{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T02:26:18Z","timestamp":1788229578900,"version":"build-2803163510"},"reference-count":40,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2021,6,22]],"date-time":"2021-06-22T00:00:00Z","timestamp":1624320000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81701170"],"award-info":[{"award-number":["81701170"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81920108017"],"award-info":[{"award-number":["81920108017"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81630028"],"award-info":[{"award-number":["81630028"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20170122"],"award-info":[{"award-number":["BK20170122"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Ischemic stroke is a life\u2010threatening disease with limited therapeutic strategies. Blood\u2010brain barrier (BBB) disruption is a critical pathological process that contributes to poor outcomes in ischemic stroke. We previously showed that the microglial inhibition of the inflammasome sensor\u00a0absent in melanoma 2 (AIM2) suppressed the inflammatory response and protected against ischemic stroke. However, whether AIM2 is involved in BBB disruption during cerebral ischemia is unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Middle cerebral artery occlusion (MCAO) and oxygen\u2010glucose deprivation\/reoxygenation (OGD\/R) were used to mimic cerebral ischemia in mice and brain microvascular\u00a0endothelial\u00a0cells (HBMECs), respectively. The infarct volume, neurological deficits, and BBB permeability were measured in mice after MCAO. Transendothelial electrical resistance (TEER) and neutrophil adhesion to the HBMEC monolayer were assessed after OGD\/R treatment. Western blot and immunofluorescence analyses were conducted to evaluate the expression of related proteins.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>AIM2 was shown to be expressed in brain endothelial cells and upregulated after ischemic stroke in the mouse brain. AIM2 deletion reduced the infarct volume, improved neurological and motor functions, and decreased BBB disruption. In vitro, OGD\/R significantly increased the protein levels of AIM2 and ICAM\u20101 and decreased those of the tight junction (TJ) proteins ZO\u20101 and occludin. AIM2\u00a0knockdown effectively protected BBB integrity by promoting the expression of TJ proteins and decreasing ICAM\u20101 expression and neutrophil adhesion. Mechanistically, AIM2\u00a0knockdown reversed the OGD\/R\u2010induced increases in ICAM\u20101 expression and STAT3 phosphorylation in brain endothelial cells. Furthermore, treatment with the p\u2010STAT3 inhibitor AG490\u00a0mitigated the effect of AIM2 on BBB breakdown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings indicated that inhibiting AIM2 preserved the BBB integrity after ischemic stroke, at least partially by modulating STAT3 activation and that AIM2\u00a0may be a promising therapeutic target for cerebral ischemic stroke.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cns.13699","type":"journal-article","created":{"date-parts":[[2021,6,22]],"date-time":"2021-06-22T05:21:07Z","timestamp":1624339267000},"page":"1224-1237","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["AIM2 deletion enhances blood\u2010brain barrier integrity in experimental ischemic 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Institute of Brain Science Nanjing University Nanjing China"},{"name":"Department of Neurology Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University Nanjing China"},{"name":"Department of Neurology Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine Nanjing China"},{"name":"Jiangsu Key Laboratory for Molecular Medicine Medical School of Nanjing University Nanjing China"},{"name":"Jiangsu Province Stroke Center for Diagnosis and Therapy Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng\u2010nan","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Neurology Drum Tower Hospital Medical School and The State Key Laboratory of Pharmaceutical Biotechnology Institute of Brain Science Nanjing University Nanjing 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