{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:41Z","timestamp":1787028581707,"version":"build-2736575974"},"reference-count":125,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017638","name":"Ministry of Health of the Russian Federation","doi-asserted-by":"crossref","award":["200103056"],"award-info":[{"award-number":["200103056"]}],"id":[{"id":"10.13039\/501100017638","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The heart\u2013brain axis is a bidirectional communication network composed of neural, humoral, and immune pathways that sustain cardiovascular and brain homeostasis. There is mounting evidence that viral myocarditis\u2014a prototype of inflammatory heart disease\u2014acts beyond the myocardium, triggering systemic immune cascades that lead to central nervous system (CNS) involvement. This involvement creates an inflammatory continuum in which cardiac damage and neuroinflammation reinforce each other via common cytokine and molecular mediators. Central mediators in this axis are the proinflammatory cytokines IL-1\u03b2, IL-6, tumor necrosis factor (TNF)-\u03b1, IL-17, IL-23, and IL-33. These cytokines are released by infected cardiomyocytes and immune cells during myocarditis, inducing endothelial cell (EC) activation, and causing blood\u2013brain barrier (BBB) disruption. Simultaneously, TLR\/NF-\u03baB signaling and the stability of endothelial junctions are modulated by regulatory microRNAs such as miR-155 and miR-146a\/b, which respectively enhance or attenuate inflammatory signals. Disruption of the BBB allows cytokines and immune cells to enter the brain parenchyma, where they activate microglia and astrocytes through NF-\u03baB-dependent pathways. The resultant neuroinflammation disrupts autonomic equilibrium and leads to sympathetic overdrive, arrhythmogenesis, and overall worsening of cardiac injury, thus forming a self-perpetuating inflammatory cycle between the heart and the brain. Selective modulation of cytokines (anti-IL-1\u03b2, IL-6 receptor antagonists, and TNF-\u03b1 modulators), blockade of the NLRP3 inflammasome, and miRNA therapy (anti-miR-155 and miR-146a mimics) are potential approaches for interrupting the heart\u2013brain inflammatory circuit. In addition, neurotrophic therapies preserving BBB integrity may reduce secondary neuronal damage. Therefore, a future precision cardio-neuroprotective paradigm will rely on the integration of anti-inflammatory, molecular, and neurovascular strategies aimed at limiting systemic cytokine propagation and restoring bidirectional homeostasis through the heart\u2013brain axis.<\/jats:p>","DOI":"10.3390\/ijms27062603","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T13:12:24Z","timestamp":1773321144000},"page":"2603","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Heart\u2013Brain Axis in Viral Myocarditis: Shared Cytokine Pathways, Blood\u2013Brain Barrier Crosstalk, and Neuroinflammatory Consequences"],"prefix":"10.3390","volume":"27","author":[{"given":"Vadim M.","family":"Mitrokhin","sequence":"first","affiliation":[{"name":"Department of Fundamental and Applied Physiology, Russian States Medical University, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre G.","family":"Kamkin","sequence":"additional","affiliation":[{"name":"Department of Fundamental and Applied Physiology, Russian States Medical University, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina I.","family":"Babkina","sequence":"additional","affiliation":[{"name":"Department of Fundamental and Applied Physiology, Russian States Medical University, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina G.","family":"Savinkova","sequence":"additional","affiliation":[{"name":"Department of Fundamental and Applied Physiology, Russian States Medical University, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1508-272X","authenticated-orcid":false,"given":"Stanislav A.","family":"Shileiko","sequence":"additional","affiliation":[{"name":"Department of Fundamental and Applied Physiology, Russian States Medical University, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman S.","family":"Ovchinnikov","sequence":"additional","affiliation":[{"name":"Department of Fundamental and Applied Physiology, Russian States Medical University, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3475-2131","authenticated-orcid":false,"given":"Mitko I.","family":"Mladenov","sequence":"additional","affiliation":[{"name":"Department of Fundamental and Applied Physiology, Russian States Medical University, 117997 Moscow, Russia"},{"name":"Institute of Biology, Faculty of Natural Sciences and Mathematics, Ss. Cyril and Methodius University, 1000 Skopje, North Macedonia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1161\/CIRCRESAHA.117.311170","article-title":"Brain\u2013Heart Interaction: Cardiac Complications After Stroke","volume":"121","author":"Chen","year":"2017","journal-title":"Circ. