Cited by 857Neuroinflammation and Neurodegeneration MechanismsAcute Ischemic Stroke ManagementIntracerebral and Subarachnoid Hemorrhage Research

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Immune responses to stroke: mechanisms, modulation, and therapeutic potential.

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Iadecola, Costantino, Buckwalter, Marion S., Anrather, Josef·2020·Journal of Clinical Investigation

DOI 10.1172/jci135530PMC PMC7260029

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Abstract

Stroke is the second leading cause of death worldwide and a leading cause of disability. Most strokes are caused by occlusion of a major cerebral artery, and substantial advances have been made in elucidating how ischemia damages the brain. In particular, increasing evidence points to a double-edged role of the immune system in stroke pathophysiology. In the acute phase, innate immune cells invade brain and meninges and contribute to ischemic damage, but may also be protective. At the same time, danger signals released into the circulation by damaged brain cells lead to activation of systemic immunity, followed by profound immunodepression that promotes life-threatening infections. In the chronic phase, antigen presentation initiates an adaptive immune response targeted to the brain, which may underlie neuropsychiatric sequelae, a considerable cause of poststroke morbidity. Here, we briefly review these pathogenic processes and assess the potential therapeutic value of targeting immunity in human stroke.

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Additional file 3 of Association of admission neutrophil serine proteinases levels with the outcomes of acute ischemic stroke: a prospective cohort study
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Additional file 2 of TRIM67 alleviates cerebral ischemia‒reperfusion injury by protecting neurons and inhibiting neuroinflammation via targeting IκBα for K63-linked polyubiquitination
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Additional file 5 of CD13 facilitates immune cell migration and aggravates acute injury but promotes chronic post-stroke recovery
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Additional file 6 of Early peripheral blood gene expression associated with good and poor 90-day ischemic stroke outcomes
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Additional file 2 of Association of admission neutrophil serine proteinases levels with the outcomes of acute ischemic stroke: a prospective cohort study
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Additional file 1 of Receptor-interacting protein kinase 2 (RIPK2) profoundly contributes to post-stroke neuroinflammation and behavioral deficits with microglia as unique perpetrators
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Additional file 2 of Association between dietary inflammatory index and Stroke in the US population: evidence from NHANES 1999–2018
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Additional file 5 of Early peripheral blood gene expression associated with good and poor 90-day ischemic stroke outcomes
Amini, H., Knepp, B., Rodríguez, F., Jickling, G. C., Hull, H., Carmona-Mora, P., Bushnell, C., Ander, B. P., Sharp, F. R., & Stamova, B. S. (2024) · Figshare · doi:10.6084/m9.figshare.26563348
Additional file 3 of Early peripheral blood gene expression associated with good and poor 90-day ischemic stroke outcomes
Amini, H., Knepp, B., Rodríguez, F., Jickling, G. C., Hull, H., Carmona-Mora, P., Bushnell, C., Ander, B. P., Sharp, F. R., & Stamova, B. S. (2024) · Figshare · doi:10.6084/m9.figshare.26563342
Additional file 2 of Early peripheral blood gene expression associated with good and poor 90-day ischemic stroke outcomes
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Additional file 3 of CD13 facilitates immune cell migration and aggravates acute injury but promotes chronic post-stroke recovery
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Additional file 5 of TRIM67 alleviates cerebral ischemia‒reperfusion injury by protecting neurons and inhibiting neuroinflammation via targeting IκBα for K63-linked polyubiquitination
