Brain research
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A large body of evidence indicates that the hormone erythropoietin (EPO) exerts beneficial effects in the central nervous system (CNS). To date, EPO's effect has been assessed in several experimental models of brain and spinal cord injury. This study was conducted to validate whether treatment with recombinant human EPO (rHuEPO) would limit the extent of injury following experimental TBI. ⋯ BBB breakdown was significantly lower in EPO-treated group than in the placebo-treated group (66.2+/-18.7 mug/g versus 181.3+/-21 mug/g, respectively, P<0.05). EPO treatment reduced injury volume significantly compared with placebo group (17.4+/-5.4 mm3 versus 37.1+/-5.3 mm3, P<0.05). EPO, administered in its recombinant form, affords significant neuroprotection in experimental TBI model and may hold promise for future clinical applications.
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Comparative Study
Chemical and mechanical nerve root insults induce differential behavioral sensitivity and glial activation that are enhanced in combination.
Both chemical irritation and mechanical compression affect radicular pain from disc herniation. However, relative effects of these insults on pain symptoms are unclear. This study investigated chemical and mechanical contributions for painful cervical nerve root injury. ⋯ By day 7 after the combined injury, there were significant (p<0.003) bilateral increases in OX-42 staining over normal. Spinal astrocytic and microglial reactivity follow different patterns after chemical root irritation, compression, and a combined insult. The combination of transient compression and chemical irritation produces sustained bilateral hypersensitivity, sustained ipsilateral spinal astrocytic activation and late onset bilateral spinal microglial activation.
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Major problem involved in treatment of chronic pain with morphine is the development of tolerance and dependence. Previous studies have demonstrated the participation of melanocortin (MC) system in the development of tolerance to antinociceptive effect of morphine. However, the impact of supraspinal MC4 receptors (MC4 R) modulation on this phenomenon and morphine withdrawal hyperalgesia remained unexplored. ⋯ Furthermore, acute treatment with HS014 (0.008 and 0.04 ng/rat, icv) dose dependently attenuated the withdrawal hyperalgesia. This suggests the involvement of central MC4 R in the mechanism of development of tolerance and dependence following chronic morphine administration. We speculate that targeting this receptor may be a novel strategy to improve the effectiveness of morphine in the treatment of chronic pain.
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There are no effective treatments for intracerebral hemorrhage (ICH). Although inflammation is a potential therapeutic target, there is a dearth of information about time-dependent and cell-specific changes in the expression of inflammation-related genes. Using the collagenase-induced ICH model in rats and real-time quantitative RT-PCR we monitored mRNA levels of markers of glial activation, pro- and anti-inflammatory cytokines, enzymes responsible for cytokine activation and several matrix metalloproteases at 6 h and 1, 3 and 7 days after ICH onset. ⋯ Included is the first demonstration that astrocytes are an important source of interleukin-1beta (IL-1beta), interleukin-1 receptor antagonist (IL-1ra), interleukin-6 (IL-6) and MMP-12. Importantly, our results demonstrate that while delayed minocycline treatment effectively reduces early up-regulation of TNFalpha and MMP-12, its efficacy is lost when treatment is extended for up to a week, and it does not reduce several other genes associated with microglia activation. These results suggest caution in extrapolating to ICH the promising results of minocycline treatment in other models of brain injury.
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Pain associated with cancer, particularly when tumors metastasize to bone, is often severe and debilitating. Better understanding of the neurobiological mechanisms underlying cancer pain will likely lead to the development of more effective treatments. The aim of this study was to characterize changes in response properties of nociceptive dorsal horn neurons following implantation of fibrosarcoma cells into and around the calcaneus bone, an established model of cancer pain. ⋯ Specifically, the proportion of WDR neurons that exhibited ongoing activity and their evoked discharge rates were greater in tumor-bearing than in control mice. In addition, WDR neurons exhibited lower response thresholds for mechanical and heat stimuli, and increased responses to suprathreshold mechanical, heat, and cold stimuli. Our findings show that sensitization of WDR neurons contributes to cancer pain and supports the notion that the mechanisms underlying cancer pain differ from those that contribute to inflammatory and neuropathic pain.