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1007\/s11886-023-01990-8","article-title":"The Brain\u2013Heart Axis: Neuroinflammatory Interactions in Cardiovascular Disease","volume":"25","author":"Hu","year":"2023","journal-title":"Curr. Cardiol. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1161\/STROKEAHA.121.037316","article-title":"Stroke\u2013Heart Syndrome: Incidence and Clinical Outcomes of Cardiac Complications Following Stroke","volume":"53","author":"Buckley","year":"2022","journal-title":"Stroke"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Yang, J., Ran, M., Li, H., Lin, Y., Ma, K., Yang, Y., Fu, X., and Yang, S. (2022). New Insight into Neurological Degeneration: Inflammatory Cytokines and Blood\u2013Brain Barrier. Front. Mol. Neurosci., 15.","DOI":"10.3389\/fnmol.2022.1013933"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Gryka-Marton, M., Grabowska, A.D., and Szukiewicz, D. (2025). Breaking the Barrier: The Role of Proinflammatory Cytokines in BBB Dysfunction. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26083532"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Lin, C.-H., Yen, C.-C., Hsu, Y.-T., Chen, H.-H., Cheng, P.-W., Tseng, C.-J., Lo, Y.-K., and Chan, J.Y.H. (2019). Baroreceptor Sensitivity Predicts Functional Outcome and Complications after Acute Ischemic Stroke. J. Clin. Med., 8.","DOI":"10.3390\/jcm8030300"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.ijcard.2019.04.003","article-title":"Neuroinflammation as a Mechanism for Cardiovascular Diseases","volume":"288","author":"Rajendran","year":"2019","journal-title":"Int. J. Cardiol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Zheng, S.-Y., and Dong, J.-Z. (2022). Role of Toll-Like Receptors and Th Responses in Viral Myocarditis. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.843891"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Vicenzetto, C., Giordani, A.S., Menghi, C., Baritussio, A., Peloso Cattini, M.G., Pontara, E., Bison, E., Rizzo, S., De Gaspari, M., and Basso, C. (2024). The Role of the Immune System in Pathobiology and Therapy of Myocarditis: A Review. Biomedicines, 12.","DOI":"10.3390\/biomedicines12061156"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Xu, J., Chen, X., Guan, X., Zhang, H., Liu, Y., and Zhang, M. (2025). Therapeutic Frontiers in Viral Myocarditis: Targeting Inflammation, Viruses, Oxidative Stress, and Myocardial Repair. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1643502"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Sozzi, F.B., Gherbesi, E., Faggiano, A., Gnan, E., Maruccio, A., Schiavone, M., Iacuzio, L., and Carugo, S. (2022). Viral Myocarditis: Classification, Diagnosis, and Clinical Implications. Front. Cardiovasc. Med., 9.","DOI":"10.3389\/fcvm.2022.908663"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1161\/CIRCULATIONAHA.122.060860","article-title":"NLRP3 Inflammasome Activation Through Heart\u2013Brain Interaction Initiates Cardiac Inflammation and Hypertrophy During Pressure Overload","volume":"147","author":"Higashikuni","year":"2023","journal-title":"Circulation"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1038\/s41423-025-01284-9","article-title":"Updated Insights into the Molecular Networks for NLRP3 Inflammasome Activation","volume":"22","author":"Paik","year":"2025","journal-title":"Cell. Mol. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1038\/s41569-020-00435-x","article-title":"Myocarditis and Inflammatory Cardiomyopathy: Current Evidence and Future Directions","volume":"18","author":"Ammirati","year":"2021","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2636","DOI":"10.1093\/eurheartj\/eht210","article-title":"Current State of Knowledge on Aetiology, Diagnosis, Management, and Therapy of Myocarditis: A Position Statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases","volume":"34","author":"Caforio","year":"2013","journal-title":"Eur. Heart J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1146\/annurev.pathmechdis.3.121806.151534","article-title":"Molecular Biology and Pathogenesis of Viral Myocarditis","volume":"3","author":"Esfandiarei","year":"2008","journal-title":"Annu. Rev. Pathol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1042\/CS20020263","article-title":"Expression of Toll-Like Receptor 4 Is Associated with Enteroviral Replication in Human Myocarditis","volume":"104","author":"Satoh","year":"2003","journal-title":"Clin. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1161\/CIRCRESAHA.120.315937","article-title":"Interleukin-1 and the Inflammasome as Therapeutic Targets in Cardiovascular Disease","volume":"126","author":"Abbate","year":"2020","journal-title":"Circ. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.cpcardiol.2012.07.003","article-title":"Sex and Gender Differences in Myocarditis and Dilated Cardiomyopathy","volume":"38","author":"Fairweather","year":"2013","journal-title":"Curr. Probl. Cardiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1056\/NEJMc0911362","article-title":"Human Parvovirus B19-Associated Myocarditis","volume":"362","author":"Bock","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1093\/cvr\/cvt091","article-title":"The NLRP3 Inflammasome Is Up-Regulated in Cardiac Fibroblasts and Mediates Myocardial Ischaemia\u2013Reperfusion Injury","volume":"99","author":"Sandanger","year":"2013","journal-title":"Cardiovasc. Res."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Soulaidopoulos, S., Tousoulis, D., Sagris, M., Aghayan, S., Platanias, K., Giannakodimos, A., Lazarou, E., Tsioufis, K., and Lazaros, G. (2025). Inflammatory Mechanisms in Myocarditis\u2014Recent Therapeutic Strategies. Biomolecules, 15.","DOI":"10.3390\/biom15101475"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1056\/NEJMra0800028","article-title":"Myocarditis","volume":"360","author":"Cooper","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1038\/nrcardio.2015.108","article-title":"Viral Myocarditis\u2014Diagnosis, Treatment Options, and Current Controversies","volume":"12","author":"Pollack","year":"2015","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1007\/s11910-022-01203-9","article-title":"Neurological Manifestations of Myocarditis","volume":"22","author":"Trifan","year":"2022","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref_26","first-page":"16","article-title":"The Neurocardiogenic Spectrum in Subarachnoid Hemorrhage: A Case Report and Review of the Literature","volume":"1","author":"Mansella","year":"2017","journal-title":"Clin. Pract. Cases Emerg. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4813","DOI":"10.1007\/s00415-024-12480-4","article-title":"Stroke\u2013Heart Syndrome: Current Progress and Future Outlook","volume":"271","author":"Wang","year":"2024","journal-title":"J. Neurol."},{"key":"ref_28","first-page":"7845","article-title":"Left Ventricular Systolic Dysfunction Predicts Clinical Prognosis in Patients with Acute Ischemic Stroke after Intravenous Thrombolysis","volume":"16","author":"Zhang","year":"2024","journal-title":"Aging"},{"key":"ref_29","first-page":"e74899","article-title":"A Narrative Review of the Role of Blood Biomarkers in the Risk Prediction of Cardiovascular Diseases","volume":"16","author":"Garady","year":"2024","journal-title":"Cureus"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1546","DOI":"10.1161\/CIRCRESAHA.123.322791","article-title":"Cardiovascular Brain Circuits","volume":"132","author":"Mohanta","year":"2023","journal-title":"Circ. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1016\/S1474-4422(18)30336-3","article-title":"Stroke\u2013Heart Syndrome: Clinical Presentation and Underlying Mechanisms","volume":"17","author":"Scheitz","year":"2018","journal-title":"Lancet Neurol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e2307698","DOI":"10.1002\/advs.202307698","article-title":"Stroke-Related Brain\u2013Heart Crosstalk: Pathophysiology, Clinical Implications, and Underlying Mechanisms","volume":"11","author":"Fan","year":"2024","journal-title":"Adv. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"R429","DOI":"10.1152\/ajpregu.00051.2015","article-title":"Central Mechanisms Regulating Coordinated Cardiovascular and Respiratory Function during Stress and Arousal","volume":"309","author":"Dampney","year":"2015","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Bonaz, B., Sinniger, V., and Pellissier, S. (2017). The Vagus Nerve in the Neuro\u2013Immune Axis: Implications in the Pathology of the Gastrointestinal Tract. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.01452"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Zhao, S., Dai, Y., Ning, X., Tang, M., Zhao, Y., Li, Z., and Zhang, S. (2021). Vagus Nerve Stimulation in Early Stage of Acute Myocardial Infarction Prevents Ventricular Arrhythmias and Cardiac Remodeling. Front. Cardiovasc. Med., 8.","DOI":"10.3389\/fcvm.2021.648910"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1161\/01.HYP.0000246614.47231.25","article-title":"Novel Mechanisms of Sympathetic Regulation in Chronic Heart Failure","volume":"48","author":"Zucker","year":"2006","journal-title":"Hypertension"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1007\/s11906-024-01301-8","article-title":"Neuroimmunology of Cardiovascular Disease","volume":"26","author":"Zarate","year":"2024","journal-title":"Curr. Hypertens. