In the new issue of Circulation Research ( 3), we learn that the complement system activated through exosomal signaling may also play a critical role after ischemic stroke. While the initial management of stroke has understandably focused on clotting as manifest in the 1996 FDA approval of tissue plasminogen activator (tPA), often known as a “clot-busting” agent, there has been increasing recognition that other factors including inflammation are important determinants of outcome. Stroke remains one of the leading causes of disability and death worldwide ( 2) and is predominantly due to thromboembolic occlusion of a major artery feeding the brain. It has long been recognized that many diseases are due to the two deadly “C’s” of either the clotting or complement systems ( 1) and stroke is a prime example. Received: 14 October 2021 Accepted: 08 November 2021 Published: 30 December 2021. Circulating Pro-Inflammatory Exosomes Worsen Stroke Outcomes in Aging. Email: on: Zhang H, Lin S, McElroy CL, et al. Cardiovascular Research Center, Division of Cardiology, Corrigan Minehan Heart Center, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.

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