Current concepts on reperfusion injury following focal cerebral ischemia

Reperfusion injury has become a scientific problem of increasing importance, in part because of recent developments of thrombolytic therapy. The mechanisms of reperfusion injury following focal cerebral ischemia, however, are not known in detail. Recent studies strongly suggest that reactive oxygen species (ROS) and calcium overload play an important role in reperfusion injury and that pharmacological interventions against calcium- or free radical-mediated damage could extend the therapeutic window in cerebral ischemia/reperfusion. The mediators involved are known to induce a mitochondrial permeability transition (PT) during the reperfusion period, which is associated with uncoupling of mitochondrial respiration, loss of mitochondrial membrane potential, and a burst production of ROS, leading to cellular death. The mitochondrial PT is considered to be a key process in reperfusion injury following cerebral ischemia, as also observed in other organs such as heart and liver. Pharmacological modulation of mitochondrial permeability changes have the potential to reduce tissue damage due to reperfusion.