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1002\/j.2040-4603.2015.tb00614.x","article-title":"Autonomic Adjustments to Exercise in Humans","volume":"5","author":"Fisher","year":"2015","journal-title":"Compr. Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2489","DOI":"10.1038\/s41423-021-00757-x","article-title":"The Blood\u2013Brain Barrier in Systemic Infection and Inflammation","volume":"18","author":"Galea","year":"2021","journal-title":"Cell. Mol. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3083","DOI":"10.2147\/JIR.S350109","article-title":"Microglia-Mediated Neuroinflammation: A Potential Target for the Treatment of Cardiovascular Diseases","volume":"15","author":"Wang","year":"2022","journal-title":"J. Inflamm. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/s10571-015-0308-1","article-title":"Microvascular Dysfunction and Cognitive Impairment","volume":"36","author":"Faraci","year":"2016","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Chong, S.Y., Lee, C.K., Huang, C., Ou, Y.H., Charles, C.J., Richards, A.M., Neupane, Y.R., Vazquez Pavon, M., Zharkova, O., and Pastorin, G. (2019). Extracellular Vesicles in Cardiovascular Diseases: Alternative Biomarker Sources, Therapeutic Agents, and Drug Delivery Carriers. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20133272"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1038\/nrcardio.2017.7","article-title":"Extracellular vesicles in coronary artery disease","volume":"14","author":"Boulanger","year":"2017","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Marostica, G., Gelibter, S., Gironi, M., Nigro, A., and Furlan, R. (2021). Extracellular Vesicles in Neuroinflammation. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.623039"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1093\/biosci\/biv084","article-title":"Extracellular Vesicles: Composition, Biological Relevance, and Methods of Study","volume":"65","author":"Zaborowski","year":"2015","journal-title":"Bioscience"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"R1335","DOI":"10.1152\/ajpregu.00255.2004","article-title":"Contribution to Sympathetic Vasomotor Tone of Tonic Glutamatergic Inputs to Neurons in the RVLM","volume":"287","author":"Horiuchi","year":"2004","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"973","DOI":"10.2174\/1381612053381684","article-title":"Blood-brain barrier transport of cytokines: A mechanism for neuropathology","volume":"11","author":"Banks","year":"2005","journal-title":"Curr. Pharm. Des."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1038\/nrn2297","article-title":"From inflammation to sickness and depression: When the immune system subjugates the brain","volume":"9","author":"Dantzer","year":"2008","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bbi.2016.03.010","article-title":"The blood-brain barrier in systemic inflammation","volume":"60","author":"Varatharaj","year":"2017","journal-title":"Brain Behav. Immun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1016\/j.bbi.2011.06.006","article-title":"Cytokine and chemokine responses in serum and brain after single and repeated injections of lipopolysaccharide: Multiplex quantification with path analysis","volume":"25","author":"Erickson","year":"2011","journal-title":"Brain Behav. Immun."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1535750","DOI":"10.1080\/20013078.2018.1535750","article-title":"Minimal information for studies of extracellular vesicles 2018 (MISEV2018): A position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines","volume":"7","author":"Witwer","year":"2018","journal-title":"J. Extracell. Vesicles"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Ridder, K., Keller, S., Dams, M., Rupp, A.-K., Schlaudraff, J., Del Turco, D., Starmann, J., Macas, J., Karpova, D., and Devraj, K. (2014). Extracellular vesicle-mediated transfer of genetic information between the hematopoietic system and the brain in response to inflammation. PLoS Biol., 12, Correction in PLoS Biol.