The DOI matches its Crossref record; 61 of the 61 references it cites were found in a registry or an index.
Neutrophil extracellular traps regulate ischemic stroke brain injury
Open accessAbstract
Ischemic stroke prompts a strong inflammatory response, which is associated with exacerbated outcomes. In this study, we investigated mechanistic regulators of neutrophil extracellular trap (NET) formation in stroke and whether they contribute to stroke outcomes. NET-forming neutrophils were found throughout brain tissue of ischemic stroke patients, and elevated plasma NET biomarkers correlated with worse stroke outcomes. Additionally, we observed increased plasma and platelet surface-expressed high-mobility group box 1 (HMGB1) in stroke patients. Mechanistically, platelets were identified as the critical source of HMGB1 that caused NETs in the acute phase of stroke. Depletion of platelets or platelet-specific knockout of HMGB1 significantly reduced plasma HMGB1 and NET levels after stroke, and greatly improved stroke outcomes. We subsequently investigated the therapeutic potential of neonatal NET-inhibitory factor (nNIF) in stroke. Mice treated with nNIF had smaller brain infarcts, improved long-term neurological and motor function, and enhanced survival after stroke. nNIF specifically blocked NET formation without affecting neutrophil recruitment after stroke. Importantly, nNIF also improved stroke outcomes in diabetic and aged mice and was still effective when given 1 hour after stroke onset. These results support a pathological role for NETs in ischemic stroke and warrant further investigation of nNIF for stroke therapy.
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Heart Disease and Stroke Statistics—2021 Update: A Report From the American Heart Association
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Of Mice and Not Men: Differences between Mouse and Human Immunology
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von Brühl, M.-L., Stark, K., Steinhart, A., Chandraratne, S., Konrad, I., Lorenz, M., Khandoga, A., Tirniceriu, A., Coletti, R., Köllnberger, M., et al. (2012) · Journal of Experimental Medicine · doi:10.1084/jem.20112322 · Cited by 1,823
PAD4 is essential for antibacterial innate immunity mediated by neutrophil extracellular traps
Li, P., Li, M., Lindberg, M. R., Kennett, M. J., Xiong, N., & Wang, Y. (2010) · Journal of Experimental Medicine · doi:10.1084/jem.20100239 · Cited by 1,495
Impairment of neutrophil extracellular trap degradation is associated with lupus nephritis
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Middleton, E. A., He, X.-Y., Denorme, F., Campbell, R. A., Ng, D., Salvatore, S. P., Mostyka, M., Baxter-Stoltzfus, A., Borczuk, A. C., Loda, M., et al. (2020) · Blood · doi:10.1182/blood.2020007008 · Cited by 1,460
Self-citationUpdate of the Stroke Therapy Academic Industry Roundtable Preclinical Recommendations
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An emerging role for neutrophil extracellular traps in noninfectious disease
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Reciprocal coupling of coagulation and innate immunity via neutrophil serine proteases
Massberg, S., Grahl, L., von Bruehl, M.-L., Manukyan, D., Pfeiler, S., Goosmann, C., Brinkmann, V., Lorenz, M., Bidzhekov, K., Khandagale, A. B., et al. (2010) · Nature Medicine · doi:10.1038/nm.2184 · Cited by 1,206
Interplay between inflammation and thrombosis in cardiovascular pathology
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Cited by
Systemic inflammation after stroke: implications for post‐stroke comorbidities
Simats, A., & Liesz, A. (2022) · EMBO Molecular Medicine · doi:10.15252/emmm.202216269 · Cited by 276
Zhang, L., Liu, Y., Wang, K., Ou, X., Zhou, J., Zhang, H., Huang, M., Du, Z., & Qiang, S. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-04573-x · Cited by 18
Metadata
- Authors
- Denorme, F., Portier, I., Rustad, J. L., Cody, M. J., de Araujo, C. V., Hoki, C., Alexander, M. D., Grandhi, R., Dyer, M. R., Neal, M. D., Majersik, J. J., Yost, C. C., & Campbell, R. A.
- Venue
- Journal of Clinical Investigation
- Published
- 2022-05-16
- Volume
- 132
- Issue
- 10
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- OpenAlex
- W4220933397
- Cited by
- 391
- References
- 61
- FWCI
- 21.94
- Type
- journal article
- Language
- en
- Open access
- gold
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- Denorme, F., Portier, I., Rustad, J. L., Cody, M. J., de Araujo, C. V., Hoki, C., Alexander, M. D., Grandhi, R., Dyer, M. R., Neal, M. D., Majersik, J. J., Yost, C. C., & Campbell, R. A. (2022). Neutrophil extracellular traps regulate ischemic stroke brain injury. Journal of Clinical Investigation. https://doi.org/10.1172/jci154225
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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