title: Cerebral Ischemic Preconditioning: the Road So Far….
abstract: Cerebral preconditioning constitutes the brain's adaptation to lethal ischemia when first exposed to mild doses of a subtoxic stressor. The phenomenon of preconditioning has been largely studied in the heart, and data from in vivo and in vitro models from past 2-3 decades have provided sufficient evidence that similar machinery exists in the brain as well. Since preconditioning results in a transient protective phenotype labeled as ischemic tolerance, it can open many doors in the medical warfare against stroke, a debilitating cerebrovascular disorder that kills or cripples thousands of people worldwide every year. Preconditioning can be induced by a variety of stimuli from hypoxia to pharmacological anesthetics, and each, in turn, induces tolerance by activating a multitude of proteins, enzymes, receptors, transcription factors, and other biomolecules eventually leading to genomic reprogramming. The intracellular signaling pathways and molecular cascades behind preconditioning are extensively being investigated, and several first-rate papers have come out in the last few years centered on the topic of cerebral ischemic tolerance. However, translating the experimental knowledge into the clinical scaffold still evades practicality and faces several challenges. Of the various preconditioning strategies, remote ischemic preconditioning and pharmacological preconditioning appears to be more clinically relevant for the management of ischemic stroke. In this review, we discuss current developments in the field of cerebral preconditioning and then examine the potential of various preconditioning agents to confer neuroprotection in the brain.
authors.affiliation: School of Biotechnology, DBT-Centre for Bioinformatics, National Institute of Technology Calicut, Calicut, 673601, India.
authors.forename: N
authors.initials: N
authors.lastname: Thushara Vijayakumar
authors.affiliation: School of Biotechnology, DBT-Centre for Bioinformatics, National Institute of Technology Calicut, Calicut, 673601, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Sangwan
authors.affiliation: School of Biotechnology, DBT-Centre for Bioinformatics, National Institute of Technology Calicut, Calicut, 673601, India.
authors.forename: Bhargy
authors.initials: B
authors.lastname: Sharma
authors.affiliation: Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK.
authors.forename: Arshad
authors.initials: A
authors.lastname: Majid
authors.affiliation: School of Biotechnology, DBT-Centre for Bioinformatics, National Institute of Technology Calicut, Calicut, 673601, India. rajanikant@nitc.ac.in.
authors.forename: G K
authors.initials: GK
authors.lastname: Rajanikant
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000235:genetics / Q000473:pathology*; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic; D006801:Humans; D019194:Ischemic Preconditioning
keywords: Cerebral ischemia; Epigenetics; Genomic reprogramming; Ischemic tolerance; Neuroprotection; Preconditioning