\u00a02018, 16, e1002623. https:\/\/doi.org\/10.1371\/journal.pbio.1002623.","DOI":"10.1371\/journal.pbio.1001874"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1172\/JCI58644","article-title":"Innate immunity in the central nervous system","volume":"122","author":"Ransohoff","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/nri3705","article-title":"Innate immune activation in neurodegenerative disease","volume":"14","author":"Heneka","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1016\/j.immuni.2017.06.006","article-title":"Reactive Astrocytes: Production, Function, and Therapeutic Potential","volume":"46","author":"Liddelow","year":"2017","journal-title":"Immunity"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/j.it.2012.07.004","article-title":"Capture, crawl, cross: The T cell code to breach the blood-brain barriers","volume":"33","author":"Engelhardt","year":"2012","journal-title":"Trends Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1038\/nm1651","article-title":"Human TH17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation","volume":"13","author":"Kebir","year":"2007","journal-title":"Nat. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.1016\/j.jacc.2018.08.1043","article-title":"Inflammation, Immunity, and Infection in Atherothrombosis: JACC Review Topic of the Week","volume":"72","author":"Libby","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/nri3345","article-title":"Thrombosis as an intravascular effector of innate immunity","volume":"13","author":"Engelmann","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1016\/j.neuron.2013.10.008","article-title":"The pathobiology of vascular dementia","volume":"80","author":"Iadecola","year":"2013","journal-title":"Neuron"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"E4","DOI":"10.3171\/foc.2007.22.5.5","article-title":"Vasogenic edema due to tight junction disruption by matrix metalloproteinases in cerebral ischemia","volume":"22","author":"Rosenberg","year":"2007","journal-title":"Neurosurg. Focus"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1161\/01.CIR.99.10.1348","article-title":"Detection of adenoviral genome in the myocardium of adult patients with idiopathic left ventricular dysfunction","volume":"99","author":"Pauschinger","year":"1999","journal-title":"Circulation"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1161\/01.CIR.0000155615.68924.B3","article-title":"High prevalence of cardiac parvovirus B19 infection in patients with isolated left ventricular diastolic dysfunction","volume":"111","author":"Bock","year":"2005","journal-title":"Circulation"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1016\/j.hrthm.2020.05.001","article-title":"Recognizing COVID-19-Related Myocarditis: The Possible Pathophysiology and Proposed Guideline for Diagnosis and Management","volume":"17","author":"Siripanthong","year":"2020","journal-title":"Heart Rhythm"},{"key":"ref_65","first-page":"116","article-title":"Cardiovascular magnetic resonance findings in competitive athletes recovering from COVID-19 infection","volume":"6","author":"Rajpal","year":"2021","journal-title":"JAMA Cardiol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.gheart.2014.01.007","article-title":"The global burden of myocarditis: Part 1: A systematic literature review for the Global Burden of Diseases, Injuries, and Risk Factors 2010 study","volume":"9","author":"Cooper","year":"2014","journal-title":"Glob. Heart"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Li, J., Fan, H., Yang, Y., Huang, Z., Yuan, Y., and Liang, B. (2024). Global burden of myocarditis from 1990 to 2021: Findings from the Global Burden of Disease Study 2021. BMC Cardiovasc. Disord., 24.","DOI":"10.1186\/s12872-024-04402-z"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/s41593-024-01576-9","article-title":"Blood\u2013brain barrier disruption and sustained systemic inflammation in individuals with long COVID-associated cognitive impairment","volume":"27","author":"Greene","year":"2024","journal-title":"Nat. Neurosci."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Kelley, N., Jeltema, D., Duan, Y., and He, Y. (2019). The NLRP3 inflammasome: An overview of mechanisms of activation and regulation. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20133328"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e2234","DOI":"10.1038\/cddis.2016.140","article-title":"The emerging role of Toll-like receptor 4 in myocardial inflammation","volume":"7","author":"Yang","year":"2016","journal-title":"Cell Death Dis."