title: Metabolic downregulation: a key to successful neuroprotection?
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco Veterans Affairs Medical Center, San , San Francisco, CA 94121, USA. yenari@alum.mit.edu
authors.forename: Midori
authors.initials: M
authors.lastname: Yenari
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kitagawa
authors.forename: Patrick
authors.initials: P
authors.lastname: Lyden
authors.forename: Miguel
authors.initials: M
authors.lastname: Perez-Pinzon
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000502:physiology; D002986:Clinical Trials as Topic; D015536:Down-Regulation; D006801:Humans; D007036:Hypothermia, Induced / Q000379:methods; D019194:Ischemic Preconditioning / Q000379:methods; D009410:Nerve Degeneration / Q000209:etiology / Q000517:prevention & control*; D020521:Stroke / Q000150:complications / Q000628:therapy*