Neuropharmacology
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Neuroprotection for ischemic stroke refers to strategies, applied singly or in combination, that antagonize the injurious biochemical and molecular events that eventuate in irreversible ischemic injury. There has been a recent explosion of interest in this field, with over 1000 experimental papers and over 400 clinical articles appearing within the past 6 years. These studies, in turn, are the outgrowth of three decades of investigative work to define the multiple mechanisms and mediators of ischemic brain injury, which constitute potential targets of neuroprotection. ⋯ Among promising ongoing efforts, therapeutic hypothermia, high-dose human albumin therapy, and hyperacute magnesium therapy are considered in detail. The potential of combination therapies is highlighted. Issues of clinical-trial funding, the need for improved translational strategies and clinical-trial design, and "thinking outside the box" are emphasized.
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The subventricular zone (SVZ) of the lateral ventricle contains neural stem and progenitor cells that generate neuroblasts, which migrate to the olfactory bulb where they differentiate into interneurons. Ischemic stroke induces neurogenesis in the SVZ and these cells migrate to the boundary of the ischemic lesion. This article reviews current data on cytokinetics, signaling pathways and vascular niche that are involved in processes of proliferation, differentiation, and migration of neural progenitor cells after stroke.
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Experimental research into brain ischemia contributes substantially to the understanding of ischemic injury mechanisms but suffers from its limited relevance for clinical treatment strategies. One of the reasons is the use of experimental models and methods that do not or only partially replicate the pathophysiology of naturally occurring brain ischemia. ⋯ Particular emphasis is given to the pathophysiological particularities of the various ischemia models, the application of imaging methods for the reliable differentiation between infarct core, penumbra, benign oligemia and normal tissue, as well as to the final outcome of experimental interventions. Based on this analysis, recommendations are given to improve the translational power of brain ischemia-related experimental research.
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The amygdala plays an important role in the emotional-affective component of pain and in pain modulation. Group III metabotropic glutamate receptors (mGluRs) regulate pain-related activity in the amygdala, but the behavioral consequence and contribution of individual subtypes are not known yet. This study determined the effects of mGluR7 and mGluR8 activation in the central nucleus of the amygdala (CeA) on nocifensive and affective pain responses and on pain-related anxiety-like behavior of adult rats. ⋯ An mGluR8-selective agonist (S-3,4-dicarboxyphenylglycine, S-3,4-DCPG, 10microM) had no effect in normal animals but inhibited the increased spinal reflex responses and audible and ultrasonic vocalizations of arthritic rats. S-3,4-DCPG also increased the open-arm choices of arthritic rats, suggesting anxiolytic effects. The results suggest that under normal conditions mGluR7, but not mGluR8, facilitates pain responses and has anxiogenic properties whereas mGluR8, but not mGluR7, can inhibit nocifensive and affective behaviors and anxiety in a model of arthritic pain.