{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T23:34:30Z","timestamp":1789601670975,"version":"build-2803163510"},"reference-count":159,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"China Association of Chinese Medicine","award":["2023HH-012"],"award-info":[{"award-number":["2023HH-012"]}]},{"name":"Hubei Provincial Administration of Traditional Chinese Medicine","award":["ZY2025L267"],"award-info":[{"award-number":["ZY2025L267"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Cold-inducible RNA-binding protein (CIRP) is a critical molecule in the central nervous system (CNS) with functions that depend on its subcellular localization, exhibiting biphasic regulatory roles in both physiological and pathological processes. Under physiological conditions, intracellular cold-inducible RNA-binding protein (iCIRP) contributes to the maintenance of circadian rhythms by regulating the stability of core clock gene mRNAs and exerts neuroprotective effects during mild hypothermia by preserving the blood\u2013brain barrier and inhibiting apoptosis. Pathologically, extracellular cold-inducible RNA-binding protein (eCIRP) functions as a damage-associated molecular pattern (DAMP) that drives neuroinflammation and brain injury. In ischemic stroke (IS), eCIRP promotes neutrophil extracellular trap (NET) formation and increases microglial activity via the Toll-like receptor 4 (TLR4) pathway. In cerebral ischemia\u2013reperfusion (I\/R) injury, eCIRP activates oxidative stress and the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome through the TLR4 axis, exacerbating mitochondrial damage. In intracerebral hemorrhage (ICH), eCIRP further amplifies inflammation via the interleukin-6 receptor (IL-6R)\/signal transducer and activator of transcription 3 (STAT3) signaling pathway. In traumatic brain injury (TBI), eCIRP activates the endoplasmic reticulum stress pathway, intensifying apoptosis. In Alzheimer\u2019s disease (AD), eCIRP regulates tau phosphorylation and \u03b2-amyloid (A\u03b2) metabolism and may mediate the link between alcohol exposure and AD pathology. Preclinical studies indicate that serum eCIRP levels correlate with IS and ICH severity, highlighting its potential as a biomarker. This systematic review elucidates the mechanisms of CIRP in CNS diseases, providing insights for understanding and preventing conditions such as IS, cerebral I\/R injury, ICH, TBI, and AD.<\/jats:p>","DOI":"10.3390\/brainsci16020205","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T16:13:32Z","timestamp":1770653612000},"page":"205","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Role of Cold-Inducible RNA-Binding Protein (CIRP) in Neurological Disorders"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-4350-9113","authenticated-orcid":false,"given":"Xueqi","family":"Lai","sequence":"first","affiliation":[{"name":"Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0378-1119(97)00530-1","article-title":"Cloning and characterization of human CIRP (cold-inducible RNA-binding protein) cDNA and chromosomal assignment of the gene","volume":"204","author":"Nishiyama","year":"1997","journal-title":"Gene"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1083\/jcb.137.4.899","article-title":"A glycine-rich RNA-binding protein mediating cold-inducible suppression of mammalian cell growth","volume":"137","author":"Nishiyama","year":"1997","journal-title":"J. Cell Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"Fso246","DOI":"10.4155\/fsoa-2017-0077","article-title":"Recent progress in the research of cold-inducible RNA-binding protein","volume":"3","author":"Zhong","year":"2017","journal-title":"Future Sci. OA"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Zhong, P., Peng, J., Bian, Z., and Huang, H. (2021). The Role of Cold Inducible RNA-Binding Protein in Cardiac Physiology and Diseases. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.610792"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/j.bbrc.2019.05.012","article-title":"CIRP downregulation renders cardiac cells prone to apoptosis in heart failure","volume":"517","author":"Chen","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1002\/JLB.3MIR1118-443R","article-title":"Extracellular CIRP (eCIRP) and inflammation","volume":"106","author":"Aziz","year":"2019","journal-title":"J. Leukoc. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e12949","DOI":"10.1111\/sji.12949","article-title":"Cold-inducible RNA-binding protein (CIRP) in inflammatory diseases: Molecular insights of its associated signalling pathways","volume":"93","author":"Zhong","year":"2021","journal-title":"Scand. J. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1111\/jcmm.17142","article-title":"The role of Cold-Inducible RNA-binding protein in respiratory diseases","volume":"26","author":"Zhong","year":"2022","journal-title":"J. Cell. Mol. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1038\/nm.3368","article-title":"Cold-inducible RNA-binding protein (CIRP) triggers inflammatory responses in hemorrhagic shock and sepsis","volume":"19","author":"Qiang","year":"2013","journal-title":"Nat. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/cmi.2016.43","article-title":"Cold-inducible RNA-binding protein activates splenic T cells during sepsis in a TLR4-dependent manner","volume":"15","author":"Bolognese","year":"2018","journal-title":"Cell. Mol. Immunol."},{"key":"ref_11","first-page":"275","article-title":"CIRP promotes the progression of non-small cell lung cancer through activation of Wnt\/\u03b2-catenin signaling via CTNNB1","volume":"40","author":"Liao","year":"2021","journal-title":"J. Exp. Clin. Cancer Res. CR"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Han, J., Zhang, Y., Ge, P., Dakal, T.C., Wen, H., Tang, S., Luo, Y., Yang, Q., Hua, B., and Zhang, G. (2023). Exosome-derived CIRP: An amplifier of inflammatory diseases. