REPERFUSION DAMAGE FOLLOWING FOCAL ISCHEMIA - PATHOPHYSIOLOGY AND THERAPEUTIC WINDOWS

The mechanisms of reperfusion damage following focal cerebral ischemia are not known in detail. Recent results, however, strongly suggest th at reactive oxygen species (ROS), generated during the reperfusion per iod, may trigger the reperfusion injury. Mitochondrial calcium overloa d and a permeability transition (PT) of the inner mitochondrial membra ne have been shown to play an important role in production of ROS by t he mitochondria. The immunosuppressant cyclosporin A (CsA), which inhi bits mitochondrial PT, protects against delayed neuronal necrosis of t he hippocampal CAI sector following transient forebrain/global ischemi a. In focal ischemia (''stroke''), expression of adhesion molecules su ch as intercellular adhesion molecule-1 (ICAM-1) may lead to productio n of ROS by polymorphonuclear (PMN) leukocytes, which suggests the inv olvement of inflammatory and immunological reactions in reperfusion da mage. The spin trap alpha-phenyl-N-tert-butyl nitrone (PBN) reduces in farct size and prevents a secondary mitochondrial dysfunction due to r eperfusion, probably scavenging free radicals at the blood-endothelial cell interface. (C) 1997 Wiley-Liss, Inc.