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image of Myocardial Inflammation as Key Mediator of Heart-brain Interaction After Myocardial Ischemia/Infarction: Mechanistic Exploration of Post-Myocardial Infarction Cognitive Dysfunction

Abstract

Myocardial Infarction (MI) is a severe cardiovascular event, causing not only substantial damage to the heart but also potentially exerting a profound impact on brain function through a complex cardiac-brain interaction mechanism. The pathological process of MI encompasses myocardial cell necrosis, inflammatory cell infiltration, and the release of a substantial amount of inflammatory mediators. Through the bloodstream, these myocardial mediators may traverse the Blood-Brain Barrier (BBB), eliciting a neuroinflammatory response that can lead to cognitive dysfunction. This article proposes a critical research direction: investigating whether MI mediates the effects of myocardial-derived mediators on the permeability of the BBB, as well as the potential consequences of these mediators on cognitive functions. This review is aimed at triggering future research to elucidate the underlying mechanisms governing heart-brain interactions after MI in order to facilitate the development of more effective cognitive protection strategies for patients with MI.

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2025-09-15
2025-11-04

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References

  1. Kasprzak D. Kaczmarek-Majer K. Rzeźniczak J. Klamecka-Pohl K. Ganowicz-Kaatz T. Słomczyński M. Budzianowski J. Pieszko K. Hiczkiewicz J. Tykarski A. Burchardt P. Cognitive impairment in cardiovascular patients after myocardial infarction: Prospective clinical study. J. Clin. Med. 2023 12 15 4954 10.3390/jcm12154954 37568355
    [Google Scholar]
  2. Zhang J. Xie L. Cheng C. Liu Y. Zhang X. Wang H. Hu J. Yu H. Xu J. Hippocampal subfield volumes in mild cognitive impairment and alzheimer’s disease: A systematic review and meta-analysis. Brain Imaging Behav. 2023 17 6 778 793 10.1007/s11682‑023‑00804‑3 37768441
    [Google Scholar]
  3. Frey A. Homola G.A. Henneges C. Mühlbauer L. Sell R. Kraft P. Franke M. Morbach C. Vogt M. Müllges W. Ertl G. Solymosi L. Pirpamer L. Schmidt R. Pham M. Störk S. Stoll G. Temporal changes in total and hippocampal brain volume and cognitive function in patients with chronic heart failure—the COGNITION.MATTERS-HF cohort study. Eur. Heart J. 2021 42 16 1569 1578 10.1093/eurheartj/ehab003 33496311
    [Google Scholar]
  4. Byron-Alhassan A. Tulloch H.E. Collins B. Quinlan B. Fang Z. Chakraborty S. Le May M. Duchesne L. Smith A.M. Exploratory analyses of cerebral gray matter volumes after out-of-hospital cardiac arrest in good outcome survivors. Front. Psychol. 2020 11 856 10.3389/fpsyg.2020.00856 32435222
    [Google Scholar]
  5. Paraskevas K.I. Mikhailidis D.P. Spinelli F. Faggioli G. Saba L. Silvestrini M. Svetlikov A. Stilo F. Pini R. Myrcha P. Di Lazzaro V. Antignani P.L. Poredos P. Lanza G. Asymptomatic carotid stenosis and cognitive impairment. J. Cardiovasc. Surg. 2023 64 2 167 173 10.23736/S0021‑9509.23.12620‑6 36790142
    [Google Scholar]
