Novel therapeutic strategies targeting innate immune responses and early inflammation after stroke
Abstract
Post‐ischemic inflammation is an essential step in the progression of ischemic stroke. This review focuses on the function of infiltrating immune cells, macrophages, and T cells, in ischemic brain injury. The brain is a sterile organ; however, the activation of Toll‐like receptor (TLR) 2 and TLR 4 is pivotal in the beginning of post‐ischemic inflammation. Some endogenous TLR ligands are released from injured brain cells, including high mobility group box 1 and peroxiredoxin family proteins, and activate the infiltrating macrophages and induce the expression of inflammatory cytokines. Following this step, T cells also infiltrate into the ischemic brain and mediate post‐ischemic inflammation in the delayed phase. Various cytokines from helper T cells and γδT cells function as neurotoxic (IL‐23/IL‐17, IFN‐γ) or neuroprotective (IL‐10, IL‐4) mediators. Novel neuroprotective strategies should therefore be developed through more detailed understanding of this process and the regulation of post‐ischemic inflammation.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
CXCL8 and IL-23 are associated with pathological neuroinflammation.
“both of these cytokines are associated with pathological neuroinflammation58–60”
From Leveraging Prior Knowledge of Endocrine Immune Regulation in the Therapeutically-relevant Phenotyping of Women with Chronic Fatigue Syndrome (2019) · cites this paper as [58]
Cites
Circulating mitochondrial DAMPs cause inflammatory responses to injury
Zhang, Q., Raoof, M., Chen, Y., Sumi, Y., Sursal, T., Junger, W., Brohi, K., Itagaki, K., & Hauser, C. J. (2010) · Nature · doi:10.1038/nature08780 · Cited by 3,812 · see citing works
Sterile inflammation: sensing and reacting to damage
Chen, G. Y., & Nuñez, G. (2010) · Nature Reviews Immunology · doi:10.1038/nri2873 · Cited by 3,051 · see citing works
Cua, D. J., Sherlock, J., Chen, Y., Murphy, C. A., Joyce, B., Seymour, B., Lucian, L., To, W., Kwan, S., Churakova, T., et al. (2003) · Nature · doi:10.1038/nature01355 · Cited by 2,906 · see citing works
Neurovascular regulation in the normal brain and in Alzheimer's disease
Iadecola, C. (2004) · Nature Reviews Neuroscience · doi:10.1038/nrn1387 · Cited by 2,213 · see citing works
The Science of Stroke: Mechanisms in Search of Treatments
Moskowitz, M. A., Lo, E. H., & Iadecola, C. (2010) · Neuron · doi:10.1016/j.neuron.2010.07.002 · Cited by 1,930 · see citing works
Kebir, H., Kreymborg, K., Ifergan, I., Dodelet-Devillers, A., Cayrol, R., Bernard, M., Giuliani, F., Arbour, N., Becher, B., & Prat, A. (2007) · Nature Medicine · doi:10.1038/nm1651 · Cited by 1,759 · see citing works
T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines
Fossiez, F., Djossou, O., Chomarat, P., Flores-Romo, L., Ait-Yahia, S., Maat, C., Pin, J. J., Garrone, P., Garcia, E., Saeland, S., et al. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.183.6.2593 · Cited by 1,526 · cited 1× · see citing works
“IL-17 has been reported to promote the expression of inflammatory cytokines and chemokines from macrophages (Fossiez et al. 1996).”
