Background and Purpose-To study whether intravascular or hemodynamic factors contribute to the marked neuroprotective effect of albumin therapy in focal cerebral ischemia, 2 complementary methods were applied: laser-scanning confocal microscopy (LSCM) and laser-Doppler perfusion imaging (LDPI). Methods-In the LSCM study, Sprague-Dawley rats were anesthetized with halothane/nitrous oxide, and a cranial window was placed over the dorsolateral frontoparietal cortex. Rats received 2-hour middle cerebral artery occlusion (MCAO) by an intraluminal suture and were treated with human albumin (1.25 g/kg; nϭ4) or saline (nϭ3) after 30 minutes of recirculation. Video images of cortical vessels were continually acquired and were digitized offline to measure diameters and fluorescent erythrocyte velocities. In the LDPI study, cortical perfusion was measured in anesthetized SpragueDawley rats that received 2-hour MCAO and were treated with albumin (2.5 g/kg; nϭ6) or saline (nϭ5) at 30 minutes after recirculation. Results-In the LSCM study, MCAO was associated with arteriolar dilation and slowing of capillary and venular erythrocyte perfusion. During the first 15 to 30 minutes of postischemic recirculation, prominent foci of vascular stagnation developed within cortical venules, associated with thrombuslike foci and adherent corpuscular structures consistent in size with neutrophils. Saline administration failed to affect these phenomena, while albumin therapy was followed by significant increases in arteriolar diameter (Ϸ12%; Pϭ0.007) and by a prompt improvement of venular and capillary erythrocyte perfusion and a partial disappearance of adherent thrombotic material. Albumin therapy increased erythrocyte flow velocity in both capillaries (288Ϯ73% versus 76Ϯ18% in the saline group; Pϭ0.023) and venules (2.7-fold [Pϭ0.001] versus 1.0-fold in the saline group [PϭNS]). In the LDPI study, cortical perfusion declined during MCAO and rose initially with recirculation (to Ϸ135% of baseline) in both groups. Mean cortical perfusion improved slightly (Ϸ14%; PϭNS) in albumin-treated animals. Conclusions-These results reveal a beneficial effect of albumin therapy in reversing stagnation, thrombosis, and corpuscular adherence within cortical venules in the reperfusion phase after focal ischemia and support its utility in the treatment of acute ischemic stroke.

Background and Purpose-This study was designed to investigate the influence of peri-infarct depolarization elicited by occlusion of the middle cerebral artery on the dynamics of the microcirculation. Methods-The microcirculation in the frontoparietal cortex of 9 rats was visualized in real time through a closed cranial window with the use of laser-scanning confocal fluorescence microscopy combined with intravenous fluorescein isothiocyanate (FITC)-dextran and FITC-labeled erythrocytes. The direct current potential/electrocorticogram was continuously monitored. Intraluminal focal ischemia was induced for 2 hours in 6 rats anesthetized with halothane and mechanically ventilated. Reperfusion was monitored for 1 hour. Three rats underwent sham operation. Brains were removed 24 hours after occlusion and processed for histology. Results-In control conditions, the velocity of fluorescent erythrocytes through capillaries was 0.51Ϯ0.19 mm/s (meanϮSD), and the diameter of the arterioles studied was 33Ϯ12 m. Under ischemia, erythrocyte velocity through capillaries was significantly decreased to 0.33Ϯ0.14 mm/s, while arteriole diameter did not change significantly. During spontaneous peri-infarct depolarizations, arteriole diameter was significantly increased (119Ϯ23% of baseline), while capillary erythrocyte velocity was further decreased by 14Ϯ34%. The direction of arteriolar blood flow episodically and transiently reversed during approximately half of the peri-infarct depolarizations. The decrease in capillary erythrocyte velocity was more pronounced (23Ϯ37%) in these cases. After reperfusion, the microcirculatory variables rapidly returned to baseline. All rats in the ischemic group had infarcts 24 hours after occlusion. Conclusions-Peri-infarct depolarization has an adverse influence on penumbral microcirculation, reducing capillary perfusion by erythrocytes, despite dilatation of arterioles. These findings suggest that a steal phenomenon contributes to the deleterious effect of these depolarizations.