  6. Shen L. Dewan P. Ferreira J.P. Cunningham J.W. Jhund P.S. Anand I.S. Chandra A. Chiang L.M. Claggett B. Desai A.S. Gong J. Lam C.S.P. Lefkowitz M.P. Maggioni A.P. Martinez F. Packer M. Redfield M.M. Rouleau J.L. van Veldhuisen D.J. Zannad F. Zile M.R. Solomon S.D. McMurray J.J.V. Clinical correlates and prognostic impact of cognitive dysfunction in patients with heart failure and preserved ejection fraction: Insights from parAGON-HF. Circulation 2024 150 24 1913 1927 10.1161/CIRCULATIONAHA.124.070553 39429145
    [Google Scholar]
  7. Sies H. Berndt C. Jones D.P. Oxidative Stress. Annu. Rev. Biochem. 2017 86 1 715 748 10.1146/annurev‑biochem‑061516‑045037 28441057
    [Google Scholar]
  8. Ramachandra C.J.A. Hernandez-Resendiz S. Crespo-Avilan G.E. Lin Y.H. Hausenloy D.J. Mitochondria in acute myocardial infarction and cardioprotection. EBioMedicine 2020 57 102884 10.1016/j.ebiom.2020.102884 32653860
    [Google Scholar]
  9. Jakubczyk K. Dec K. Kałduńska J. Kawczuga D. Kochman J. Janda K. Reactive oxygen species - sources, functions, oxidative damage. Pol. Merkuriusz Lek. 2020 48 284 124 127 32352946
    [Google Scholar]
  10. Aviello G. Knaus U.G. NADPH oxidases and ROS signaling in the gastrointestinal tract. Mucosal Immunol. 2018 11 4 1011 1023 10.1038/s41385‑018‑0021‑8 29743611
    [Google Scholar]
  11. Carbone F. Bonaventura A. Montecucco F. Neutrophil-related oxidants drive heart and brain remodeling after ischemia/] reperfusion injury. Front. Physiol. 2020 10 1587 10.3389/fphys.2019.01587 32116732
    [Google Scholar]
  12. Bugger H. Pfeil K. Mitochondrial ROS in myocardial ischemia reperfusion and remodeling. Biochim. Biophys. Acta Mol. Basis Dis. 2020 1866 7 165768 10.1016/j.bbadis.2020.165768 32173461
    [Google Scholar]
  13. Görlach A. Bertram K. Hudecova S. Krizanova O. Calcium and ROS: A mutual interplay. Redox Biol. 2015 6 260 271 10.1016/j.redox.2015.08.010 26296072
    [Google Scholar]
  14. Webster K.A. Mitochondrial membrane permeabilization and cell death during myocardial infarction: Roles of calcium and reactive oxygen species. Future Cardiol. 2012 8 6 863 884 10.2217/fca.12.58 23176689
    [Google Scholar]
  15. Moris D. Spartalis M. Tzatzaki E. Spartalis E. Karachaliou G.S. Triantafyllis A.S. Karaolanis G.I. Tsilimigras D.I. Theocharis S. The role of reactive oxygen species in myocardial redox signaling and regulation. Ann. Transl. Med. 2017 5 16 324 10.21037/atm.2017.06.17 28861421
    [Google Scholar]
  16. Frangogiannis N.G. The inflammatory response in myocardial injury, repair, and remodelling. Nat. Rev. Cardiol. 2014 11 5 255 265 10.1038/nrcardio.2014.28 24663091
    [Google Scholar]
  17. van Hout G.P.J. Arslan F. Pasterkamp G. Hoefer I.E. Targeting danger-associated molecular patterns after myocardial infarction. Expert Opin. Ther. Targets 2016 20 2 223 239 10.1517/14728222.2016.1088005 26420647
    [Google Scholar]
  18. Timmers L. Sluijter J.P.G. van Keulen J.K. Hoefer I.E. Nederhoff M.G.J. Goumans M.J. Doevendans P.A. van Echteld C.J.A. Joles J.A. Quax P.H. Piek J.J. Pasterkamp G. de Kleijn D.P.V. Toll-like receptor 4 mediates maladaptive left ventricular remodeling and impairs cardiac function after myocardial infarction. Circ. Res. 2008 102 2 257 264 10.1161/CIRCRESAHA.107.158220 18007026
    [Google Scholar]
  19. Shishido T. Nozaki N. Yamaguchi S. Shibata Y. Nitobe J. Miyamoto T. Takahashi H. Arimoto T. Maeda K. Yamakawa M. Takeuchi O. Akira S. Takeishi Y. Kubota I. Toll-like receptor-2 modulates ventricular remodeling after myocardial infarction. Circulation 2003 108 23 2905 2910 10.1161/01.CIR.0000101921.93016.1C 14656915
