There is extensive evidence that the restoration of blood flow following cerebral ischemia contributes greatly to
the pathophysiology of ischemia mediated brain injury. The initiating stimulus of reperfusion injury is believed to be the
excessive production of reactive oxygen (ROS) and nitrogen (RNS) species by the mitochondria. ROS and RNS
generation leads to mitochondrial protein, lipid and DNA oxidation which impedes normal mitochondrial physiology and
initiates cellular death pathways. However not all ROS and RNS production is detrimental. It has been demonstrated that
low levels of ROS production are protective and may serve as a trigger for activation of ischemic preconditioning.
Ischemic preconditioning is a neuroprotective mechanism which is activated upon a brief sublethal ischemic exposure and
is sufficient to provide protection against a subsequent lethal ischemic insult. Numerous proteins and signaling pathways
have been implicated in the ischemic preconditioning neuroprotective response. In this review we examine the origin and
mechanisms of ROS and RNS production following ischemic/reperfusion and the role of free radicals in modulating
proteins associated with ischemic preconditioning neuroprotection.
Keywords: Epsilon PKC, HIF, Ischemic preconditioning, Nrf2, Reactive oxygen species, Sirtuin, SIRT1, Reperfusion
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