Stewart, C. R., Stuart, L. M., Wilkinson, K., van Gils, J. M., Deng, J., Halle, A., Rayner, K. J., Boyer, L., Zhong, R., Frazier, W. A., et al. (2010) · Nature Immunology · doi:10.1038/ni.1836 · Cited by 1,513 · see citing works
Reboldi, A., Coisne, C., Baumjohann, D., Benvenuto, F., Bottinelli, D., Lira, S., Uccelli, A., Lanzavecchia, A., Engelhardt, B., & Sallusto, F. (2009) · Nature Immunology · doi:10.1038/ni.1716 · Cited by 1,206 · see citing works
Chen, C.-J., Kono, H., Golenbock, D., Reed, G., Akira, S., & Rock, K. L. (2007) · Nature Medicine · doi:10.1038/nm1603 · Cited by 876 · see citing works
Regulation of innate immune responses in the brain
Rivest, S. (2009) · Nature Reviews Immunology · doi:10.1038/nri2565 · Cited by 843 · see citing works
The many faces of tumor necrosis factor in stroke
Hallenbeck, J. M. (2002) · Nature Medicine · doi:10.1038/nm1202-1363 · Cited by 367 · see citing works
Jung, J. E., Kim, G. S., & Chan, P. H. (2011) · Stroke · doi:10.1161/strokeaha.111.626648 · Cited by 127 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Kawabori, M., Kacimi, R., Kauppinen, T., Calosing, C., Kim, J. Y., Hsieh, C. L., Nakamura, M. C., & Yenari, M. A. (2015) · The Journal of Neuroscience · doi:10.1523/jneurosci.2620-14.2015 · Cited by 375 · see citing works
Darsalia, V., Hua, S., Larsson, M., Mallard, C., Nathanson, D., Nyström, T., Sjöholm, Å., Johansson, M. E., & Patrone, C. (2014) · PLoS ONE · doi:10.1371/journal.pone.0103114 · Cited by 92 · see citing works
Ischemia/reperfusion induces interferon stimulated gene expression in microglia
McDonough, A., Lee, R. V., Noor, S., Lee, C., Le, T., Iorga, M., Phillips, J. L. H., Murphy, S., Möller, T., & Weinstein, J. R. (2017) · The Journal of Neuroscience · doi:10.1523/jneurosci.0725-17.2017 · Cited by 71 · see citing works
Medvedeva, E. V., Dmitrieva, V. G., Povarova, O. V., Limborska, S. A., Skvortsova, V. I., Myasoedov, N. F., & Dergunova, L. V. (2014) · BMC Genomics · doi:10.1186/1471-2164-15-228 · Cited by 33 · see citing works
Morris, M. C., Cooney, K. E., Sedghamiz, H., Abreu, M., Collado, F., Balbin, E. G., Craddock, T. J. A., Klimas, N. G., Broderick, G., & Fletcher, M. A. (2019) · Clinical Therapeutics · doi:10.1016/j.clinthera.2019.03.002 · Cited by 14 · see citing works
- Authors
- Shichita, T., Ago, T., Kamouchi, M., Kitazono, T., Yoshimura, A., & Ooboshi, H.
- Affiliations
- Kyushu University (JP)
- Keio University (JP)
- Fukuoka Dental College Medical and Dental Hospital (JP)
- Corresponding author
- Ooboshi, Hiroaki
- ORCID
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2012-10-11
- Volume
- 123
- Issue
- s2
- Pages
- 29-38
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2138028824
- Cited by
- 136
- References
- 13
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 10 · 2023: 3 · 2022: 7 · 2021: 5 · 2020: 10 · 2019: 12 · 2018: 9 · 2017: 12 · 2016: 16 · 2015: 17 · 2014: 22 · 2013: 8 · 2012: 1
- FWCI
- 1.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Core Research for Evolutional Science and Technology
- Precursory Research for Embryonic Science and Technology
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Health Sciences › Medicine › Neurology › Intracerebral and Subarachnoid Hemorrhage Research
- Keywords
- ischemic stroke, post-ischemic inflammation, innate immune response, TLR2, TLR4, macrophages, T cells, γδ T cells, high mobility group box 1, peroxiredoxin, inflammatory cytokines, neuroprotection, neuroinflammation
- MeSH terms
- Animals, Humans, Immunity, Innate, Inflammation, Cytokines, Neuroprotective Agents, Stroke, Toll-Like Receptors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