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1066721"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1097\/SHK.0000000000000251","article-title":"Blocking cold-inducible RNA-binding protein protects liver from ischemia-reperfusion injury","volume":"43","author":"Godwin","year":"2015","journal-title":"Shock"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1016\/j.jtcvs.2018.08.100","article-title":"Cold-inducible RNA-binding protein as a novel target to alleviate blood-brain barrier damage induced by cardiopulmonary bypass","volume":"157","author":"Liu","year":"2019","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.brainres.2010.08.048","article-title":"Moderate low temperature preserves the stemness of neural stem cells and suppresses apoptosis of the cells via activation of the cold-inducible RNA binding protein","volume":"1358","author":"Saito","year":"2010","journal-title":"Brain Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"518","DOI":"10.7150\/ijbs.17800","article-title":"Cold Inducible RNA Binding Protein Is Involved in Chronic Hypoxia Induced Neuron Apoptosis by Down-Regulating HIF-1\u03b1 Expression and Regulated By microRNA-23a","volume":"13","author":"Chen","year":"2017","journal-title":"Int. J. Biol. Sci."},{"key":"ref_17","first-page":"1515","article-title":"Association between CIRP expression and hypoxic-ischemic brain injury in neonatal rats","volume":"18","author":"Chen","year":"2019","journal-title":"Exp. Ther. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.bbamcr.2006.02.007","article-title":"Cirp protects against tumor necrosis factor-alpha-induced apoptosis via activation of extracellular signal-regulated kinase","volume":"1763","author":"Sakurai","year":"2006","journal-title":"Biochim. et Biophys. Acta"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"771","DOI":"10.4103\/1673-5374.182704","article-title":"Neuroprotective effects of cold-inducible RNA-binding protein during mild hypothermia on traumatic brain injury","volume":"11","author":"Wang","year":"2016","journal-title":"Neural Regen. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.brainres.2014.11.061","article-title":"Cloning, expression, and purification of cold inducible RNA-binding protein and its neuroprotective mechanism of action","volume":"1597","author":"Liu","year":"2015","journal-title":"Brain Res."},{"key":"ref_21","first-page":"520","article-title":"Neuron Derived Cold-Inducible RNA-Binding Protein Promotes NETs Formation to Exacerbate Brain Endothelial Barrier Disruption after Ischemic Stroke","volume":"16","author":"Li","year":"2024","journal-title":"Aging Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.1016\/j.bbagen.2014.02.027","article-title":"Cold-inducible RNA-binding protein mediates neuroinflammation in cerebral ischemia","volume":"1840","author":"Zhou","year":"2014","journal-title":"Biochim. et Biophys. Acta"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Lapin, D., Aylar, D., Sharma, A., and Wang, P. (2025). Extracellular CIRP dysregulates microglial efferocytosis in ischemic stroke via the TLR4\/miR-155\/MafB axis. Res. Sq.","DOI":"10.21203\/rs.3.rs-7223452\/v1"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"12205","DOI":"10.1007\/s12035-025-05029-7","article-title":"Cold-Induced RNA-Binding Protein (CIRP) Affects Cerebral Ischemia-Reperfusion Injury Through NF-\u03baB Pathway","volume":"62","author":"Fan","year":"2025","journal-title":"Mol. Neurobiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"tkae004","DOI":"10.1093\/burnst\/tkae004","article-title":"Extracellular cold-inducible RNA-binding protein mediated neuroinflammation and neuronal apoptosis after traumatic brain injury","volume":"12","author":"Liu","year":"2024","journal-title":"Burn. Trauma"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e01618","DOI":"10.1002\/brb3.1618","article-title":"Cold-inducible RNA-binding protein contributes to intracerebral hemorrhage-induced brain injury via TLR4 signaling","volume":"10","author":"Zhou","year":"2020","journal-title":"Brain Behav."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5000","DOI":"10.1007\/s12035-020-02075-1","article-title":"Potential Role of Extracellular CIRP in Alcohol-Induced Alzheimer\u2019s Disease","volume":"57","author":"Sharma","year":"2020","journal-title":"Mol. Neurobiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/S0305-0491(99)00174-1","article-title":"Cloning and characterization of amphibian cold inducible RNA-binding protein","volume":"125","author":"Saito","year":"2000","journal-title":"Comp. Biochem. Physiol. Part B Biochem. Mol. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1006\/bbrc.1998.8482","article-title":"Diurnal change of the cold-inducible RNA-binding protein (Cirp) expression in mouse brain","volume":"245","author":"Nishiyama","year":"1998","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"zsx059","DOI":"10.1093\/sleep\/zsx059","article-title":"Transcriptional Profiling of Cholinergic Neurons From Basal Forebrain Identifies Changes in Expression of Genes Between Sleep and Wake","volume":"40","author":"Nikonova","year":"2017","journal-title":"Sleep"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1126\/science.1217726","article-title":"Cold-inducible RNA-binding protein modulates circadian gene expression posttranscriptionally","volume":"338","author":"Morf","year":"2012","journal-title":"Science"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1016\/j.cbpa.2008.07.027","article-title":"Cold stress and light signals induce the expression of cold-inducible RNA binding protein (cirp) in the brain and eye of the Japanese treefrog (Hyla japonica)","volume":"151","author":"Sugimoto","year":"2008","journal-title":"Comp. Biochem. Physiol. Part A Mol. Integr. Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1038\/nature06829","article-title":"Melanopsin cells are the principal conduits for rod-cone input to non-image-forming vision","volume":"453","author":"Ecker","year":"2008","journal-title":"Nature"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"Rc191","DOI":"10.1523\/JNEUROSCI.22-01-j0002.2002","article-title":"The photopigment melanopsin is exclusively present in pituitary adenylate cyclase-activating polypeptide-containing retinal ganglion cells of the retinohypothalamic tract","volume":"22","author":"Hannibal","year":"2002","journal-title":"J. Neurosci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1126\/science.1069609","article-title":"Melanopsin-containing retinal ganglion cells: Architecture, projections, and intrinsic photosensitivity","volume":"295","author":"Hattar","year":"2002","journal-title":"Science"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Riedel, C.S., Georg, B., and Hannibal, J. (2023). Phenotyping of light-activated neurons in the mouse SCN based on the expression of FOS and EGR1. Front. Physiol., 14.","DOI":"10.3389\/fphys.2023.1321007"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/S1474-4422(18)30461-7","article-title":"Association between circadian rhythms and neurodegenerative diseases","volume":"18","author":"Leng","year":"2019","journal-title":"Lancet Neurol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s41582-021-00577-7","article-title":"Circadian rhythms in neurodegenerative disorders","volume":"18","author":"Nassan","year":"2022","journal-title":"Nat. Rev. Neurol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1176\/appi.ajp.158.5.704","article-title":"Sundowning and circadian rhythms in Alzheimer\u2019s disease","volume":"158","author":"Volicer","year":"2001","journal-title":"Am. J. Psychiatry"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Canevelli, M., Valletta, M., Trebbastoni, A., Sarli, G., D\u2019Antonio, F., Tariciotti, L., de Lena, C., and Bruno, G. (2016). Sundowning in Dementia: Clinical Relevance, Pathophysiological Determinants, and Therapeutic Approaches. Front. Med., 3.","DOI":"10.3389\/fmed.2016.00073"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.5664\/jcsm.5100","article-title":"Clinical Practice Guideline for the Treatment of Intrinsic Circadian Rhythm Sleep-Wake Disorders: Advanced Sleep-Wake Phase Disorder (ASWPD), Delayed Sleep-Wake Phase Disorder (DSWPD), Non-24-Hour Sleep-Wake Rhythm Disorder (N24SWD), and Irregular Sleep-Wake Rhythm Disorder (ISWRD). An Update for 2015: An American Academy of Sleep Medicine Clinical Practice Guideline","volume":"11","author":"Auger","year":"2015","journal-title":"J. Clin. Sleep Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.jsmc.2015.08.005","article-title":"Irregular Sleep-Wake Rhythm Disorder","volume":"10","author":"Abbott","year":"2015","journal-title":"Sleep Med. Clin."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2945","DOI":"10.1016\/j.apsb.2025.04.011","article-title":"Linkage of circadian rhythm disruptions with Alzheimer\u2019s disease and therapeutic interventions","volume":"15","author":"Madamanchi","year":"2025","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1001\/jamaneurol.2013.6239","article-title":"Circadian melatonin rhythm and excessive daytime sleepiness in Parkinson disease","volume":"71","author":"Videnovic","year":"2014","journal-title":"JAMA Neurol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1212\/WNL.0000000000001737","article-title":"Development of excessive daytime sleepiness in early Parkinson disease","volume":"85","author":"Tholfsen","year":"2015","journal-title":"Neurology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1001\/jamaneurol.2014.65","article-title":"Sleep and circadian rhythm regulation in early Parkinson disease","volume":"71","author":"Breen","year":"2014","journal-title":"JAMA Neurol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Zhong, G., Bolitho, S., Grunstein, R., Naismith, S.L., and Lewis, S.J. (2013). The relationship between thermoregulation and REM sleep behaviour disorder in Parkinson\u2019s disease. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0072661"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.1007\/s00415-013-6859-5","article-title":"Nocturnal hypertension and dysautonomia in patients with Parkinson\u2019s disease: Are they related?","volume":"260","author":"Berganzo","year":"2013","journal-title":"J. Neurol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.sleep.2013.10.016","article-title":"Disturbances in melatonin secretion and circadian sleep-wake regulation in Parkinson disease","volume":"15","author":"Bolitho","year":"2014","journal-title":"Sleep Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.smrv.2016.08.001","article-title":"A systematic review of the literature on disorders of sleep and wakefulness in Parkinson\u2019s disease from 2005 to 2015","volume":"35","author":"Chahine","year":"2017","journal-title":"Sleep Med. Rev."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1001\/jamaneurol.2018.0640","article-title":"A Histologic Study of the Circadian System in Parkinson Disease, Multiple System Atrophy, and Progressive Supranuclear Palsy","volume":"75","author":"Courtney","year":"2018","journal-title":"JAMA Neurol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e12939","DOI":"10.1111\/jsr.12939","article-title":"Assessing the role of nocturnal core body temperature dysregulation as a biomarker of neurodegeneration","volume":"29","author":"Raupach","year":"2020","journal-title":"J. Sleep Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1212\/WNL.0000000000004058","article-title":"Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium","volume":"89","author":"McKeith","year":"2017","journal-title":"Neurology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1001\/archpsyc.58.4.353","article-title":"Differential circadian rhythm disturbances in men with Alzheimer disease and frontotemporal degeneration","volume":"58","author":"Harper","year":"2001","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"5389","DOI":"10.1172\/JCI70317","article-title":"Circadian