Journal of neuroscience research
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Many therapies that have been developed for acute spinal cord injury (SCI) either influence or are influenced by posttraumatic inflammation. Many such therapies have reportedly produced promising neurologic benefits in animal models of SCI, but demonstrating convincing efficacy in human clinical trials has remained elusive. This discrepancy may be related in part to differences in the inflammatory response to SCI between human patients and the widely studied rodent models. ⋯ IL-6, IL-8, and MCP-1 were released in an injury-dependent manner in both the rodent model of SCI and the human condition. In this regard, similar patterns of expression were observed for a number of inflammatory cytokines after SCI in rodent spinal cords and in human CSF. Such proteins may therefore have potential utility as biomarkers and surrogate outcome measures for evaluating biological response to therapeutic interventions.
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Differentiation and self-renewal are two primary properties that characterize stem cells. Differentiation of neural stem/precursor cells (NSPCs) gives rise to multiple neural lineages, including neurons, astrocytes, and oligodendrocytes. ⋯ The epigenetic modification of developmental genes, including alterations in DNA methylation, histone modifications, polycomb gene group and noncoding RNA expression, which are passed on through successive cell divisions, has proved to be one of the major mechanisms determining the fate of neural stem cells. Here, we review the diverse epigenetic pathways that decide whether NSPCs undergo proliferation or differentiation into different neuronal cell lineages.
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Previous studies have suggested that the release of brain-derived neurotrophic factor (BDNF) from microglia in spinal cord is necessary for maintaining pain hypersensitivity after nerve injury. However, little is known about its role in cancer-induced bone pain (CIBP), which is in some ways unique. This study demonstrates a critical role of minocycline (a potent inhibitor of microglial activation)-modulated BDNF in the induction and maintenance of behavioral hypersensitivity in a rat model of CIBP. ⋯ However, at the late stage (from day 10 to day 12), intrathecal minocycline had no effect. Moreover, the expression of OX-42 and BDNF under CIBP, peaking on day 6, were all reduced after minocycline injection from day 4 to day 6. The ability of minocycline-induced reduction of BDNF in the induction of behavioral hypersensitivity could provide an opportunity for alleviating CIBP.
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Gap junctions are specialized transmembrane channels that allow rapid electrical signalling and direct intercellular communication for maintenance and coordination of normal cellular activities and homeostasis. Although gap junction channels in the nervous system mediate intercellular coupling between glial cells and between neurons, they also contribute to the spread of secondary damage and inflammation under pathological conditions. ⋯ In this Mini-Review, we highlight recent studies demonstrating the dynamic plasticity of gap junctions in response to nervous system injury and the effects of gap junction blockade on neuronal survival and modulation of pain in animal models of neuropathic and inflammatory pain. The involvement of dorsal root ganglia and spinal cord gap junctions in mediating chronic pain and the potential for targeting connexins as a novel modality for the treatment of intractable pain syndromes arising from nervous system injury and disorders are discussed.
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Male and female rodents respond differently to acute stress. We tested our hypothesis that this sex difference is based on differences in stress sensitivity of forebrain areas, by determining possible effects of a single acute psychogenic stressor (1-hr restraint stress) on neuronal gene expression (c-Fos and FosB immunoreactivities), storage of corticotropin-releasing factor (CRF) immunoreactivity, and CRF production (CRF mRNA in situ hybridization) as well as the expression of genes associated with epigenetic processes (quantitative RT-PCR) in the rat paraventricular nucleus (PVN), the oval and fusiform subdivisions of the bed nucleus of the stria terminalis (BSTov and BSTfu, respectively), and the central amygdala (CeA), in both males and females. ⋯ In the BSTfu, males and females showed similar stress-induced increases in c-Fos and FosB, whereas in the CeA, both sexes revealed similar increases in c-Fos and in CRF mRNA. We conclude that male and female rats differ in their reactivity to acute stress with respect to possibly epigenetically mediated (particularly in the PVN) neuronal gene expression and neuropeptide dynamics (PVN and BSTov) and that this difference may contribute to the sex dependence of the animal's physiological and behavioral responses to an acute stressor.