Extending injury- and disease-resistant CNS phenotypes by repetitive epigenetic conditioning

Frontiers in Neurology
Jeffrey M Gidday

Abstract

Significant reductions in the extent of acute injury in the CNS can be achieved by exposure to different preconditioning stimuli, but the duration of the induced protective phenotype is typically short-lasting, and thus is deemed as limiting its clinical applicability. Extending the period over which such adaptive epigenetic changes persist - in effect, expanding conditioning's "therapeutic window" - would significantly broaden the potential applications of such a treatment approach in patients. The frequency of the conditioning stimulus may hold the key. While transient (1-3 days) protection against CNS ischemic injury is well established preclinically following a single preconditioning stimulus, repetitively presenting preconditioning stimuli extends the duration of ischemic tolerance by many weeks. Moreover, repetitive intermittent postconditioning enhances post-ischemic recovery metrics and improves long-term survival. Intermittent conditioning is also efficacious for preventing or delaying injury in preclinical models of chronic neurodegenerative disease, and for promoting long-lasting functional improvements in a number of other pathologies as well. Although the detailed mechanisms underlying these protracted kinds of neu...Continue Reading

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Apr 10, 2016·Experimental Eye Research·Jie FanCraig E Crosson
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Aug 12, 2018·Journal of Neuroscience Research·Vittorio CalabreseEdward J Calabrese
Aug 15, 2017·Frontiers in Physiology·Michal Horowitz

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BETA
environmental stress

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