Post-ischemic brain damage: effect of ischemic preconditioning and postconditioning and identification of potential candidates for stroke therapy.
Because clinical trials of pharmacological neuroprotective strategies in stroke have been disappointing, attention has turned to the brain's own endogenous strategies for neuroprotection. Two endogenous mechanisms have been characterized so far, namely ischemic preconditioning and ischemic postconditioning. The neuroprotective concept of preconditioning is based on the observation that a brief, noninjurious episode of ischemia is able to protect the brain from a subsequent longer ischemic insult. Recently, a hypothesis has been offered that modified reperfusion subsequent to a prolonged ischemic episode may also confer ischemic neuroprotection, a phenomenon termed postconditioning. Many pathways have been proposed as plausible mechanisms to explain the neuroprotection offered by preconditioning and postconditioning. Unfortunately, so far, none of them has clearly identified the mechanism involved in preconditioning and postconditioning. The present article will review the main mechanisms reported to date to explain the neuroprotective effect of both ischemic preconditioning and postconditioning.
Pignataro
Giuseppe
G
Division of Pharmacology, Department of Neuroscience, School of Medicine, Federico II University of Naples, Italy.
Scorziello
Antonella
A
Di Renzo
Gianfranco
G
Annunziato
Lucio
L
D001921:Brain / Q000201:enzymology / Q000503:physiopathology; D001925:Brain Damage, Chronic / Q000188:drug therapy / Q000209:etiology*; D002545:Brain Ischemia / Q000150:complications* / Q000188:drug therapy; D002560:Cerebrovascular Circulation / Q000502:physiology; D004734:Energy Metabolism; D006706:Homeostasis; D006801:Humans; D000860:Hypoxia / Q000209:etiology; D019194:Ischemic Preconditioning / Q000379:methods; D018696:Neuroprotective Agents / Q000627:therapeutic use; D009569:Nitric Oxide / Q000502:physiology; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism; D020521:Stroke / Q000188:drug therapy* / Q000209:etiology* / Q000401:mortality
D018696:Neuroprotective Agents; D024642:Potassium Channels, Voltage-Gated; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D000254:Sodium-Potassium-Exchanging ATPase