    [Google Scholar]
  20. Shimamoto A. Chong A.J. Yada M. Shomura S. Takayama H. Fleisig A.J. Agnew M.L. Hampton C.R. Rothnie C.L. Spring D.J. Pohlman T.H. Shimpo H. Verrier E.D. Inhibition of Toll-like receptor 4 with eritoran attenuates myocardial ischemia-reperfusion injury. Circulation 2006 114 (1_supplement) I270 I274 10.1161/CIRCULATIONAHA.105.000901 16820585
    [Google Scholar]
  21. Arslan F. Smeets M.B. O’Neill L.A.J. Keogh B. McGuirk P. Timmers L. Tersteeg C. Hoefer I.E. Doevendans P.A. Pasterkamp G. de Kleijn D.P.V. Myocardial ischemia/reperfusion injury is mediated by leukocytic toll-like receptor-2 and reduced by systemic administration of a novel anti-toll-like receptor-2 antibody. Circulation 2010 121 1 80 90 10.1161/CIRCULATIONAHA.109.880187 20026776
    [Google Scholar]
  22. Wang F. Gong Y. Chen T. Li B. Zhang W. Yin L. Zhao H. Tang Y. Wang X. Huang C. Maresin1 ameliorates ventricular remodelling and arrhythmia in mice models of myocardial infarction via NRF2/HO-1 and TLR4/NF-kB signalling. Int. Immunopharmacol 2022 113 Pt A 109369 10.1016/j.intimp.2022.109369
    [Google Scholar]
  23. Oyama J. Blais C. Liu X. Pu M. Kobzik L. Kelly R.A. Bourcier T. Reduced myocardial ischemia-reperfusion injury in toll-like receptor 4-deficient mice. Circulation 2004 109 6 784 789 10.1161/01.CIR.0000112575.66565.84 14970116
    [Google Scholar]
  24. Toldo S. Abbate A. The NLRP3 inflammasome in acute myocardial infarction. Nat. Rev. Cardiol. 2018 15 4 203 214 10.1038/nrcardio.2017.161 29143812
    [Google Scholar]
  25. Fujisue K. Sugamura K. Kurokawa H. Matsubara J. Ishii M. Izumiya Y. Kaikita K. Sugiyama S. Colchicine improves survival, left ventricular remodeling, and chronic cardiac function after acute myocardial infarction. Circ. J. 2017 81 8 1174 1182 10.1253/circj.CJ‑16‑0949 28420825
    [Google Scholar]
  26. Akodad M. Fauconnier J. Sicard P. Huet F. Blandel F. Bourret A. de Santa Barbara P. Aguilhon S. LeGall M. Hugon G. Lacampagne A. Roubille F. Interest of colchicine in the treatment of acute myocardial infarct responsible for heart failure in a mouse model. Int. J. Cardiol. 2017 240 347 353 10.1016/j.ijcard.2017.03.126 28395979
    [Google Scholar]
  27. Martinon F. Pétrilli V. Mayor A. Tardivel A. Tschopp J. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 2006 440 7081 237 241 10.1038/nature04516 16407889
    [Google Scholar]
  28. Kim Y.S. Kim J.S. Kwon J.S. Jeong M.H. Cho J.G. Park J.C. Kang J.C. Ahn Y. BAY 11-7082, a nuclear factor-κB inhibitor, reduces inflammation and apoptosis in a rat cardiac ischemia-reperfusion injury model. Int. Heart J. 2010 51 5 348 353 10.1536/ihj.51.348 20966608
    [Google Scholar]
  29. Coll R.C. Robertson A.A.B. Chae J.J. Higgins S.C. Muñoz-Planillo R. Inserra M.C. Vetter I. Dungan L.S. Monks B.G. Stutz A. Croker D.E. Butler M.S. Haneklaus M. Sutton C.E. Núñez G. Latz E. Kastner D.L. Mills K.H.G. Masters S.L. Schroder K. Cooper M.A. O’Neill L.A.J. A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases. Nat. Med. 2015 21 3 248 255 10.1038/nm.3806 25686105
    [Google Scholar]
  30. Toldo S. Marchetti C. Mauro A.G. Chojnacki J. Mezzaroma E. Carbone S. Zhang S. Van Tassell B. Salloum F.N. Abbate A. Inhibition of the NLRP3 inflammasome limits the inflammatory injury following myocardial ischemia-reperfusion in the mouse. Int. J. Cardiol. 2016 209 215 220 10.1016/j.ijcard.2016.02.043 26896627
