Neuropharmacology
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Impact to the head or rapid head acceleration-deceleration can cause traumatic brain injury (TBI) with a characteristic pathology of traumatic axonal injury (TAI) and secondary damage in white matter tracts. Myelin and oligodendrocyte lineage cells have significant roles in the progression of white matter pathology after TBI and in the potential for plasticity and subsequent recovery. The myelination pattern of specific brain regions, such as frontal cortex, may also increase susceptibility to neurodegeneration and psychiatric symptoms after TBI. ⋯ Thus, effective remyelination and myelin remodeling may be neurobiological substrates of plasticity in neuronal circuits that require long-distance communication. This perspective integrates findings from multiple contexts to propose a model of myelin and oligodendrocyte lineage cell relevance in white matter injury after TBI. This article is part of the Special Issue entitled 'Oligodendrocytes in Health and Disease'.
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Ischemia is a multifactorial pathology characterized by different events evolving in the time. After ischemia a primary damage due to the early massive increase of extracellular glutamate is followed by activation of resident immune cells, i.e microglia, and production or activation of inflammation mediators. Protracted neuroinflammation is now recognized as the predominant mechanism of secondary brain injury progression. ⋯ Among P2Y receptors, antagonists of P2Y12 receptors are of value because of their antiplatelet activity and possibly because of additional anti-inflammatory effects. Moreover strategies that modify adenosine or ATP concentrations at injury sites might be of value to limit damage after ischemia. This article is part of the Special Issue entitled 'Purines in Neurodegeneration and Neuroregeneration'.
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Neuropathic pain, a chronic pain condition following nerve damage and degeneration, involves aberrant excitability in the dorsal horn of the spinal cord. A growing body of evidence has shown that the aberrant excitability might not be a consequence merely of changes in neurons, but rather of multiple alterations in glial cells, such as microglia, the immune cells of the central nervous system. ⋯ Here, we describe recent advances in the understanding of neuron-microglia interactions by purinergic signaling in neuropathic pain following neurodegeneration. This article is part of the Special Issue entitled 'Purines in Neurodegeneration and Neuroregeneration'.
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Neuroimmune diseases have diverse symptoms and etiologies but all involve pathological inflammation that affects normal central nervous system signaling. Critically, many neuroimmune diseases also involve insufficient signaling/bioavailability of interleukin-10 (IL-10). IL-10 is a potent anti-inflammatory cytokine released by immune cells and glia, which drives the regulation of a variety of anti-inflammatory processes. ⋯ These exciting results have resulted in IL-10-targeted therapeutics being positioned for upcoming clinical trials for treating neuroimmune diseases, including neuropathic pain. Although further research is necessary to determine the full range of effects associated with IL-10-based therapy, evidence suggests IL-10 may be an invaluable target for the treatment of neuroimmune disease. This article is part of a Special Issue entitled 'Neuroimmunology and Synaptic Function'.
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Migraine is the most common neurological disorder and one of the most common chronic pain conditions. Despite its prevalence, the pathophysiology leading to migraine is poorly understood and the identification of new therapeutic targets has been slow. Several processes are currently thought to contribute to migraine including altered activity in the hypothalamus, cortical-spreading depression (CSD), and afferent sensory input from the cranial meninges. ⋯ Although few studies have directly examined a role of ASICs in migraine, studies directly examining a connection have generated promising results including efficacy of ASIC blockers in both preclinical migraine models and in human migraine patients. The purpose of this review is to discuss the pathophysiology thought to contribute to migraine and findings that implicate decreased pH and/or ASICs in these events, as well as propose issues to be resolved in future studies of ASICs and migraine. This article is part of the Special Issue entitled 'Acid-Sensing Ion Channels in the Nervous System'.