Preconditioning the Human Brain: Practical Considerations for Proving Cerebral Protection
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PERSPECTIVE PAPER
Preconditioning the Human Brain: Practical Considerations for Proving Cerebral Protection Sebastian Koch
Published online: 15 May 2010 # Springer Science+Business Media, LLC 2010
Abstract Ischemic preconditioning has evolved as one of the most powerful strategies for cerebral protection in laboratory models of ischemia. Translating the success of laboratory studies to human cerebral protection will necessitate an approximation of laboratory conditions. This would require a practical, easily implemented method of preconditioning and clinical settings in which cerebral ischemia is anticipated, thereby allowing cerebral preconditioning prior to ischemia onset. Remote limb ischemic preconditioning is readily instituted and used in several ongoing cardiac studies for ischemic myocardial protection. It is a potentially promising intervention for brain protection as well. Suitable clinical settings, in which a preliminary study of ischemic preconditioning in neurological disorders appears feasible, include carotid endarterectomy or stenting, cardiac surgery, and subarachnoid hemorrhage with the accompanying risk of vasospasm. These are settings, in which there is substantial risk of brain ischemia, which occurs over a short and predictable period, allowing for preconditioning to be implemented prior to ischemia onset. Keywords Ischemic preconditioning . Limb preconditioning . Neuroprotection
Introduction It is well established that organisms subjected to mild forms of environmental stress become tolerant to an otherwise
S. Koch (*) Department of Neurology, University of Miami, 1150 NW 14th Street, PAC, Suite#609, Miami, FL 33136, USA e-mail: [email protected]
noxious environment. A simple example is animals exposed to sublethal temperature elevations are able to survive at temperatures, which otherwise would be lethal. The induction of such tolerance confers basic survival mechanisms to prokaryotic and eukaryotic cells. These protective mechanisms are highly preserved across species and seen with many different forms of stress. The deliberate induction of such tolerance is known as preconditioning as the inducing stimulus precedes the noxious or lethal insult (Fig. 1a, b). Many different stress stimuli lead to preconditioning and include drugs (pharmaceutical preconditioning), mild forms of ischemia (ischemic preconditioning), hypoxia/hyperoxia, and hypo- and hyperthermia [1, 2]. Of these, ischemic preconditioning has emerged as one of the most powerful protective anti-ischemia mechanisms known. There has been substantial investment in the laboratory study of preconditioning. Numerous studies, across multiple different organs and experimental models, have shown protection through ischemic preconditioning. Cerebral protection through ischemic preconditioning is widely achieved in many models of global and focal cerebral ischemia. However, the therapeutic potential of ischemic preconditioning in clinical practice has remained largely unexplored. The aim of this article is to consider practical steps
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