Leukocyte-endothelium interactions in pial venules during the early and late reperfusion period after global cerebral ischemia in gerbils

The contribution of leukocytes to secondary blain damage after cerebral isc hemia is still under discussion. The purpose of the present study was to ex amine the pial microcirculation after global cerebral ischemia while focusi ng on leukocyte-endothelium interactions during the early and late reperfus ion period of up to 4 days. A dosed cranial window technique that leaves th e dura mater intact was used. Global cerebral ischemia of 15 minutes' durat ion was induced in male Mongolian gerbils (n = 91). Pial microcirculation w as observed by intravital fluorescence microscopy. Leukocyte-endothelium in teractions (LEIs) in pial venules, vessel diameters, capillary density, and regional microvascular blood flow measured by laser Doppler flowmetry were quantified during 3 hours of reperfusion and in intervals up to 4 days aft er ischemia. Within 3 hours of reperfusion, the number of leukocytes (cells /100 mu m x minute) rolling along or adhering to the venular endothelium in creased from 0.1 +/- 0.2 to 28.4 +/- 17.4 (P < 0.01 vs. control) and from 0 .2 +/- 0.2 to 4.0 +/- 3.8 (P < 0.05) respectively. There was no capillary p lugging by leukocytes; capillary density remained unchanged. In the late re perfusion period, at 7 hours after ischemia, LEIs had returned to baseline values. Furthermore, from 12 hours to 4 days after ischemia, no LEIs were o bserved. Changes in regional microvascular blood flow did not correlate wit h LEIs. Global cerebral ischemia of 15 minutes' duration induces transient LEIs that reach a maximum within 3 hours of reperfusion and return to basel ine at 7 hours after ischemia. LEIs are not related to changes in microvasc ular perfusion, which suggests mainly that the expression of adhesion recep tors is necessary to induce LEIs rather than theologic factors. Tt seems un likely that this short-lasting activation of leukocytes can play a role in the development of secondary brain damage.