Ischemic stroke‐induced increases in circulating microparticles promote leukocyte adhesion in intact microvessels (672.3)

Abstract

Studies in both stroke patients and experimental animals indicate an association between ischemic stroke and post stroke peripheral inflammation, but the mechanisms are poorly understood. Our ongoing study indicated that circulating microparticles (MPs), the small vesicles released from the cell membrane upon activation, were significantly elevated in both patients and animals with diabetes, and increased circulating MPs with phosphatidylserine (PS) exposure on their outer membrane played important roles in the development of diabetes‐associated microvascular complications. The objective of this study was to investigate whether local ischemic stroke produced increased circulating MPs and determine their impact on post stroke‐associated peripheral vascular inflammation. Acute cerebral ischemia was induced by occlusion of the right middle cerebral artery (MCAO) in 3‐4 month old rats using an autologous blood clot. Functional assessment, lesion volume, and hemispheric swelling were evaluated at 24h after MCAO. Plasma MPs 24h after stroke induction were quantified and characterized using flow cytometry. The number of PS exposed MPs in stroke plasma, identified by Annexin V binding, significantly increased from 5.0 x 103 (normal rats) to 30 x 103 per µl. Antibodies directly against cell specific antigens were used to differentiate the MP cell origin. Results showed that 67% of the increased stroke plasma MPs were derived from platelets. Perfusion of individually cannulated normal rat mesenteric microvessels with isolated stroke MPs for 30 min followed by 10 min of resumed blood flow induced a 4‐fold increase in leukocyte adhesion compared to baseline. These results indicate that stroke‐induced increased circulating MPs serve as mediators capable of disseminating local inflammation to remote vasculatures, and therefore, promoting post stroke systemic complications.Grant Funding Source: Supported by HL56237, DK097391, NS061954