clock proteins regulate neuronal redox homeostasis and neurodegeneration","volume":"123","author":"Musiek","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"110721","DOI":"10.1016\/j.pnpbp.2023.110721","article-title":"The shared molecular mechanisms underlying aging of the brain, major depressive disorder, and Alzheimer\u2019s disease: The role of circadian rhythm disturbances","volume":"123","author":"Amidfar","year":"2023","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"12115","DOI":"10.1038\/srep12115","article-title":"Fasting activates macroautophagy in neurons of Alzheimer\u2019s disease mouse model but is insufficient to degrade amyloid-beta","volume":"5","author":"Chen","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"553","DOI":"10.3109\/07420528.2015.1137581","article-title":"Circadian rhythm of autophagy proteins in hippocampus is blunted by sleep fragmentation","volume":"33","author":"He","year":"2016","journal-title":"Chronobiol. Int."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1007\/s00018-019-03314-y","article-title":"Circadian regulation of astrocyte function: Implications for Alzheimer\u2019s disease","volume":"77","author":"McKee","year":"2020","journal-title":"Cell. Mol. Life Sci. CMLS"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"115","DOI":"10.4103\/1793-5482.142690","article-title":"Better Glasgow outcome score, cerebral perfusion pressure and focal brain oxygenation in severely traumatized brain following direct regional brain hypothermia therapy: A prospective randomized study","volume":"9","author":"Idris","year":"2014","journal-title":"Asian J. Neurosurg."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1016\/j.brainres.2015.07.004","article-title":"Cold-inducible RNA-binding protein inhibits neuron apoptosis through the suppression of mitochondrial apoptosis","volume":"1622","author":"Zhang","year":"2015","journal-title":"Brain Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"114883","DOI":"10.1016\/j.expneurol.2024.114883","article-title":"Cold inducible RNA binding protein-regulated mitochondria associated endoplasmic reticulum membranes-mediated Ca(2+) transport play a critical role in hypothermia cerebral resuscitation","volume":"379","author":"Gao","year":"2024","journal-title":"Exp. Neurol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2697","DOI":"10.1007\/s12035-016-9813-6","article-title":"Therapeutic Hypothermia Enhances Cold-Inducible RNA-Binding Protein Expression and Inhibits Mitochondrial Apoptosis in a Rat Model of Cardiac Arrest","volume":"54","author":"Wu","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"ref_64","first-page":"386","article-title":"[Cold inducible RNA-binding protein inhibits hippocampal neuronal apoptosis under hypothermia by regulating redox system]","volume":"67","author":"Li","year":"2015","journal-title":"Sheng Li Xue Bao [Acta Physiol. Sin.]"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.brainres.2011.12.053","article-title":"Cold-inducible RNA binding protein inhibits H2O2-induced apoptosis in rat cortical neurons","volume":"1441","author":"Li","year":"2012","journal-title":"Brain Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1093\/nar\/gkj519","article-title":"Post-transcriptional regulation of thioredoxin by the stress inducible heterogenous ribonucleoprotein A18","volume":"34","author":"Yang","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"148429","DOI":"10.1016\/j.ijbiomac.2025.148429","article-title":"The pathological roles of thioredoxin-interacting protein in ischemic stroke, focusing on oxidative stress and pyroptosis","volume":"331","author":"Lu","year":"2025","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Salameh, A., Dhein, S., D\u00e4hnert, I., and Klein, N. (2016). Neuroprotective Strategies during Cardiac Surgery with Cardiopulmonary Bypass. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17111945"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1093\/ejcts\/ezaa216","article-title":"Blood pressure and brain injury in cardiac surgery: A secondary analysis of a randomized trial","volume":"58","author":"Vedel","year":"2020","journal-title":"Eur. J. Cardio-Thorac. Surg."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e25446","DOI":"10.1097\/MD.0000000000025446","article-title":"Plasma S100\u03b2 and neuron-specific enolase, but not neuroglobin, are associated with early cognitive dysfunction after total arch replacement surgery: A pilot study","volume":"100","author":"Wan","year":"2021","journal-title":"Medicine"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.brainres.2010.05.029","article-title":"Effects of hypothermia and cerebral ischemia on cold-inducible RNA-binding protein mRNA expression in rat brain","volume":"1347","author":"Liu","year":"2010","journal-title":"Brain Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s12035-012-8344-z","article-title":"Molecular mechanisms of ischemia-reperfusion injury in brain: Pivotal role of the mitochondrial membrane potential in reactive oxygen species generation","volume":"47","author":"Sanderson","year":"2013","journal-title":"Mol. Neurobiol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/s41580-020-0230-3","article-title":"Reactive oxygen species (ROS) as pleiotropic physiological signalling agents","volume":"21","author":"Sies","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.ejphar.2010.09.033","article-title":"The cytotoxic mechanism of malondialdehyde and protective effect of carnosine via protein cross-linking\/mitochondrial dysfunction\/reactive oxygen species\/MAPK pathway in neurons","volume":"650","author":"Cheng","year":"2011","journal-title":"Eur. J. Pharmacol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1007\/s10565-008-9097-3","article-title":"Carbonyl stress: Malondialdehyde induces damage on rat hippocampal neurons by disturbance of Ca(2+) homeostasis","volume":"25","author":"Cai","year":"2009","journal-title":"Cell Biol. Toxicol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2648","DOI":"10.4014\/jmb.2409.09003","article-title":"Ischemic Stroke Induces ROS Accumulation, Maladaptive Mitophagy, and Neuronal Apoptosis in Minipigs","volume":"34","author":"Chen","year":"2024","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1016\/S0891-5849(99)00158-6","article-title":"Effects of ischemia and H2O2 on the cold stress protein CIRP expression in rat neuronal cells","volume":"27","author":"Xue","year":"1999","journal-title":"Free Radic. Biol. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1016\/j.surg.2018.06.048","article-title":"Cold-inducible RNA-binding protein-derived peptide C23 attenuates inflammation and tissue injury in a murine model of intestinal ischemia-reperfusion","volume":"164","author":"McGinn","year":"2018","journal-title":"Surgery"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.surg.2016.04.014","article-title":"Deficiency of cold-inducible ribonucleic acid-binding protein reduces renal injury after ischemia-reperfusion","volume":"160","author":"Cen","year":"2016","journal-title":"Surgery"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Dai, H., Zhou, Y., Lu, Y., Zhang, X., Zhuang, Z., Gao, Y., Liu, G., Chen, C., Ma, J., and Li, W. (2022). Decreased Expression of CIRP Induced by Therapeutic Hypothermia Correlates with Reduced Early Brain Injury after Subarachnoid Hemorrhage. J. Clin. Med., 11.","DOI":"10.3390\/jcm11123411"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2609","DOI":"10.1172\/JCI78443","article-title":"Microglia regulate blood clearance in subarachnoid hemorrhage by heme oxygenase-1","volume":"125","author":"Schallner","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1161\/STROKEAHA.115.011956","article-title":"Heme-Hemopexin Scavenging Is Active in the Brain and Associates With Outcome After Subarachnoid Hemorrhage","volume":"47","author":"Garland","year":"2016","journal-title":"Stroke"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"832","DOI":"10.2174\/1567201813666161025115531","article-title":"The Updated Role of Oxidative Stress in Subarachnoid Hemorrhage","volume":"14","author":"Yang","year":"2017","journal-title":"Curr. Drug Deliv."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.2174\/1570159X19666211101103646","article-title":"New Mechanisms and Targets of Subarachnoid Hemorrhage: A Focus on Mitochondria","volume":"20","author":"Zhang","year":"2022","journal-title":"Curr. Neuropharmacol."},{"key":"ref_85","first-page":"H869","article-title":"Hypothermia reduces cerebral metabolic rate and cerebral blood flow in newborn pigs","volume":"253","author":"Busija","year":"1987","journal-title":"Am. J. Physiol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1097\/00008506-199507000-00021","article-title":"Cerebral metabolic rate and hypothermia: Their relationship with ischemic neurologic injury","volume":"7","author":"Lanier","year":"1995","journal-title":"J. Neurosurg. Anesthesiol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1007\/s10495-022-01799-w","article-title":"Mild hypothermia alleviates oxygen-glucose deprivation\/reperfusion-induced apoptosis by inhibiting ROS generation, improving mitochondrial dysfunction and regulating DNA damage repair pathway in PC12 cells","volume":"28","author":"Zhou","year":"2023","journal-title":"Apoptosis Int. J. Program. Cell Death"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"7687","DOI":"10.2147\/JIR.S491885","article-title":"Moderate Hypothermia Alleviates Sepsis-Associated Acute Lung Injury by Suppressing Ferroptosis Induced by Excessive Inflammation and Oxidative Stress via the Keap1\/GSK3\u03b2\/Nrf2\/GPX4 Signaling Pathway","volume":"17","author":"Xu","year":"2024","journal-title":"J. Inflamm. Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2431","DOI":"10.1016\/j.jtcvs.2019.06.115","article-title":"A novel target to reduce microglial inflammation and neuronal damage after deep hypothermic circulatory arrest","volume":"159","author":"Liu","year":"2020","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Li, M., Yao, M., Shao, K., Shen, X., Ge, Z., and Li, Y. (2023). Serum cold-inducible RNA-binding protein (CIRP) levels as a prognostic indicator in patients with acute ischemic stroke. Front. Neurol., 14.","DOI":"10.3389\/fneur.2023.1211108"},{"key":"ref_91","first-page":"143","article-title":"Cold Inducible RNA-Binding Protein Promotes the Development of Alzheimer\u2019s Disease Partly by Inhibition of uPA in Astrocytes","volume":"14","author":"Li","year":"2024","journal-title":"Degener. Neurol. Neuromuscul. Dis."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1056\/NEJMra2201449","article-title":"Spontaneous Intracerebral Hemorrhage","volume":"387","author":"Sheth","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1016\/S1474-4422(22)00309-X","article-title":"Traumatic brain injury: Progress and challenges in prevention, clinical care, and research","volume":"21","author":"Maas","year":"2022","journal-title":"Lancet Neurol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1016\/S0140-6736(20)32205-4","article-title":"Alzheimer\u2019s disease","volume":"397","author":"Scheltens","year":"2021","journal-title":"Lancet"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s10020-019-0092-3","article-title":"Extracellular cold inducible RNA-binding protein mediates binge alcohol-induced brain hypoactivity and impaired cognition in mice","volume":"25","author":"Jacob","year":"2019","journal-title":"Mol. Med."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13195-018-0453-0","article-title":"Alcohol use and dementia: A systematic scoping review","volume":"11","author":"Rehm","year":"2019","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/alzrt157","article-title":"Alcohol-related dementia: An update of the evidence","volume":"5","author":"Ridley","year":"2013","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1016\/j.jpedsurg.2018.12.020","article-title":"C23, an oligopeptide derived from cold-inducible RNA-binding protein, suppresses inflammation and reduces lung injury in neonatal sepsis","volume":"54","author":"Denning","year":"2019","journal-title":"J. Pediatr. Surg."