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Neuronal Serpina3n is an endogenous protector against blood brain barrier damage following cerebral ischemic stroke
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Li, Fengshi, Zhang, Yueman, Li, Ruqi, Li, Yan, Ding, Shenghao, Zhou, Jianpo, Huang, Tianchen, Chen, Chen, Lu, Bingwei, Yu, Weifeng, Boltze, Johannes, Li, Peiying and Wan, Jieqing (2023) Neuronal Serpina3n is an endogenous protector against blood brain barrier damage following cerebral ischemic stroke. Journal of Cerebral Blood Flow & Metabolism, 43 (2). pp. 241-257. doi:10.1177/0271678X221113897 ISSN 0271-678X.
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WRAP-Neuronal-Serpina3n-is-an-endogenous-protector-against-blood-brain-barrier-damage-following-cerebral-ischemic-stroke-Boltze-22.pdf - Accepted Version - Requires a PDF viewer. Download (15Mb) | Preview |
Official URL: https://doi.org/10.1177/0271678X221113897
Abstract
Ischemic stroke results in blood-brain barrier (BBB) disruption, during which the reciprocal interaction between ischemic neurons and components of the BBB appears to play a critical role. However, the underlying mechanisms for BBB protection remain largely unknown. In this study, we found that Serpina3n, a serine protease inhibitor, was significantly upregulated in the ischemic brain, predominantly in ischemic neurons from 6 hours to 3 days after stroke. Using neuron-specific adeno-associated virus (AAV), intranasal delivery of recombinant protein, and immune-deficient Rag1-/- mice, we demonstrated that Serpina3n attenuated BBB disruption and immune cell infiltration following stroke by inhibiting the activity of granzyme B (GZMB) and neutrophil elastase (NE) secreted by T cells and neutrophils. Furthermore, we found that intranasal delivery of rSerpina3n significantly attenuated the neurologic deficits after stroke. In conclusion, Serpina3n is a novel ischemic neuron-derived proteinase inhibitor that counterbalances BBB disruption induced by peripheral T cell and neutrophil infiltration after ischemic stroke. These findings reveal a novel endogenous protective mechanism against BBB damage with Serpina3n being a potential therapeutic target in ischemic stroke.
| Item Type: | Journal Article | ||||||||||||||||||||||||||||||||||||||||||
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| Subjects: | Q Science > QP Physiology R Medicine > RC Internal medicine |
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| Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||||||||||||||||||||||||||||||||||||||||
| Library of Congress Subject Headings (LCSH): | Cerebral ischemia, Cerebral ischemia -- Treatment , Blood-brain barrier, Serine proteinases -- Inhibitors, Leucocyte elastase | ||||||||||||||||||||||||||||||||||||||||||
| Journal or Publication Title: | Journal of Cerebral Blood Flow & Metabolism | ||||||||||||||||||||||||||||||||||||||||||
| Publisher: | Sage Publications Ltd. | ||||||||||||||||||||||||||||||||||||||||||
| ISSN: | 0271-678X | ||||||||||||||||||||||||||||||||||||||||||
| Official Date: | February 2023 | ||||||||||||||||||||||||||||||||||||||||||
| Dates: |
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| Volume: | 43 | ||||||||||||||||||||||||||||||||||||||||||
| Number: | 2 | ||||||||||||||||||||||||||||||||||||||||||
| Page Range: | pp. 241-257 | ||||||||||||||||||||||||||||||||||||||||||
| DOI: | 10.1177/0271678X221113897 | ||||||||||||||||||||||||||||||||||||||||||
| Status: | Peer Reviewed | ||||||||||||||||||||||||||||||||||||||||||
| Publication Status: | Published | ||||||||||||||||||||||||||||||||||||||||||
| Reuse Statement (publisher, data, author rights): | Li, Fengshi, Zhang, Yueman, Li, Ruqi, Li, Yan, Ding, Shenghao, Zhou, Jianpo, Huang, Tianchen, Chen, Chen, Lu, Bingwei, Yu, Weifeng, Boltze, Johannes, Li, Peiying and Wan, Jieqing (2023) Neuronal Serpina3n is an endogenous protector against blood brain barrier damage following cerebral ischemic stroke. Journal of Cerebral Blood Flow & Metabolism, 43 (2). pp. 241-257 Copyright © 2023 by International Society for Cerebral Blood Flow and Metabolism. Reprinted by permission of SAGE Publications. https://doi.org/10.1177/0271678X221113897 | ||||||||||||||||||||||||||||||||||||||||||
| Access rights to Published version: | Restricted or Subscription Access | ||||||||||||||||||||||||||||||||||||||||||
| Date of first compliant deposit: | 11 July 2022 | ||||||||||||||||||||||||||||||||||||||||||
| Date of first compliant Open Access: | 11 July 2022 | ||||||||||||||||||||||||||||||||||||||||||
| RIOXX Funder/Project Grant: |
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