Post-stroke inflammation and brain injury

Identify candidate pathways

Although inflammation after ischemic stroke is a well-described phenomenon and hypothesized to play a key role in secondary injury, the underlying mechanisms are not well understood. We have identified soluble ST2 as an inflammatory biomarker that is elevated following acute ischemic stroke. Our studies have highlighted that soluble ST2 predicts functional outcome, mortality and risk of hemorrhagic transformation, and these associations are independent from traditional clinical risk factors.

Soluble ST2 is a decoy receptor in the IL-33/ST2 pathway, which is a member of the Toll-like/Interleukin-1 receptor superfamily.  Prior immunological studies of ST2 have shown that the soluble form antagonizes normal IL-33 signaling and alters the balance between pro-inflammatory versus reparative immune responses. Our laboratory is investigating how soluble ST2 may influence post-stroke innate inflammatory responses regulate the switch towards tissue repair.

Related Publications:

Association of Soluble ST2 With Functional Outcome, Perihematomal Edema, and Immune Response After Intraparenchymal Hemorrhage
Bevers M, Booraem C, Li K, Sreekrishnan A, Sastre C, Falcone GJ, Sheth KN, Sansing LH, Kimberly WT. Association of Soluble ST2 With Functional Outcome, Perihematomal Edema, and Immune Response After Intraparenchymal Hemorrhage. Neurology, in press, (2022).
Early Brain Injury and Soluble ST2 After Nontraumatic Subarachnoid Hemorrhage
Schleicher RL, Bevers MB, Rubin DB, Koch MJ, Bache S, Lissak IA, Patel AB, Rosenthal ES, Møller K, Kimberly WT. Stroke, 52(8):e494-e496, (2021). view PDF
Soluble ST2 is associated with new epileptiform abnormalities following nontraumatic subarachnoid hemorrhage
Lissak IA, Sahar ZF, Westover BM, Schleicher RL, Kim JA, Leslie-Mazwi T, Stapleton CJ, Patel AB, Kimberly WT and Rosenthal ES. Stroke, 51:1128-1134 (2020).
Soluble ST2 links inflammation to outcome after subarachnoid hemorrhage
Bevers MB, Wolcott Z, Bache S, Hansen C, Sastre C, Mylvaganam R, Koch MJ, Patel AB, Møller K and Kimberly WT. Ann Neurol, 83:384-394 (2019). view PDF
Soluble ST2 predicts outcome and hemorrhagic transformation after acute stroke
Wolcott Z, Batra A, Bevers MB, Sastre C, Khoury J, Sperling M, Meyer BC, Walsh KB, Adeoye O, Broderick JP, and Kimberly WT. Ann Clin Transl Neurol, 4:553-563 (2017). view PDF