB. We showed that NF-kappaB inhibition through compounds with also antioxidant properties has beneficial effects in mdx mice, the murine model of Duchenne muscular dystrophy (DMD), but these drugs are not available for clinical studies. ⋯ NF-kappaB binding activity was investigated by electrophoresis mobility shift assay. The administration of flavocoxid: (1) ameliorated functional properties in vivo and ex vivo; (2) reduced CK; (3) reduced the expression of oxidative stress markers and of inflammatory mediators; (4) inhibited NF-kappaB and mitogen-activated protein kinases (MAPKs) signal pathways; (5) reduced muscle necrosis and enhanced regeneration. Our results highlight the detrimental effects of oxidative stress and NF-kappaB, MAPKs and COX/5-LOX pathways in the dystrophic process and show that flavocoxid is more effective in mdx mice than methylprednisolone.