Leukocyte accumulation and hemodynamic changes in the cerebral microcirculation during early reperfusion after stroke

Background and Purpose-Leukocytes contribute to cerebral ischemia-reperfusi on injury. However, few experimental models examine both in vivo behavior o f leukocytes and microvascular rheology after stroke. The purpose of the pr esent study was to characterize patterns of leukocyte accumulation in the c erebral microcirculation and to examine the relationship between leukocyte accumulation and microcirculatory hemodynamics after middle cerebral artery occlusion and reperfusion (MCAO-R). Methods Male rats (250 to 350 g) were anesthetized and ventilated. Tail cat heters were inserted for measurement of arterial blood gases and administra tion of drugs. Body temperature was maintained at 37 degrees C. Animals wer e subjected to 2 hours of MCAO by the filament method. A cranial-window pre paration was performed, and the brain was superfused with warm, aerated art ificial cerebrospinal fluid. Reperfusion was initiated by withdrawing the f ilament, and the pial microcirculation was observed by use of intravital fl uorescence microscopy. Leukocyte accumulation in venules, arterioles, and c apillaries; leukocyte rolling in venules; and leukocyte venular shear rate were assessed during 1 hour of reperfusion. Results-We found significant leukocyte adhesion in cerebral venules during 1 hour of reperfusion after 2 hours of MCAO. Leukocyte trapping in capillar ies and adhesion to arterioles after MCAO-R tended to increase compared wit h controls, but the increase was not significant. We also found that shear rate was significantly reduced in venules during early reperfusion after MC AO. Conclusions-A model using the filament method of stroke and fluorescence mi croscopy was used to examine white-cell behavior and hemodynamics in the ce rebral microcirculation after MCAO-R. We observed a significant increase in leukocyte rolling and adhesion in venules and a significant decrease in bl ood shear rate in the microcirculation of the brain during early reperfusio n. Leukocytes may activate and damage the blood vessels and surrounding bra in cells, which contributes to an exaggerated inflammatory component to rep erfusion. The model described can be used to examine precisely blood cell-e ndothelium interactions and hemodynamic changes in the microcirculation dur ing postischemic reperfusion. Information from these and similar experiment s may contribute to our understanding of the early inflammatory response in the brain during reperfusion after stroke.