05 October 2009

Leukocyte Accumulation in Venules following Stroke

Dr. Leslie Ritter’s article “Leukocyte Accumulation and Hemodynamic Changes in the Cerebral Microcirculation During Early Reperfusion After Stroke” addresses the fact that leukocytes play a major role in reperfusion injury following an ischemic stroke. The MCAO-R model was used and is an appropriate method because it simulates the majority of human ischemic strokes. This model along with the use of fluorescence microscopy allowed the researchers to observe the patterns of leukocyte accumulation and the hemodynamic changes in the cerebral microcirculation. This study shows how the leukocyte response, which is a component of the inflammatory cascade, is initiated following cerebral ischemia and reperfusion.

The article describes two important results found from the experiments. First of all, the researchers found that 2 hours of middle cerebral artery occlusion (MCAO) followed by 1 hour of reperfusion leads to significant leukocyte rolling and adhesion to cerebral venules. In the arterioles and capillaries, however, leukocyte rolling and adhesion increased only slightly compared to the control group but was not significant. Why do the white blood cells adhere more in the venules compared to other parts of the cerebral microcirculation? I am curious as to why there was a significant increase in leukocyte accumulation in the venules but not in the arterioles and capillaries. The other important result I wanted to mention is that the researchers found the shear rate was significantly reduced in venules following early reperfusion after MCAO. Did the leukocyte accumulation in the venules lead to a decrease in the shear rate? If not, what other factors might have caused this decrease?

Reference: http://stroke.ahajournals.org/cgi/reprint/31/5/1153

1 comment:

  1. Hi again Dana!
    Leukocytes adhere to venules for several reasons. First, during ischemia, these vessels preferentially express adhesion molecules (eg, ICAM-1) that promote leukocyte adhesion. Neither arterioles nor capillaries seem to express these molecules to any great extent. Second, venules have a lower blood flow (anlagous to shear rate) than arteries, providing the opportunity for leukocytes to roll and then adhere. In contrast to the heart, leukocytes dont plug in capillaries in the brain to a great extent, probably because the brain capillaries are several microns bigger than in the heart, and leukocytes, even stiff, activated ones, can deform enough to get through the capillary system.

    As to the shear rate question you had, shear rate is lower after reperfusion to begin with due to endothelial cell damage, but in turn, thelower shear rate promotes ahdesion, and if this adhesion actually is great enough to impede flow, then shear rate (blood flow) will decrease further. Sort of circular problem. LR

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