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/s12979-023-00383-3","article-title":"Toll-like receptor 4 (TLR4): New insight immune and aging","volume":"20","author":"Kim","year":"2023","journal-title":"Immun. Ageing"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s12964-023-01387-8","article-title":"Free heme induces neuroinflammation and cognitive impairment by microglial activation via the TLR4\/MyD88\/NF-\u03baB signaling pathway","volume":"22","author":"Wei","year":"2024","journal-title":"Cell Commun. Signal. CCS"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Ali, W., Choe, K., Park, J.S., Ahmad, R., Park, H.Y., Kang, M.H., Park, T.J., and Kim, M.O. (2024). Kojic acid reverses LPS-induced neuroinflammation and cognitive impairment by regulating the TLR4\/NF-\u03baB signaling pathway. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1443552"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2449","DOI":"10.1080\/21655979.2021.1935066","article-title":"MicroRNA-155 influences cell damage in ischemic stroke via TLR4\/MYD88 signaling pathway","volume":"12","author":"Chen","year":"2021","journal-title":"Bioengineered"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1126\/science.1087262","article-title":"Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway","volume":"301","author":"Yamamoto","year":"2003","journal-title":"Science"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Ye, L., Tang, X., Liu, F., Wei, T., Xu, T., Jiang, Z., Xu, L., Xiang, C., Yuan, X., and Shen, L. (2025). Targeting CIRP and IL-6R-mediated microglial inflammation to improve outcomes in intracerebral hemorrhage. J. Adv. Res.","DOI":"10.1016\/j.jare.2025.09.012"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"3311","DOI":"10.1007\/s12035-023-03273-3","article-title":"Extracellular CIRP Induces Calpain Activation in Neurons via PLC-IP(3)-Dependent Calcium Pathway","volume":"60","author":"Sharma","year":"2023","journal-title":"Mol. Neurobiol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.bj.2018.01.003","article-title":"Tau and neuroinflammation: What impact for Alzheimer\u2019s Disease and Tauopathies?","volume":"41","author":"Laurent","year":"2018","journal-title":"Biomed. J."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"3240","DOI":"10.1172\/JCI90606","article-title":"Microglia in Alzheimer\u2019s disease","volume":"127","author":"Sarlus","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/1742-2094-9-46","article-title":"Heme activates TLR4-mediated inflammatory injury via MyD88\/TRIF signaling pathway in intracerebral hemorrhage","volume":"9","author":"Lin","year":"2012","journal-title":"J. Neuroinflamm."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/s41572-019-0118-8","article-title":"Ischaemic stroke","volume":"5","author":"Campbell","year":"2019","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"C343","DOI":"10.1152\/ajpcell.00095.2018","article-title":"Blood-brain barrier dysfunction in ischemic stroke: Targeting tight junctions and transporters for vascular protection","volume":"315","author":"Abdullahi","year":"2018","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Ma, Y., Yang, X., Chatterjee, V., Meegan, J.E., Beard, R.S., and Yuan, S.Y. (2019). Role of Neutrophil Extracellular Traps and Vesicles in Regulating Vascular Endothelial Permeability. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.01037"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"7583","DOI":"10.1007\/s12035-024-04060-4","article-title":"Mechanism of Efferocytosis in Determining Ischaemic Stroke Resolution-Diving into Microglia\/Macrophage Functions and Therapeutic Modality","volume":"61","author":"Xie","year":"2024","journal-title":"Mol. Neurobiol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1002\/glia.22836","article-title":"Astrocyte development: A Guide for the Perplexed","volume":"63","author":"Molofsky","year":"2015","journal-title":"Glia"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1002\/glia.24146","article-title":"Astrocytic p75(NTR) expression provoked by ischemic stroke exacerbates the blood-brain barrier disruption","volume":"70","author":"Qin","year":"2022","journal-title":"Glia"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/nature21029","article-title":"Neurotoxic reactive astrocytes are induced by activated microglia","volume":"541","author":"Liddelow","year":"2017","journal-title":"Nature"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1126\/science.aad8373","article-title":"Complement and microglia mediate early synapse loss in Alzheimer mouse models","volume":"352","author":"Hong","year":"2016","journal-title":"Science"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"e14636","DOI":"10.1111\/cns.14636","article-title":"Fat mass and obesity associated protein inhibits neuronal ferroptosis via the FYN\/Drp1 axis and alleviate cerebral ischemia\/reperfusion injury","volume":"30","author":"Zhang","year":"2024","journal-title":"CNS Neurosci. Ther."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/j.jconrel.2024.02.039","article-title":"Stepwise targeted strategies for improving neurological function by inhibiting oxidative stress levels and inflammation following ischemic stroke","volume":"368","author":"Li","year":"2024","journal-title":"J. Control. Release"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.21037\/atm-21-5752","article-title":"Salidroside inhibits NLRP3 inflammasome activation and apoptosis in microglia induced by cerebral ischemia\/reperfusion injury by inhibiting the TLR4\/NF-\u03baB signaling pathway","volume":"9","author":"Liu","year":"2021","journal-title":"Ann. Transl. Med."