    [Google Scholar]
  31. Timmers L. Pasterkamp G. de Hoog V.C. Arslan F. Appelman Y. de Kleijn D.P.V. The innate immune response in reperfused myocardium. Cardiovasc. Res. 2012 94 2 276 283 10.1093/cvr/cvs018 22266751
    [Google Scholar]
  32. Weisman H.F. Bartow T. Leppo M.K. Marsh H.C. Carson G.R. Concino M.F. Boyle M.P. Roux K.H. Weisfeldt M.L. Fearon D.T. Soluble human complement receptor type 1: In vivo inhibitor of complement suppressing post-ischemic myocardial inflammation and necrosis. Science 1990 249 4965 146 151 10.1126/science.2371562 2371562
    [Google Scholar]
  33. Buerke M. Murohara T. Lefer A.M. Cardioprotective effects of a C1 esterase inhibitor in myocardial ischemia and reperfusion. Circulation 1995 91 2 393 402 10.1161/01.CIR.91.2.393 7805243
    [Google Scholar]
  34. Walsh M.C. Bourcier T. Takahashi K. Shi L. Busche M.N. Rother R.P. Solomon S.D. Ezekowitz R.A.B. Stahl G.L. Mannose-binding lectin is a regulator of inflammation that accompanies myocardial ischemia and reperfusion injury. J. Immunol. 2005 175 1 541 546 10.4049/jimmunol.175.1.541 15972690
    [Google Scholar]
  35. Mueller M. Herzog C. Larmann J. Schmitz M. Hilfiker-Kleiner D. Gessner J.E. Theilmeier G. The receptor for activated complement factor 5 (C5aR) conveys myocardial ischemic damage by mediating neutrophil transmigration. Immunobiology 2013 218 9 1131 1138 10.1016/j.imbio.2013.03.006 23642836
    [Google Scholar]
  36. De Hoog V.C. Timmers L. Van Duijvenvoorde A. De Jager S.C.A. Van Middelaar B.J. Smeets M.B. Woodruff T.M. Doevendans P.A. Pasterkamp G. Hack C.E. De Kleijn D.P.V. Leucocyte expression of complement C5a receptors exacerbates infarct size after myocardial reperfusion injury. Cardiovasc. Res. 2014 103 4 521 529 10.1093/cvr/cvu153 24935433
    [Google Scholar]
  37. Hilgendorf I. Frantz S. Frangogiannis N.G. Repair of the infarcted heart: Cellular effectors, molecular mechanisms and therapeutic opportunities. Circ. Res. 2024 134 12 1718 1751 10.1161/CIRCRESAHA.124.323658 38843294
    [Google Scholar]
  38. Horckmans M. Ring L. Duchene J. Santovito D. Schloss M.J. Drechsler M. Weber C. Soehnlein O. Steffens S. Neutrophils orchestrate post-myocardial infarction healing by polarizing macrophages towards a reparative phenotype. Eur. Heart J. 2016 38 3 ehw002 10.1093/eurheartj/ehw002 28158426
    [Google Scholar]
  39. Ma Y. Yabluchanskiy A. Iyer R.P. Cannon P.L. Flynn E.R. Jung M. Henry J. Cates C.A. Deleon-Pennell K.Y. Lindsey M.L. Temporal neutrophil polarization following myocardial infarction. Cardiovasc. Res. 2016 110 1 51 61 10.1093/cvr/cvw024 26825554
    [Google Scholar]
  40. Jian Y. Zhou X. Shan W. Chen C. Ge W. Cui J. Yi W. Sun Y. Crosstalk between macrophages and cardiac cells after myocardial infarction. Cell Commun. Signal. 2023 21 1 109 10.1186/s12964‑023‑01105‑4 37170235
    [Google Scholar]
  41. Courties G. Heidt T. Sebas M. Iwamoto Y. Jeon D. Truelove J. Tricot B. Wojtkiewicz G. Dutta P. Sager H.B. Borodovsky A. Novobrantseva T. Klebanov B. Fitzgerald K. Anderson D.G. Libby P. Swirski F.K. Weissleder R. Nahrendorf M. In vivo silencing of the transcription factor IRF5 reprograms the macrophage phenotype and improves infarct healing. J. Am. Coll. Cardiol. 2014 63 15 1556 1566 10.1016/j.jacc.2013.11.023 24361318