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1113\/expphysiol.2012.068338","article-title":"The Nlrp3 inflammasome promotes myocardial dysfunction in structural cardiomyopathy through interleukin-1\u03b2","volume":"98","author":"Bracey","year":"2013","journal-title":"Exp. Physiol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1177\/0271678X18813317","article-title":"Inflammatory responses mediate brain\u2013heart interaction after ischemic stroke in adult mice","volume":"40","author":"Yan","year":"2020","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1016\/S0197-4580(01)00287-1","article-title":"Interleukin-1, neuroinflammation, and Alzheimer\u2019s disease","volume":"22","author":"Mrak","year":"2001","journal-title":"Neurobiol. Aging"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.7150\/ijbs.4989","article-title":"IL-6 trans-signaling via the soluble IL-6 receptor: Importance for the pro-inflammatory activities of IL-6","volume":"8","year":"2012","journal-title":"Int. J. Biol. Sci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.cytogfr.2015.07.004","article-title":"Interleukin-6: Biology, signaling and strategies of blockade","volume":"26","author":"Schaper","year":"2015","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_76","first-page":"6283","article-title":"IL-6 knockout ameliorates myocardial remodeling after myocardial infarction by regulating activation of M2 macrophages and fibroblast cells","volume":"23","author":"Jing","year":"2019","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1097\/00001573-199705000-00002","article-title":"The role of cytokines in disease progression in heart failure","volume":"12","author":"Shan","year":"1997","journal-title":"Curr. Opin. Cardiol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1873","DOI":"10.1093\/brain\/awg171","article-title":"Lack of IL-6 augments inflammatory response but decreases vascular permeability in bacterial meningitis","volume":"126","author":"Paul","year":"2003","journal-title":"Brain"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/nri.2016.123","article-title":"Cytokine networks in neuroinflammation","volume":"17","author":"Becher","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/s11886-000-0068-4","article-title":"The role of tumor necrosis factor alpha in the pathophysiology of congestive heart failure","volume":"2","author":"McTiernan","year":"2000","journal-title":"Curr. Cardiol. Rep."},{"key":"ref_81","first-page":"229","article-title":"Pathogenesis of inflammatory cardiomyopathies","volume":"93","author":"Schultheiss","year":"1998","journal-title":"Med. Klin."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"152706","DOI":"10.1016\/j.imbio.2023.152706","article-title":"TNF-\u03b1 evokes blood\u2013brain barrier dysfunction through activation of Rho-kinase and neurokinin 1 receptor","volume":"228","author":"Gao","year":"2023","journal-title":"Immunobiology"},{"key":"ref_83","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_84","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1111\/j.1574-695X.2011.00918.x","article-title":"Blockade of interleukin-17A protects against coxsackievirus B3-induced myocarditis by increasing COX-2\/PGE2 production in the heart","volume":"64","author":"Xie","year":"2012","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Sisto, M., and Lisi, S. (2023). Interleukin-23 involved in fibrotic autoimmune diseases: New discoveries. J. Clin. Med., 12.","DOI":"10.20944\/preprints202308.0534.v1"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1186\/1743-422X-8-301","article-title":"Expression of IL-23\/Th17 pathway in a murine model of coxsackie virus B3-induced viral myocarditis","volume":"8","author":"Yang","year":"2011","journal-title":"Virol. J."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"9309","DOI":"10.3892\/mmr.2017.7771","article-title":"Promoting effects of IL-23 on myocardial ischemia and reperfusion are associated with increased expression of IL-17A and upregulation of the JAK2\/STAT3 signaling pathway","volume":"16","author":"Liao","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.molimm.2016.04.003","article-title":"IL-17A promotes microglial activation and neuroinflammation in mouse models of intracerebral haemorrhage","volume":"73","author":"Yu","year":"2016","journal-title":"Mol. Immunol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/1476-9255-8-22","article-title":"Role of IL-33 in inflammation and disease","volume":"8","author":"Miller","year":"2011","journal-title":"J. Inflamm. Lond."},{"key":"ref_90","first-page":"2167","article-title":"Roles of IL-33 in the pathogenesis of cardiac disorders","volume":"248","author":"Jiang","year":"2023","journal-title":"Exp. Biol. Med."