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(Stroke. 2004;35:2675.)
© 2004 American Heart Association, Inc.

Articles

Ischemic Preconditioning

Introduction

From the Canadian Stroke Network (A.H.), Ottawa, Canada; and the Dow Neurobiology Laboratory (R.S.), Portland Ore.

Correspondence to Dr Antoine M. Hakim, Canadian Stroke Network, Head, Neuroscience Research and University Chair, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5. E-mail ahakim@ohri.ca

An extract of the first 250 words of the full text is provided, because this article has no abstract.

The quest for effective therapeutics for the treatment of stroke has resulted in more than a dozen clinical trials of putative neuroprotective drugs. None has proven successful. Although trial design may be a factor in these failures, the negative results of these attempts to find effective exogenous therapies for cerebral ischemia have stimulated research for endogenous modulators of neuroprotection. Such endogenous modulators produce the phenomenon of ischemic tolerance/preconditioning. Thus, stressors seem capable of producing a dose–response relationship in the brain where mild to severe stress first produces the tolerance phenomenon and increasingly severe stress culminates in apoptosis and finally pan- necrosis.¹ Tolerance-inducing stress may require an intensity resulting in some degree of injury at a cellular level, eg, protein denaturation.

The tolerance inducing stimulus may result from diverse stressors, including global ischemia, focal ischemia, hyperbaric oxygenation, inflammation, epileptic seizures, cortical spreading depression, hypothermia, hyperthermia, or cerebellar stimulation. The relevance to ischemic neuroprotection is found in the multiple examples of "cross-tolerance" described in which the tolerance-inducing stress protects against a different potentially injurious stress, eg, brief seizures protect against ischemia and mild degrees of ischemia protect against epileptic brain injury.

Although it is generally assumed that the preconditioning phenomenon was first described in the heart in the 1980s^2,3 and not until 1990⁴ in the brain, whole body traumatic stress producing "resistance" to subsequent trauma was described in 1943.⁵ Whereas the experiments regarding trauma might involve multiple organs in addition to brain, tolerance in brain to ischemia was described in 1964, 20 . . . [Full Text of this Article]