    [Google Scholar]
  42. Harel-Adar T. Mordechai T.B. Amsalem Y. Feinberg M.S. Leor J. Cohen S. Modulation of cardiac macrophages by phosphatidylserine-presenting liposomes improves infarct repair. Proc. Natl. Acad. Sci. USA 2011 108 5 1827 1832 10.1073/pnas.1015623108 21245355
    [Google Scholar]
  43. Leuschner F. Dutta P. Gorbatov R. Novobrantseva T.I. Donahoe J.S. Courties G. Lee K.M. Kim J.I. Markmann J.F. Marinelli B. Panizzi P. Lee W.W. Iwamoto Y. Milstein S. Epstein-Barash H. Cantley W. Wong J. Cortez-Retamozo V. Newton A. Love K. Libby P. Pittet M.J. Swirski F.K. Koteliansky V. Langer R. Weissleder R. Anderson D.G. Nahrendorf M. Therapeutic siRNA silencing in inflammatory monocytes in mice. Nat. Biotechnol. 2011 29 11 1005 1010 10.1038/nbt.1989 21983520
    [Google Scholar]
  44. Ben-Mordechai T. Holbova R. Landa-Rouben N. Harel-Adar T. Feinberg M.S. Abd Elrahman I. Blum G. Epstein F.H. Silman Z. Cohen S. Leor J. Macrophage subpopulations are essential for infarct repair with and without stem cell therapy. J. Am. Coll. Cardiol. 2013 62 20 1890 1901 10.1016/j.jacc.2013.07.057 23973704
    [Google Scholar]
  45. Shao Y. Li Y. Liu Y. Zhu S. Wu J. Ma K. Li G. Huang S. Wen H. Zhang C. Ma X. Li P. Du J. Li Y. ATF3 coordinates the survival and proliferation of cardiac macrophages and protects against ischemia-reperfusion injury. Nat. Cardiovasc. Res. 2024 3 1 28 45 10.1038/s44161‑023‑00392‑x 39195894
    [Google Scholar]
  46. Shook P.L. Singh M. Singh K. Macrophages in the inflammatory phase following myocardial infarction: Role of exogenous ubiquitin. Biology (Basel) 2023 12 9 1258 10.3390/biology12091258 37759657
    [Google Scholar]
  47. Nian W. Huang Z. Fu C. Immune cells drive new immunomodulatory therapies for myocardial infarction: From basic to clinical translation. Front. Immunol. 2023 14 1097295 10.3389/fimmu.2023.1097295 36761726
    [Google Scholar]
  48. Timmermans A.D. Balteau M. Gélinas R. Renguet E. Ginion A. de Meester C. Sakamoto K. Balligand J.L. Bontemps F. Vanoverschelde J.L. Horman S. Beauloye C. Bertrand L. A-769662 potentiates the effect of other AMP-activated protein kinase activators on cardiac glucose uptake. Am. J. Physiol. Heart Circ. Physiol. 2014 306 12 H1619 H1630 10.1152/ajpheart.00965.2013 24748590
    [Google Scholar]
  49. Ussher J.R. Wang W. Gandhi M. Keung W. Samokhvalov V. Oka T. Wagg C.S. Jaswal J.S. Harris R.A. Clanachan A.S. Dyck J.R.B. Lopaschuk G.D. Stimulation of glucose oxidation protects against acute myocardial infarction and reperfusion injury. Cardiovasc. Res. 2012 94 2 359 369 10.1093/cvr/cvs129 22436846
    [Google Scholar]
  50. Aziz F. Tripolt N.J. Pferschy P.N. Scharnagl H. Abdellatif M. Oulhaj A. Benedikt M. Kolesnik E. von Lewinski D. Sourij H. Ketone body levels and its associations with cardiac markers following an acute myocardial infarction: A post hoc analysis of the EMMY trial. Cardiovasc. Diabetol. 2024 23 1 145 10.1186/s12933‑024‑02221‑2 38678253
    [Google Scholar]
  51. Lauzier B. Vaillant F. Merlen C. Gélinas R. Bouchard B. Rivard M.E. Labarthe F. Dolinsky V.W. Dyck J.R.B. Allen B.G. Chatham J.C. Des Rosiers C. Metabolic effects of glutamine on the heart: Anaplerosis versus the hexosamine biosynthetic pathway. J. Mol. Cell. Cardiol. 2013 55 92 100 10.1016/j.yjmcc.2012.11.008 23201305
