PHOTOTHROMBOTIC INFARCTION TRIGGERS MULTIPLE EPISODES OF CORTICAL SPREADING DEPRESSION IN DISTANT BRAIN-REGIONS

The purposes of this study were to determine whether cortical spreadin g depression occurs outside of the infarct produced by photothrombotic vascular occlusion, and also the direction of spreading. Focal cerebr al thrombotic infarction was produced by irradiating the exposed skull of anesthetized rats with green light (560 nm) following systemic inj ection of rose bengal dye. At proximal sites (similar to 2 mm anterior to the infarct border), transient, severe hyperemic episodes (THEs) l asting 1-2 min were intermittently recorded. THE frequency was greates t in the first hour and declined over a 3-h period. THEs were accompan ied (and usually preceded) by a precipitous rise in [K+](0) (from simi lar to 3 to >40 mM) and were associated with increases in local tissue oxygen tension (tPO(2)). Following the rise in [K+](0), clearance of [K+](0) to its pre-THE baseline preceded baseline recovery of CBF. The se data indicate that THEs were reactive to physiologic events resembl ing cortical spreading depression (CSD), which provoked increased dema nd for oxygen and blood flow, and which spread from proximal sites to areas more distal (similar to 4 mm) from the rim of the evolving infar ct. MK-801 (1 mg/kg, i.v.) inhibited subsequent CSD-like episodes. We conclude that photothrombosis-induced ischemia provoked CSD which was triggered either within the infarct core or in the infarct rim and spr ead to more distal sites. Whether multiple episodes of CSD during infa rct generation are responsible for the remote consequences of focal br ain injury remains to be determined. .