From Rapid to Delayed and Remote Postconditioning: The Evolving Concept of Ischemic Postconditioning in Brain Ischemia

Abstract

Ischemic postconditioning is a concept originally defined to contrast with that of ischemic preconditioning. While both preconditioning and postconditioning confer a neuroprotective effect on brain ischemia, preconditioning is a sublethal insult performed in advance of brain ischemia, and postconditioning, which conventionally refers to a series of brief occlusions and reperfusions of the blood vessels, is conducted after ischemia/reperfusion. In this article, we first briefly review the history of preconditioning, including the experimentation that initially uncovered its neuroprotective effects and later revealed its underlying mechanisms-of-action. We then discuss how preconditioning research evolved into that of postconditioning – a concept that now represents a broad range of stimuli or triggers, including delayed postconditioning, pharmacological postconditioning, remote postconditioning – and its underlying protective mechanisms involving the Akt, MAPK, PKC and KATP channel cell-signaling pathways. Because the concept of postconditioning is so closely associated with that of preconditioning, and both share some common protective mechanisms, we also discuss whether a combination of preconditioning and postconditioning offers greater protection than preconditioning or postconditioning alone.

Ischemic Postconditioning Relieves Cerebral Ischemia and Reperfusion Injury Through Activating T-LAK Cell–Originated Protein Kinase/Protein Kinase B Pathway in Rats

“…1 A remarkably neuroprotective role for both remote IPostC and brain IPostC have been demonstrated by us and other groups. [2][3][4][5] Oxidative stress from reactive oxygen species has long been considered as a key deleterious factor in cerebral I/R injury, 6 and one of the mechanisms of IPostC against I/R injury is its antioxidative function.…”

Excitotoxicity: An Organized Crime at The Cellular Level

“…The decrease in ATP levels and increase in free radical production boosts activation of the various subtypes of PKC [79]. Activation of γPKC triggers its translocation to the neuronal membrane, where it enhances postsynaptic NMDAR Glu sensitivity.…”

MCPIP mediates preconditioning protection against ischemia

“…Ischemia tolerance consists of an early phase that occurs within minutes after ischemia induction followed by a delayed phase that lasts for hours or even days. Mechanisms underlying delayed preconditioning that produces a potent neuroprotection, may suggest novel treatment for ischemic stroke 18,19 . EA pretreatment-induced neuroprotection is related to the suppression of inflammatory processes in the ischemic area, and this suppression is probably mediated via induction of MCPIP 19 .…”