{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T23:34:55Z","timestamp":1789601695550,"version":"build-2803163510"},"reference-count":23,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,4,13]],"date-time":"2020-04-13T00:00:00Z","timestamp":1586736000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of Chongqing","doi-asserted-by":"crossref","award":["cstc2016jcyjA0012"],"award-info":[{"award-number":["cstc2016jcyjA0012"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Excessive neuroinflammation aggravates the brain injury caused by intracerebral hemorrhage (ICH), while the upstream mechanisms that initiate neuroinflammation remain unclear. Toll\u2010like receptor 4 (TLR4) signaling is important to trigger inflammatory responses in ICH, and cold\u2010inducible RNA\u2010binding protein (CIRP) has been shown as a novel ligand of TLR4 by recent studies. However, whether the CIRP could trigger the neuroinflammation via activating TLR4 signaling in ICH still needs to be investigated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Human serum CIRP levels were measured using the ELISA kits. Western blot, FJB staining, brain water content, and neurological deficit scores were used to investigate the roles of CIRP in brain injury caused by ICH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Result<\/jats:title>\n                    <jats:p>\n                      First, we found increased CIRP levels in the blood of patients with ICH when compared to the control individuals, and the ICH patients with mRS\u00a0&gt;\u00a02 have higher serum CIRP levels in contrast to those with mRS\u00a0\u2264\u00a02. In the ICH mice, we also found that brain CIRP protein and mRNA levels were also increased after ICH. Furthermore, using the CIRP\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice, we found that CIRP\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice had less brain damages showing in less FJB\n                      <jats:sup>+<\/jats:sup>\n                      cells, reduced brain water content (BWC) and lower neurological deficit scores (NDS) compared to that in WT mice after ICH. Cytokines including IL\u20106, TNF\u2010\u03b1, and IL\u20101\u03b2 from CIRP\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice were attenuated after ICH. CIRP\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice also exhibited reduced TLR4 expression which was accompanied by the decreased activity of NF\u2010\u03baB. This suggests that TLR4 signaling might be involved in CIRP\u2010mediated inflammatory injury possibly via NF\u2010\u03baB activation after ICH.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings suggest that CIRP may activate TLR4 signaling, and further inducing NF\u2010\u03baB activation to increase the expression levels of cytokines and aggravate inflammatory injury in ICH. Targeting CIRP may be a promising strategy for ICH treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.1618","type":"journal-article","created":{"date-parts":[[2020,4,13]],"date-time":"2020-04-13T22:23:36Z","timestamp":1586816616000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Cold\u2010inducible RNA\u2010binding protein contributes to intracerebral hemorrhage\u2010induced brain injury via TLR4 signaling"],"prefix":"10.1002","volume":"10","author":[{"given":"Kai","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Neurology Xinqiao Hospital &amp; The Second Affiliated Hospital The Army (Third Military) Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengtao","family":"Cui","sequence":"additional","affiliation":[{"name":"Graduate School The Army (Third Military) Medical University Chongqing 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Xinqiao Hospital &amp; The Second Affiliated Hospital The Army (Third Military) Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zili","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Neurology Xinqiao Hospital &amp; The Second Affiliated Hospital The Army (Third Military) Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0717-5247","authenticated-orcid":false,"given":"Yu","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Neurology Xinqiao Hospital &amp; The Second Affiliated Hospital The Army (Third Military) Medical University Chongqing 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