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.neuroscience.2024.12.020","article-title":"HO-1 represses NF-\u03baB signaling pathway to mediate microglia polarization and phagocytosis in intracerebral hemorrhage","volume":"566","author":"Chen","year":"2025","journal-title":"Neuroscience"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.alcohol.2019.11.002","article-title":"Interaction effect of alcohol consumption and Alzheimer disease polygenic risk score on the brain cortical thickness of cognitively normal subjects","volume":"85","author":"Matloff","year":"2020","journal-title":"Alcohol"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.2174\/1567205013666160603005035","article-title":"The Association Between Alcohol Use and the Progression of Alzheimer\u2019s Disease","volume":"13","author":"Heymann","year":"2016","journal-title":"Curr. Alzheimer Res."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.jalz.2019.09.086","article-title":"Association between alcohol consumption and Alzheimer\u2019s disease: A Mendelian randomization study","volume":"16","author":"Andrews","year":"2020","journal-title":"Alzheimer\u2019s Dement. J. Alzheimer\u2019s Assoc."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"e124","DOI":"10.1016\/S2468-2667(18)30022-7","article-title":"Contribution of alcohol use disorders to the burden of dementia in France 2008-13: A nationwide retrospective cohort study","volume":"3","author":"Schwarzinger","year":"2018","journal-title":"Lancet Public Health"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"3628","DOI":"10.1007\/s12035-021-02368-z","article-title":"Extracellular CIRP Activates the IL-6R\u03b1\/STAT3\/Cdk5 Pathway in Neurons","volume":"58","author":"Sharma","year":"2021","journal-title":"Mol. Neurobiol."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Rajayer, S.R., Jacob, A., Yang, W.L., Zhou, M., Chaung, W., and Wang, P. (2013). Cold-inducible RNA-binding protein is an important mediator of alcohol-induced brain inflammation. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0079430"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.alcohol.2009.10.003","article-title":"Mechanisms involved in the neurotoxic, cognitive, and neurobehavioral effects of alcohol consumption during adolescence","volume":"44","author":"Guerri","year":"2010","journal-title":"Alcohol"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1146\/annurev-clinpsy-050212-185610","article-title":"Neurotoxic effects of alcohol in adolescence","volume":"9","author":"Jacobus","year":"2013","journal-title":"Annu. Rev. Clin. Psychol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1186\/s12974-021-02246-4","article-title":"MD2 contributes to the pathogenesis of perioperative neurocognitive disorder via the regulation of \u03b15GABA(A) receptors in aged mice","volume":"18","author":"Zuo","year":"2021","journal-title":"J. Neuroinflamm."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"114291","DOI":"10.1016\/j.ejmech.2022.114291","article-title":"Toll-like receptor 4 (TLR4) inhibitors: Current research and prospective","volume":"235","author":"Zhang","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"5814","DOI":"10.1007\/s12035-021-02519-2","article-title":"Generation and Role of Calpain-Cleaved 17-kDa Tau Fragment in Acute Ischemic Stroke","volume":"58","author":"Chen","year":"2021","journal-title":"Mol. Neurobiol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"8104","DOI":"10.1007\/s12035-024-04092-w","article-title":"Involvement of Calpain in Neurovascular Unit Damage through Up-regulating PARP-NF-\u03baB Signaling during Experimental Ischemic Stroke","volume":"61","author":"Yan","year":"2024","journal-title":"Mol. Neurobiol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s12974-025-03373-y","article-title":"Cinnamaldehyde and its combination with deferoxamine ameliorate inflammation, ferroptosis and hematoma expansion after intracerebral hemorrhage in mice","volume":"22","author":"Liu","year":"2025","journal-title":"J. Neuroinflamm."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nm.3806","article-title":"A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases","volume":"21","author":"Coll","year":"2015","journal-title":"Nat. Med."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"4758","DOI":"10.1016\/j.jprot.2012.01.033","article-title":"Differentiating ischemic from hemorrhagic stroke using plasma biomarkers: The S100B\/RAGE pathway","volume":"75","author":"Montaner","year":"2012","journal-title":"J. Proteom."},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Drago\u0219, H.M., Stan, A., Pintican, R., Feier, D., Lebovici, A., Panaitescu, P., Dina, C., Strilciuc, S., and Muresanu, D.F. (2023). MRI Radiomics and Predictive Models in Assessing Ischemic Stroke Outcome-A Systematic Review. Diagnostics, 13.","DOI":"10.3390\/diagnostics13050857"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"6330","DOI":"10.1007\/s00415-022-11284-8","article-title":"Elevated inflammatory biomarkers and poor outcomes in intracerebral hemorrhage","volume":"269","author":"Bader","year":"2022","journal-title":"J. Neurol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1111\/j.1365-2796.2005.01514.x","article-title":"Prognostic role of C-reactive protein in very old patients with acute ischaemic stroke","volume":"258","author":"Masotti","year":"2005","journal-title":"J. Intern. Med."},{"key":"ref_139","first-page":"Cd004128","article-title":"Hypothermia for neuroprotection in adults after cardiac arrest","volume":"5","author":"Arrich","year":"2023","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1111\/dmcn.14610","article-title":"Combination treatments with therapeutic hypothermia for hypoxic-ischemic neuroprotection","volume":"62","author":"Zhou","year":"2020","journal-title":"Dev. Med. Child Neurol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.peptides.2015.03.010","article-title":"Peptides and the blood-brain barrier","volume":"72","author":"Banks","year":"2015","journal-title":"Peptides"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1038\/s42003-025-07772-y","article-title":"CIRP contributes to multiple organ damage in acute pancreatitis by increasing endothelial permeability","volume":"8","author":"Liu","year":"2025","journal-title":"Commun. Biol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1038\/s41420-024-01923-6","article-title":"Blocking CIRP protects against acute pancreatitis by improving mitochondrial function and suppressing pyroptosis in acinar cells","volume":"10","author":"Liu","year":"2024","journal-title":"Cell Death Discov."},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Xu, Q., Wang, M., Guo, H., Liu, H., Zhang, G., Xu, C., and Chen, H. (2021). Emodin Alleviates Severe Acute Pancreatitis-Associated Acute Lung Injury by Inhibiting the Cold-Inducible RNA-Binding Protein (CIRP)-Mediated Activation of the NLRP3\/IL-1\u03b2\/CXCL1 Signaling. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.655372"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"111924","DOI":"10.1016\/j.intimp.2024.111924","article-title":"CIRP increases Foxp3(+) regulatory T cells and inhibits development of Th17 cells by enhancing TLR4-IL-2 signaling in the late phase of sepsis","volume":"132","author":"Wu","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"ref_146","doi-asserted-by":"crossref","unstructured":"Shimizu, J., Murao, A., Nofi, C., Wang, P., and Aziz, M. (2022). Extracellular CIRP Promotes GPX4-Mediated Ferroptosis in Sepsis. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.903859"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"3052","DOI":"10.1038\/s41598-017-13139-z","article-title":"A cold-inducible RNA-binding protein (CIRP)-derived peptide attenuates inflammation and organ injury in septic mice","volume":"8","author":"Zhang","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1042\/BSR20241398","article-title":"Hydrogen sulfide attenuates sepsis-induced cardiac dysfunction in infant rats by inhibiting the expression of cold-inducible RNA-binding protein","volume":"45","author":"Li","year":"2025","journal-title":"Biosci. Rep."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.4254\/wjh.v16.i9.1278","article-title":"C23 ameliorates carbon tetrachloride-induced liver fibrosis in mice","volume":"16","author":"Tang","year":"2024","journal-title":"World J. Hepatol."},{"key":"ref_150","doi-asserted-by":"crossref","unstructured":"Bolourani, S., Sari, E., Brenner, M., and Wang, P. (2022). The role of eCIRP in bleomycin-induced pulmonary fibrosis in mice. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0266163"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1097\/SHK.0000000000002113","article-title":"The Protective Effect of C23 in A Rat Model of Cardiac Arrest And Resuscitation","volume":"59","author":"Gao","year":"2023","journal-title":"Shock"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"11310","DOI":"10.1111\/jcmm.17062","article-title":"Normothermic machine perfusion attenuates hepatic ischaemia-reperfusion injury by inhibiting CIRP-mediated oxidative stress and mitochondrial fission","volume":"25","author":"Liu","year":"2021","journal-title":"J. Cell. Mol. Med."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s10020-025-01071-2","article-title":"An eCIRP inhibitor attenuates fibrosis and ferroptosis in ischemia and reperfusion induced chronic kidney disease","volume":"31","author":"Zhang","year":"2025","journal-title":"Mol. Med."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1097\/SHK.0000000000000988","article-title":"The Protective Effect of A Short Peptide Derived From Cold-Inducible RNA-Binding Protein in Renal Ischemia-Reperfusion Injury","volume":"49","author":"McGinn","year":"2018","journal-title":"Shock"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"3576892","DOI":"10.1155\/2022\/3576892","article-title":"Change in Oxidative Stress and Mitochondrial Dynamics in Response to Elevated Cold-Inducible RNA-Binding Protein in Cardiac Surgery-Associated Acute Kidney Injury","volume":"2022","author":"Zheng","year":"2022","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"5978271","DOI":"10.1155\/2022\/5978271","article-title":"Extracellular CIRP Upregulates Proinflammatory Cytokine Expression via the NF-kappaB and ERK1\/2 Signaling Pathways in Psoriatic Keratinocytes","volume":"2022","author":"Zhang","year":"2022","journal-title":"Mediat. Inflamm."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"42","DOI":"10.3892\/ijmm.2025.5483","article-title":"Intracellular CIRP promotes liver regeneration via STAT3 signaling pathway activation after partial hepatectomy in mice","volume":"55","author":"Wang","year":"2025","journal-title":"Int. J. Mol. Med."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"e250562","DOI":"10.1001\/jamanetworkopen.2025.0562","article-title":"Sex Differences in Apolipoprotein E and Alzheimer Disease Pathology Across Ancestries","volume":"8","author":"Xu","year":"2025","journal-title":"JAMA Netw. Open"},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Huang, X., Li, S., Qiu, N., Ni, A., Xiong, T., Xue, J., and Yin, K.J. (2024). Sex and Age-Dependent Effects of miR-15a\/16-1 Antagomir on Ischemic Stroke Outcomes. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252111765"}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/16\/2\/205\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T16:31:15Z","timestamp":1770654675000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/16\/2\/205"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,9]]},"references-count":159,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["brainsci16020205"],"URL":"https:\/\/doi.org\/10.3390\/brainsci16020205","relation":{},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,9]]}}}