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Int J Physiol Pathophysiol Pharmacol 2013;5(2):61-72

Review Article
Using hormetic strategies to improve ischemic preconditioning and
postconditioning against stroke

Heng Zhao, Sungpil Joo, Weiying Xie, Xunming Ji

Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305-5327, USA; Xuanwu Hospital, Beijing Capital
Medical University, Beijing, China

Received February 14, 2013; Accepted April 31, 2013; Epub May 27, 2013; Published June 15, 2013

Abstract: Both ischemic preconditioning (IPreC) and ischemic postconditioning (IPostC) trigger endogenous neuroprotective
mechanisms in cerebral ischemia. IPreC is defined as a brief ischemia that protects against a subsequent severe ischemia, while
IPostC refers to a series of brief cerebral blood vessel occlusions performed at reperfusion following an ischemic event. Hormesis
describes a biphasic dose-response relationship in toxicology, where a low dose of toxicant stimulates and a high dose inhibits
biological responses. In general, any minor stress will stimulate a biological system to generate an adaptive response; in most cases,
if not all, such an adaptive response to a minor stress is beneficial to the biological system. Proponents of hormesis suggest that this
effect is independent of any models, either in vivo or in vitro, from animal, plant, fungi, yeast, to bacteria, by any measurement of end
points, survival ratio or time, growth, tissue repair, life span, cognition, learning and memory. In this review, we examine whether IPreC
and IPostC are actually sub-forms of hormesis and whether quantitative hormetic strategies can be used to study IPreC and IPostC. By
integrating the concepts of IPreC and IPostC with hormesis, we aim to broaden the avenues leading to clinical translation of IPreC and
IPostC in stroke treatment. (IJPPP1302002).

Keywords: Ischemic postconditioning, preconditioning, stroke, hormesis

Address correspondence to: Dr. Heng Zhao, Department of Neurosurgery, Stanford University School of Medicine, MSLS Bldg., Room
P306, 1201 Welch Rd., Room P306, Stanford, CA 94305-5327. Phone: 650-725-7723; Fax: 650-498-4134; E-mail: hzhao@stanford.edu