    [Google Scholar]
  52. Mihanfar A. Nejabati H.R. Fattahi A. latifi, Z.; Faridvand, Y.; Pezeshkian, M.; Jodati, A.R.; Safaie, N.; Afrasiabi, A.; Nouri, M. SIRT3-mediated cardiac remodeling/repair following myocardial infarction. Biomed. Pharmacother. 2018 108 367 373 10.1016/j.biopha.2018.09.079 30227330
    [Google Scholar]
  53. Bernardi P. Gerle C. Halestrap A.P. Jonas E.A. Karch J. Mnatsakanyan N. Pavlov E. Sheu S.S. Soukas A.A. Identity, structure, and function of the mitochondrial permeability transition pore: Controversies, consensus, recent advances, and future directions. Cell Death Differ. 2023 30 8 1869 1885 10.1038/s41418‑023‑01187‑0 37460667
    [Google Scholar]
  54. Mouton A.J. Aitken N.M. Moak S.P. do Carmo J.M. da Silva A.A. Omoto A.C.M. Li X. Wang Z. Schrimpe-Rutledge A.C. Codreanu S.G. Sherrod S.D. McLean J.A. Hall J.E. Temporal changes in glucose metabolism reflect polarization in resident and monocyte-derived macrophages after myocardial infarction. Front. Cardiovasc. Med. 2023 10 1136252 10.3389/fcvm.2023.1136252 37215542
    [Google Scholar]
  55. Vermeulen R.P. Hoekstra M. Nijsten M.W.N. van der Horst I.C. van Pelt L.J. Jessurun G.A. Jaarsma T. Zijlstra F. van den Heuvel A.F. Clinical correlates of arterial lactate levels in patients with ST-segment elevation myocardial infarction at admission: A descriptive study. Crit. Care 2010 14 5 R164 10.1186/cc9253 20825687
    [Google Scholar]
  56. Mavrić Ž. Zaputović L. Žagar D. Matana A. Smokvina D. Usefulness of blood lactate as a predictor of shock development in acute myocardial infarction. Am. J. Cardiol. 1991 67 7 565 568 10.1016/0002‑9149(91)90892‑O 2000787
    [Google Scholar]
  57. Gabriel-Costa D. Cunha T.F. Paixão N.A. Fortunato R.S. Rego-Monteiro I.C.C. Barreto-Chaves M.L.M. Brum P.C. Lactate-upregulation of lactate oxidation complex-related genes is blunted in left ventricle of myocardial infarcted rats. Braz. J. Med. Biol. Res. 2018 51 11 e7660 10.1590/1414‑431x20187660 30304133
    [Google Scholar]
  58. Wang N. Wang W. Wang X. Mang G. Chen J. Yan X. Tong Z. Yang Q. Wang M. Chen L. Sun P. Yang Y. Cui J. Yang M. Zhang Y. Wang D. Wu J. Zhang M. Yu B. Histone lactylation boosts reparative gene activation post-myocardial infarction. Circ. Res. 2022 131 11 893 908 10.1161/CIRCRESAHA.122.320488 36268709
    [Google Scholar]
  59. Fan M. Yang K. Wang X. Chen L. Gill P.S. Ha T. Liu L. Lewis N.H. Williams D.L. Li C. Lactate promotes endothelial-to-mesenchymal transition via Snail1 lactylation after myocardial infarction. Sci. Adv. 2023 9 5 eadc9465 10.1126/sciadv.adc9465 36735787
    [Google Scholar]
  60. Ferrero J.M. Gonzalez-Ascaso A. Matas J.F.R. The mechanisms of potassium loss in acute myocardial ischemia: New insights from computational simulations. Front. Physiol. 2023 14 1074160 10.3389/fphys.2023.1074160 36923288
    [Google Scholar]
  61. Kosuru R. Cai Y. Kandula V. Yan D. Wang C. Zheng H. Li Y. Irwin M.G. Singh S. Xia Z. AMPK contributes to cardioprotective effects of pterostilbene against myocardial ischemia- reperfusion injury in diabetic rats by suppressing cardiac oxidative stress and apoptosis. Cell. Physiol. Biochem. 2018 46 4 1381 1397 10.1159/000489154 29689567
    [Google Scholar]
