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(Stroke. 2008;39:2910.)
© 2008 American Heart Association, Inc.

Topical Review

Metabolic Downregulation

A Key to Successful Neuroprotection?

Midori Yenari, MD; Kazuo Kitagawa, MD; Patrick Lyden, MD Miguel Perez-Pinzon, PhD

From the Department of Neurology (M.Y.), University of California, San Francisco and the San Francisco Veterans Affairs Medical Center, San Francisco, Calif; the Department of Neurology (K.K.), Osaka University Graduate School of Medicine, Suita, Osaka, Japan; Neurology and Research Services of the San Diego Veteran’s Administration Medical Center and the Department of Neurosciences (P.L.), University of California, San Diego; and the Department of Neurology (M.P.-P.), University of Miami, Fla.

Correspondence to Midori A. Yenari, MD, Department of Neurology, UCSF, Neurology (127) VAMC, 4150 Clement St, San Francisco, CA 94121. E-mail yenari{at}alum.mit.edu

Eng Lo PhD Section Editor

Background and Purpose— The search for effective neuroprotectants remains frustrating, particularly with regard to specific pharmaceuticals. However, laboratory studies have consistently shown remarkable neuroprotection with 2 nonpharmacological strategies—therapeutic hypothermia and ischemic preconditioning. Recent studies have shown that the mechanism of protection underlying both of these treatments is correlated to downregulation of cellular and tissue metabolism. Thus, understanding the mechanisms underlying such robust protective effects could lead to appropriate translation at the clinical level. In fact, hypothermia is already being used at many centers to improve neurological outcome from cardiac arrest.

Methods— A systematic review of both topics is presented in terms of underlying pathophysiological mechanisms and application at the clinical level.

Results— Although the mechanisms of protection for both therapeutic strategies are multifold, both share features of downregulating metabolism. Both therapeutic strategies are robust neuroprotectants, but translating them to the clinical arena is challenging, though not impossible, and clinical studies have shown or suggest benefits of both treatments.

Conclusions— The strategy of metabolic downregulation should be further explored to identify effective neuroprotectants that can be easily applied clinically.

Key Words: cerebral ischemia • ischemic tolerance • hypothermia