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Additional file 3 of TRIM67 alleviates cerebral ischemia‒reperfusion injury by protecting neurons and inhibiting neuroinflammation via targeting IκBα for K63-linked polyubiquitination
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Additional file 2 of CD13 facilitates immune cell migration and aggravates acute injury but promotes chronic post-stroke recovery
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Additional file 4 of TRIM67 alleviates cerebral ischemia‒reperfusion injury by protecting neurons and inhibiting neuroinflammation via targeting IκBα for K63-linked polyubiquitination
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Additional file 1 of CD13 facilitates immune cell migration and aggravates acute injury but promotes chronic post-stroke recovery
Nguyen, J. N., Mohan, E. C., Pandya, G., Ali, U., Tan, C., Kofler, J. K., Shapiro, L. H., Marrelli, S. P., & Chauhan, A. (2024) · Figshare · doi:10.6084/m9.figshare.26625418
Additional file 4 of Early peripheral blood gene expression associated with good and poor 90-day ischemic stroke outcomes
Amini, H., Knepp, B., Rodríguez, F., Jickling, G. C., Hull, H., Carmona-Mora, P., Bushnell, C., Ander, B. P., Sharp, F. R., & Stamova, B. S. (2024) · Figshare · doi:10.6084/m9.figshare.26563345
Additional file 6 of CD13 facilitates immune cell migration and aggravates acute injury but promotes chronic post-stroke recovery
Nguyen, J. N., Mohan, E. C., Pandya, G., Ali, U., Tan, C., Kofler, J. K., Shapiro, L. H., Marrelli, S. P., & Chauhan, A. (2024) · Figshare · doi:10.6084/m9.figshare.26625433
Additional file 1 of Association between dietary inflammatory index and Stroke in the US population: evidence from NHANES 1999–2018
Mao, Y., Weng, J., Xie, Q., Wu, L., Xuan, Y., Zhang, J., & Han, J. (2024) · Figshare · doi:10.6084/m9.figshare.24934102
Additional file 1 of Association of admission neutrophil serine proteinases levels with the outcomes of acute ischemic stroke: a prospective cohort study
Li, L., Han, Z., Wang, R., Fan, J., Zheng, Y., Huang, Y., Yang, Z., Yan, F., Liu, P., Zhao, H., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22623854
Additional file 1 of Early peripheral blood gene expression associated with good and poor 90-day ischemic stroke outcomes
Amini, H., Knepp, B., Rodríguez, F., Jickling, G. C., Hull, H., Carmona-Mora, P., Bushnell, C., Ander, B. P., Sharp, F. R., & Stamova, B. S. (2024) · Figshare · doi:10.6084/m9.figshare.26563336
Additional file 4 of CD13 facilitates immune cell migration and aggravates acute injury but promotes chronic post-stroke recovery
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Authors: Iadecola, C., Buckwalter, M. S., & Anrather, J.
Affiliations: Weill Cornell Medicine (US)
Stanford Medicine (US)
Corresponding author: Iadecola, Costantino
ORCID: Iadecola, Costantino
Buckwalter, Marion S.
Anrather, Josef
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2020-05-11
Volume: 130
Issue: 6
Pages: 2777-2788
ISSN: 0021-9738 (ISSN-L)
1558-8238
DOI: 10.1172/jci135530
PMC: PMC7260029
OpenAlex: W3022448963
Cited by: 853
References: 203
Citations by year: 2026: 151 · 2025: 171 · 2024: 175 · 2023: 167 · 2022: 128 · 2021: 49 · 2020: 10
FWCI: 8.84
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: American Heart Association (19PABHI34580007)
National Institutes of Health (NS34179, R01-NS34179)
College of Veterinary Medicine, Cornell University
National Institute of Neurological Disorders and Stroke (R01NS034179, R01NS081179, R01NS094507)
Topics: Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Health Sciences › Medicine › Clinical Neurology › Acute Ischemic Stroke Management
Health Sciences › Medicine › Clinical Neurology › Intracerebral and Subarachnoid Hemorrhage Research
Keywords: stroke, immune response, ischemic stroke, innate immunity, adaptive immunity, neuroinflammation, secondary infection, antigen presentation, neuropsychiatric sequelae, immunomodulatory therapy, cerebral ischemia
MeSH terms: Animals, Brain Ischemia, Humans, Inflammation, Stroke, Adaptive Immunity

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Immune responses to stroke: mechanisms, modulation, and therapeutic potential.

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