  62. Dong Y. Chen H. Gao J. Liu Y. Li J. Wang J. Molecular machinery and interplay of apoptosis and autophagy in coronary heart disease. J. Mol. Cell. Cardiol. 2019 136 27 41 10.1016/j.yjmcc.2019.09.001 31505198
    [Google Scholar]
  63. Oyadomari S. Mori M. Roles of CHOP/GADD153 in endoplasmic reticulum stress. Cell Death Differ. 2004 11 4 381 389 10.1038/sj.cdd.4401373 14685163
    [Google Scholar]
  64. Wang M. Zhang J. Yin Z. Ding W. Zhao M. Liu J. Xu Y. Xu S. Pan W. Wei C. Jiang H. Wan J. Microglia‐mediated neuroimmune response regulates cardiac remodeling after myocardial infarction. J. Am. Heart Assoc. 2023 12 12 e029053 10.1161/JAHA.122.029053 37318008
    [Google Scholar]
  65. Chen A.Q. Fang Z. Chen X.L. Yang S. Zhou Y.F. Mao L. Xia Y.P. Jin H.J. Li Y.N. You M.F. Wang X.X. Lei H. He Q.W. Hu B. Microglia-derived TNF-α mediates endothelial necroptosis aggravating blood brain-barrier disruption after ischemic stroke. Cell Death Dis. 2019 10 7 487 10.1038/s41419‑019‑1716‑9 31221990
    [Google Scholar]
  66. Sarver D.C. Lusis A.J. Linking the brain to recovery after myocardial infarction. Nat. Cardiovasc Res. 2024 3 7 780 781 10.1038/s44161‑024‑00497‑x 39196182
    [Google Scholar]
  67. Shaw B.C. Anders V.R. Tinkey R.A. Habean M.L. Brock O.D. Frostino B.J. Williams J.L. 2023
  68. Yang Y. Rosenberg G.A. Blood-brain barrier breakdown in acute and chronic cerebrovascular disease. Stroke 2011 42 11 3323 3328 10.1161/STROKEAHA.110.608257 21940972
    [Google Scholar]
  69. Nitta T. Hata M. Gotoh S. Seo Y. Sasaki H. Hashimoto N. Furuse M. Tsukita S. Size-selective loosening of the blood-brain barrier in claudin-5-deficient mice. J. Cell Biol. 2003 161 3 653 660 10.1083/jcb.200302070 12743111
    [Google Scholar]
  70. Yu Y. Weiss R.M. Wei S.G. Interleukin 17A contributes to blood‐brain barrier disruption of hypothalamic paraventricular nucleus in rats with myocardial infarction. J. Am. Heart Assoc. 2024 13 3 e032533 10.1161/JAHA.123.032533 38240234
    [Google Scholar]
  71. Liu H. Luiten P.G.M. Eisel U.L.M. Dejongste M.J.L. Schoemaker R.G. Depression after myocardial infarction: TNF-α-induced alterations of the blood-brain barrier and its putative therapeutic implications. Neurosci. Biobehav. Rev. 2013 37 4 561 572 10.1016/j.neubiorev.2013.02.004 23415700
    [Google Scholar]
  72. Yang Y. Chen J. Zhou J. Zhou D. Zhang A. Jiang Y. Lin J. Xia W. Cai Y. Han R. Lu Y. Liu D. Xia Z. Connexin43 overexpression promoted ferroptosis and increased myocardial vulnerability to ischemia-reperfusion injury in type 1 diabetic mice. Int. J. Med. Sci. 2024 21 12 2365 2378 10.7150/ijms.95170 39310260
    [Google Scholar]
  73. Wahid A. Wen J. Yang Q. Zhang Z. Zhao X. Tang X. Serum HMGB1 is a biomarker for acute myocardial infarction with or without heart failure. Clin. Transl. Sci. 2023 16 11 2299 2309 10.1111/cts.13630 37775976
    [Google Scholar]
  74. Foglio E. Pellegrini L. Russo M.A. Limana F. HMGB1-Mediated activation of the inflammatory-reparative response following myocardial infarction. Cells 2022 11 2 216 10.3390/cells11020216 35053332
    [Google Scholar]
  75. Raucci A. Di Maggio S. Scavello F. D’Ambrosio A. Bianchi M.E. Capogrossi M.C. The Janus face of HMGB1 in heart disease: A necessary update. Cell. Mol. Life Sci. 2019 76 2 211 229 10.1007/s00018‑018‑2930‑9 30306212
    [Google Scholar]
