Cerebral Ischemia Reperfusion Injury

Ischemia-reperfusion injury is a common feature of ischemic stroke, which occurs when blood supply is restored after a period of ischemia. Reperfusion can be achieved either by Thrombolysis using thrombolytic reagents such as tissue plasminogen activator (tPA), or through mechanical removal. Cerebral ischemia can induce inflammation with generation of Nf-kb, adhesion molecules, and upregulation of toll-like receptors while reperfusion generates reactive oxygen species (ROS) and opening of mitochondrial pore as well as inflammation and apoptosis. Nrf2 has neuroprotective role via increasing gene expression of anti-oxidant elements as well as anti-inflammatory effects. Further, Nrf2 activators were found to inhibit HMGB1 induced inflammation and ROS induce cerebral damage, as well as reduce p38 MAPK upregulation that can reduce NF-kB expression.