The cerebral microcirculation in focal ischemia and reperfusion
The role of the microcirculation and of the inflammatory response in secondary brain damage from cerebral ischemia is hardly understood. Objective of the study was to assess leukocyte-endothelium interactions (LEI), functional capillary density (FCD), and the microvascular patency in the reperfusion period after an acute ischemic insult. Focal ischemia was induced in gerbils by transient (2 h) ligation of the left CCA. Only animals with a reduction of rCBF to < 10 % baseline (n=8) were studied in comparison with sham operated controls (n=7) as determined by laser-doppler flowmetry. A transdural window was implanted for observation of the brain surface by intravital microscopy before, during and up to 3 h following ischemia. FITC-Dextran and Rhodamine 6G were i.v. administered as fluorescence dyes for contrast enhacement of blood vessels and labeling of leukocytes. A brief but significant increase in the number of rolling leukocytes (rollers) was found at 5 (7.7 ± 4.2) and 30 min (6.4 ± 2.4 / 100 μm x min) of postischemic reperfusion. Subsequently, however, the number of rollers declined reaching the control level. Leukocytes firmly attached to the endothelium of postcapillary venules were also shortly increased after ischemia, albeit without reaching statistical significance. The number of perfused postcapillary venules (8–20 μm) was decreased to 44 ± 18 % at 2 h of ischemia. The recovery of the venular patency and, thus, perfusion was significantly delayed, i.e. until 1h of reperfusion. With onset of ischemia FCD decreased from 168 ± 10 cm-1 to 7 ± 5 cm-1 (p<0.05) and did not recover with the ongoing reperfusion during the whole postischemic observation period (3 h). Activation of LEI as inflammatory response was limited to the immediate reperfusion period (5–30 min) only, rendering its pathophysiological significance questionable. On the other side FCD was drastically reduced and did not recover in animals with dense focal ischemia (<10%), with a delay of reperfusion of small venules for 1h or more. The marked disturbances of the microcirculation are most likley involved in the maturation of ischemic brain damage and may, thus, represent a promising target for therapeutic intervention.