  76. Lu S. Li M. Cheng Z. Liang Y. Huang J. Huang J. Wang K. Yao D. Chen E. Wang P. Li Y. Huang L. HMGB1-mediated macrophage regulation of NF-κB activation and MMP3 upregulation in nucleus pulposus cells: A critical mechanism in the vicious cycle of intervertebral disc degeneration. Cell. Signal. 2025 127 111628 10.1016/j.cellsig.2025.111628 39880103
    [Google Scholar]
  77. Idoudi S. Bedhiafi T. Pedersen S. Elahtem M. Alremawi I. Akhtar S. Dermime S. Merhi M. Uddin S. Role of HMGB1 and its associated signaling pathways in human malignancies. Cell. Signal. 2023 112 110904 10.1016/j.cellsig.2023.110904 37757902
    [Google Scholar]
  78. Seo J.H. Guo S. Lok J. Navaratna D. Whalen M.J. Kim K.W. Lo E.H. Neurovascular matrix metalloproteinases and the blood-brain barrier. Curr. Pharm. Des. 2012 18 25 3645 3648 10.2174/138161212802002742 22574977
    [Google Scholar]
  79. Breteler M.M.B. Claus J.J. Grobbee D.E. Hofman A. Cardiovascular disease and distribution of cognitive function in elderly people: The Rotterdam study. BMJ 1994 308 6944 1604 1608 10.1136/bmj.308.6944.1604 8025427
    [Google Scholar]
  80. Ikram M.A. van Oijen M. de Jong F.J. Kors J.A. Koudstaal P.J. Hofman A. Witteman J.C.M. Breteler M.M.B. Unrecognized myocardial infarction in relation to risk of dementia and cerebral small vessel disease. Stroke 2008 39 5 1421 1426 10.1161/STROKEAHA.107.501106 18323497
    [Google Scholar]
  81. Sundbøll J. Horváth-Puhó E. Adelborg K. Schmidt M. Pedersen L. Bøtker H.E. Henderson V.W. Toft Sørensen H. Higher risk of vascular dementia in myocardial infarction survivors. Circulation 2018 137 6 567 577 10.1161/CIRCULATIONAHA.117.029127 29025764
    [Google Scholar]
  82. Aronson M.K. Ooi W.L. Morgenstern H. Hafner A. Masur D. Crystal H. Frishman W.H. Fisher D. Katzman R. Women, myocardial infarction, and dementia in the very old. Neurology 1990 40 7 1102 1106 10.1212/WNL.40.7.1102 2356012
    [Google Scholar]
  83. Müllges W. Berg D. Schmidtke A. Weinacker B. Toyka K.V. Early natural course of transient encephalopathy after coronary artery bypass grafting. Crit. Care Med. 2000 28 6 1808 1811 10.1097/00003246‑200006000‑00020 10890624
    [Google Scholar]
  84. Keith J.R. Puente A.E. Malcolmson K.L. Tartt S. Coleman A.E. Marks H.F. Assessing postoperative cognitive change after cardiopulmonary bypass surgery. Neuropsychology 2002 16 3 411 421 10.1037/0894‑4105.16.3.411 12146688
    [Google Scholar]
  85. Selnes O.A. Royall R.M. Grega M.A. Borowicz L.M. Quaskey S. McKhann G.M. Cognitive changes 5 years after coronary artery bypass grafting: Is there evidence of late decline? Arch. Neurol. 2001 58 4 598 604 10.1001/archneur.58.4.598 11295990
    [Google Scholar]
  86. Symes E. Maruff P. Ajani A. Currie J. Issues associated with the identification of cognitive change following coronary artery bypass grafting. Aust. N. Z. J. Psychiatry 2000 34 5 770 784 10.1080/j.1440‑1614.2000.00808.x 11037363
    [Google Scholar]
  87. Hong X. Bu L. Wang Y. Xu J. Wu J. Huang Y. Liu J. Suo H. Yang L. Shi Y. Lou Y. Sun Z. Zhu G. Behnisch T. Yu M. Jia J. Hai W. Meng H. Liang S. Huang F. Zou Y. Ge J. Increases in the risk of cognitive impairment and alterations of cerebral β-amyloid metabolism in mouse model of heart failure. PLoS One 2013 8 5 e63829 10.1371/journal.pone.0063829 23737953
    [Google Scholar]
  88. Lu Z. Yang T. Wang L. Qiu Q. Zhao Y. Wu A. Li T. Cheng W. Wang B. Li Y. Yang J. