PATHWAYS OF CEREBRAL CALCIUM ACCUMULATION IN A MODEL OF FOCAL ISCHEMIA IN RATS

Focal cerebral ischemia was produced in anesthetized rats by a minimal ly invasive photothrombic procedure. Rose bengal was injected into a t ail vein and the right middle cerebral artery region irradiated for 5 min through the skull with the right common carotid artery temporarily occluded. This resulted in focal cerebral infarction which was restri cted to the cortex as shown by autoradiography and histopathology. Ede ma and the uptake of Ca-45 were determined 1, 3 or 24 hours after isch emia in different regions of the brain, ipsilateral and contralateral to the ischemic injury, the tracer uptake at three time points alter a dministration. The values of Ca-45 uptake and edema were the highest a t the center of the infarction. Simulation of the Ca-45 uptake kinetic s in the 24 h post-ischemic group, enabled the determination of the co ntributions of different physiological pathways to cerebral calcium fl ux. The results indicated the breakdown of the blood-brain barrier to be primarily responsible for the increased uptake of the tracer by the ischemic cortex. A concomitant, presumably intracellular, sequestrati on resulted in a ca. 16-fold increase in the tissue pool of exchangeab le calcium. Simulation such as proposed here would be of value in pred icting the outcome of tracer accumulation in pathological situations.