Microvascular Responses to Ischemic Stroke following Splenectomy

Abstract

Splenectomy is known to protect the brain against the tissue injury that results from ischemia and reperfusion (I/R). The mechanisms that underlie this neuroprotective effect of splenectomy remain poorly understood. An early response to brain I/R is the recruitment of inflammatory cells and platelets into the cerebral microvasculature. The objective of this study was to determine if splenectomy alters the recruitment of adherent leukocytes and platelets in cerebral microvessels in the early phase (24 hr) of reperfusion following ischemic stroke. Wild type C57Bl/6 mice underwent splenectomy or sham splenectomy two weeks prior to 45 min middle cerebral artery occlusion (MCAO) followed by 24 h of reperfusion. After 24 h of reperfusion, intravital fluorescence video microscopy was used to monitor and quantify the adhesion of leukocytes (rhodamine‐G6 labeled) and platelets (CFSE‐labeled) in cerebral venules. Infarct volume and peripheral blood counts were also measured. Splenectomy attenuates the recruitment of adherent platelets and leukocytes in the cerebral microvasculature and reduces infarct volume. The increased blood platelet count observed following MCAO was reduced to control levels in splenectomized animals. Peripheral leukocyte count did not differ between the splenectomized and sham splenectomized mice. These results implicate the spleen in I/R‐induced brain inflammation, thrombogenesis, and tissue necrosis as early as 24 h after reperfusion (Supported by a Malcolm Feist Postdoctoral Fellowship)