CALCIUM-METABOLISM OF FOCAL AND PENUMBRAL TISSUES IN RATS SUBJECTED TO TRANSIENT MIDDLE CEREBRAL-ARTERY OCCLUSION

The present experiments were undertaken to define changes in tissue ca lcium metabolism in focal and perifocal (''penumbral'') tissues follow ing 2 h of transient middle cerebral artery occlusion (MCAO) in rats, induced with an intraluminal filament occlusion technique. The extrace llular calcium concentration ([Ca2+](e)) was measured with ion-selecti ve microelectrodes in neocortical focus and penumbra. For measurement of total tissue calcium content, tissue samples from these areas were collected and analyzed with atomic absorption spectrometry. During MCA O, [Ca2+](e) in a neocortical focal area fell from a normal value of a bout 1.2 mM to values around 0.1 mM, suggesting translocation of virtu ally all extracellular calcium to intracellular fluids. Recirculation was accompanied by re-extrusion of calcium within 5-7 min; however, [C a2+](e) never returned to normal but stabilized at about 50% of the co ntrol value for the first 6 h, and decreased further after 24 h. In pe numbral areas, [Ca2+](e) showed the expected transient decreases assoc iated with spreading depression-like (or ischemic) depolarization wave s. Recirculation was followed by return of [Ca2+](e) towards normal va lues. In the focus, water content increased from about 79% to about 80 .4% at the end of the 2-h period of ischemia. After 2 h and 4 h of rec irculation, the edema was aggravated (mean values 81.9% and 81.2%, res pectively). After 6 h and 24 h, the edema was more pronounced (83.6% a nd 83.8%, respectively). In the penumbra, no significant edema was obs erved until 6 h and 24 h of recirculation. The total tissue calcium co ntent in the focus (expressed by unit dry weight) increased at the end of the ischemia period demonstrating calcium translocation from blood to tissue. After 6 h and 24 h, the content increased two-to threefold , compared with control. Changes in the penumbra were qualitatively si milar but less pronounced, and a significant increase was not observed until after 6 h of recirculation. The results suggest that 2 h of MCA O leads to a profound perturbation of cell calcium metabolism. In foca l areas, cells fail to extrude the calcium that is gradually accumulat ed during reperfusion and show massive calcium overload after the firs t 4-6 h of recirculation. Penumbral tissues show a similar increase in calcium concentration after 6 h of recirculation.