Real-time microcirculatory changes due to spreading depression under focal ischemia

Abstract

Laser-scanning confocal fluorescence microscopy was used to investigate microcirculatory influences of spreading depression (SD)-like depolarizations elicited by occlusion of the rat middle cerebral artery (MCA). Six rats underwent halothane anesthesia and mechanical ventilation. A closed cranial window was implanted over their frontoparietal cortex. They were placed under a Biorad Viewscan confocal microscope and intravenously given fluorescein isothiocyanate (FITC)-Dextran and FITC-labeled erythrocytes. The capillaries were visualized down to 200 μm below the brain surface and the images were video recorded (50/s). The MCA was occluded under the microscope using an intraluminal remotely controlled method and the reperfusion was induced 2 h later. Furthermore, the brains were histologically examined 24 h later. Under ischemia, the erythrocyte velocity through the capillaries was depressed by 35% and venous blood became highly sluggish. The arteriole diameter did not change significantly, however, the direction of arteriolar blood flow was episodically and transiently reversed. During spontaneous SD-like depolarization, the arteriole diameter significantly increased (+19% vs. MCAO) while capillary erythrocyte velocity was further depressed by 15%. This decrease in velocity was more pronounced (25%) when depolarization were associated with transient reversal of arteriolar flow. Following reperfusion, microcirculatory variables rapidly returned to the baseline. All rats exhibited infarcts 24 h after the occlusion. These results indicate that SD-like depolarizations have an adverse influence on penumbral microcirculation, i.e., a reduction in capillary perfusion by erythrocytes, despite arteriolar dilatation.