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/j.neuron.2015.01.013","article-title":"The glia-derived alarmin IL-33 orchestrates the immune response and promotes recovery following CNS injury","volume":"85","author":"Gadani","year":"2015","journal-title":"Neuron"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Ochs, M.J., Steinhilber, D., and Suess, B. (2011). MicroRNA involved in inflammation: Control of eicosanoid pathway. Front. Pharmacol., 2.","DOI":"10.3389\/fphar.2011.00039"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1093\/intimm\/dxr034","article-title":"A trio of microRNAs that control Toll-like receptor signalling","volume":"23","author":"Quinn","year":"2011","journal-title":"Int. Immunol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2551","DOI":"10.1096\/fj.13-248880","article-title":"MicroRNA-155 negatively affects blood\u2013brain barrier function during neuroinflammation","volume":"28","author":"Wu","year":"2014","journal-title":"FASEB J."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1038\/leu.2011.356","article-title":"MicroRNAs in inflammation and immune responses","volume":"26","author":"Contreras","year":"2012","journal-title":"Leukemia"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1038\/nature07511","article-title":"MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts","volume":"456","author":"Thum","year":"2008","journal-title":"Nature"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1038\/nrneurol.2013.67","article-title":"The emerging roles of microRNAs in CNS injuries","volume":"9","author":"Bhalala","year":"2013","journal-title":"Nat. Rev. Neurol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.devcel.2008.07.008","article-title":"miR-126 regulates angiogenic signaling and vascular integrity","volume":"15","author":"Fish","year":"2008","journal-title":"Dev. Cell"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"4175","DOI":"10.4049\/jimmunol.1201516","article-title":"NLRP3 inflammasome activity is negatively controlled by miR-223","volume":"189","author":"Bauernfeind","year":"2012","journal-title":"J. Immunol."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Ren, J., Liu, W., Jin, X., Zhang, C., Xu, X., Deng, G., Gao, X., Li, J., Li, R., and Zhang, X. (2025). Global, Regional, and National Burden of Myocarditis and Its Attributable Risk Factors in 204 Countries and Territories from 1990 to 2021: Updated Systematic Analysis. Front. Public Health, 13.","DOI":"10.3389\/fpubh.2025.1542921"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1152\/physrev.00050.2017","article-title":"Blood\u2013Brain Barrier: From Physiology to Disease and Back","volume":"99","author":"Sweeney","year":"2019","journal-title":"Physiol. Rev."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1007\/s00401-018-1812-4","article-title":"The Role of Brain Barriers in Fluid Movement in the CNS: Is There a \u201cGlymphatic\u201d System?","volume":"135","author":"Abbott","year":"2018","journal-title":"Acta Neuropathol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.devcel.2011.07.001","article-title":"Pericytes: Developmental, Physiological, and Pathological Perspectives, Problems, and Promises","volume":"21","author":"Armulik","year":"2011","journal-title":"Dev. Cell"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1189\/jlb.70.2.192","article-title":"IL-1 and TNF Independent Pathways Mediate ICAM-1\/VCAM-1 Up-Regulation in Ischemia Reperfusion Injury","volume":"70","author":"Burne","year":"2001","journal-title":"J. Leukoc. Biol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1684\/ecn.2024.0498","article-title":"Effect of Proinflammatory Cytokines on Blood\u2013Brain Barrier Integrity","volume":"35","author":"Grabowska","year":"2024","journal-title":"Eur. Cytokine Netw."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Furutama, D., Matsuda, S., Yamawaki, Y., Hatano, S., Okanobu, A., Memida, T., Oue, H., Fujita, T., Ouhara, K., and Kajiya, M. (2020). IL-6 Induced by Periodontal Inflammation Causes Neuroinflammation and Disrupts the Blood\u2013Brain Barrier. Brain Sci., 10.","DOI":"10.3390\/brainsci10100679"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1111\/j.1755-5949.2012.00340.x","article-title":"Tight Junction in Blood\u2013Brain Barrier: An Overview of Structure, Regulation, and Regulator Substances","volume":"18","author":"Liu","year":"2012","journal-title":"CNS Neurosci. Ther."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"21796","DOI":"10.1002\/jcp.28942","article-title":"Circulating Exosomal miRNAs in Cardiovascular Disease Pathogenesis: New Emerging Hopes","volume":"234","author":"Aghabozorgi","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1056\/NEJMoa1707914","article-title":"Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease","volume":"377","author":"Ridker","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Caldarelli, M., Franza, L., Cutrupi, S., Menegolo, M., Franceschi, F., Gasbarrini, A., Gambassi, G., and Cianci, R. (2025). Inflammasomes in Cardiovascular Diseases: Current Knowledge and Future Perspectives. