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DOI | 10.1073/pnas.2021915118 |
Blood-brain barrier opening by intracarotid artery hyperosmolar mannitol induces sterile inflammatory and innate immune responses | |
Burks S.R.; Kersch C.N.; Witko J.A.; Pagel M.A.; Sundby M.; Muldoon L.L.; Neuwelt E.A.; Frank J.A. | |
发表日期 | 2021 |
ISSN | 00278424 |
卷号 | 118期号:18 |
英文摘要 | Intracarotid arterial hyperosmolar mannitol (ICAHM) blood-brain barrier disruption (BBBD) is effective and safe for delivery of therapeutics for central nervous system malignancies. ICAHM osmotically alters endothelial cells and tight junction integrity to achieve BBBD. However, occurrence of neuroinflammation following hemispheric BBBD by ICAHM remains unknown. Temporal proteomic changes in rat brains following ICAHM included increased damage-associated molecular patterns, cytokines, chemokines, trophic factors, and cell adhesion molecules, indicative of a sterile inflammatory response (SIR). Proteomic changes occurred within 5 min of ICAHM infusion and returned to baseline by 96 h. Transcriptomic analyses following ICAHM BBBD further supported an SIR. Immunohistochemistry revealed activated astrocytes, microglia, and macrophages. Moreover, proinflammatory proteins were elevated in serum, and proteomic and histological findings from the contralateral hemisphere demonstrated a less pronounced SIR, suggesting neuroinflammation beyond regions of ICAHM infusion. Collectively, these results demonstrate ICAHM induces a transient SIR that could potentially be harnessed for neuroimmunomodulation. © 2021 National Academy of Sciences. All rights reserved. |
英文关键词 | Blood-brain barrier; Hyperosmolar mannitol; Neuroinflammation; Sterile inflammation |
语种 | 英语 |
来源期刊 | Proceedings of the National Academy of Sciences of the United States of America
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文献类型 | 期刊论文 |
条目标识符 | http://gcip.llas.ac.cn/handle/2XKMVOVA/179702 |
作者单位 | Frank Laboratory, Radiology and Imaging Sciences, NIH Clinical Center, Bethesda, MD 20895, United States; Department of Neurology, Oregon Health & Science University, Portland, OR 97239, United States; Department of Neurological Surgery, Oregon Health & Science University, Portland, OR 97239, United States; Portland Veterans Affairs Medical Center, Portland, OR 97239, United States; National Institute of Biomedical Imaging and Bioengineering, Bethesda, MD 20895, United States |
推荐引用方式 GB/T 7714 | Burks S.R.,Kersch C.N.,Witko J.A.,et al. Blood-brain barrier opening by intracarotid artery hyperosmolar mannitol induces sterile inflammatory and innate immune responses[J],2021,118(18). |
APA | Burks S.R..,Kersch C.N..,Witko J.A..,Pagel M.A..,Sundby M..,...&Frank J.A..(2021).Blood-brain barrier opening by intracarotid artery hyperosmolar mannitol induces sterile inflammatory and innate immune responses.Proceedings of the National Academy of Sciences of the United States of America,118(18). |
MLA | Burks S.R.,et al."Blood-brain barrier opening by intracarotid artery hyperosmolar mannitol induces sterile inflammatory and innate immune responses".Proceedings of the National Academy of Sciences of the United States of America 118.18(2021). |
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