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26125439"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/s12987-024-00557-1","article-title":"Cellular and Molecular Mechanisms of the Blood\u2013Brain Barrier Dysfunction in Neurodegenerative Diseases","volume":"21","author":"Chen","year":"2024","journal-title":"Fluids Barriers CNS"},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Uccello, G., Bonacchi, G., Rossi, V.A., Montrasio, G., and Beltrami, M. (2024). Myocarditis and Chronic Inflammatory Cardiomyopathy, from Acute Inflammation to Chronic Inflammatory Damage: An Update on Pathophysiology and Diagnosis. J. Clin. Med., 13.","DOI":"10.3390\/jcm13010150"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.1161\/01.CIR.0000124490.27666.B2","article-title":"Targeted Anticytokine Therapy in Patients with Chronic Heart Failure: Results of the Randomized Etanercept Worldwide Evaluation (RENEWAL)","volume":"109","author":"Mann","year":"2004","journal-title":"Circulation"},{"key":"ref_114","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_115","doi-asserted-by":"crossref","unstructured":"Mezzaroma, E., Abbate, A., and Toldo, S. (2021). NLRP3 Inflammasome Inhibitors in Cardiovascular Diseases. Molecules, 26.","DOI":"10.3390\/molecules26040976"},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Das, K., and Rao, L.V.M. (2022). The Role of microRNAs in Inflammation. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232415479"},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Lochhead, J.J., Yang, J., Ronaldson, P.T., and Davis, T.P. (2020). Structure, Function, and Regulation of the Blood\u2013Brain Barrier Tight Junction in Central Nervous System Disorders. Front. Physiol., 11.","DOI":"10.3389\/fphys.2020.00914"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1038\/nbt.1807","article-title":"Delivery of siRNA to the Mouse Brain by Systemic Injection of Targeted Exosomes","volume":"29","author":"Seow","year":"2011","journal-title":"Nat. Biotechnol."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Hwang, J.S., Vo, T.T.L., Kim, M., Cha, E.H., Mun, K.C., Ha, E., and Seo, J.H. (2025). Involvement of RhoA\/ROCK Signaling Pathway in Methamphetamine-Induced Blood\u2013Brain Barrier Disruption. Biomolecules, 15.","DOI":"10.3390\/biom15030340"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1016\/j.cell.2012.10.042","article-title":"Norrin\/Frizzled4 Signaling in Retinal Vascular Development and Blood\u2013Brain Barrier Plasticity","volume":"151","author":"Wang","year":"2012","journal-title":"Cell"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1038\/jcbfm.2009.194","article-title":"Minocycline Reduces Neuronal Death and Attenuates Microglial Response after Pediatric Asphyxial Cardiac Arrest","volume":"30","author":"Tang","year":"2010","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1016\/j.jacbts.2023.03.025","article-title":"Vagal Nerve Stimulation Reduces Ventricular Arrhythmias and Mitigates Adverse Neural Cardiac Remodeling Post-Myocardial Infarction","volume":"8","author":"Hadaya","year":"2023","journal-title":"JACC Basic Transl. Sci."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1995","DOI":"10.1093\/eurheartj\/ehp249","article-title":"Randomized study on the efficacy of immunosuppressive therapy in patients with virus-negative inflammatory cardiomyopathy: The TIMIC study","volume":"30","author":"Frustaci","year":"2009","journal-title":"Eur. Heart J."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.1093\/eurheartj\/ehy128","article-title":"Interleukin-1 blockade in cardiovascular diseases: A clinical update","volume":"39","author":"Buckley","year":"2018","journal-title":"Eur. Heart J."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"e007405","DOI":"10.1161\/CIRCHEARTFAILURE.120.007405","article-title":"Management of acute myocarditis and chronic inflammatory cardiomyopathy: An expert consensus document","volume":"13","author":"Ammirati","year":"2020","journal-title":"Circ. Heart Fail."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/6\/2603\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T05:25:30Z","timestamp":1773465930000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/6\/2603"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,12]]},"references-count":125,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["ijms27062603"],"URL":"https:\/\/doi.org\/10.3390\/ijms27062603","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,12]]}}}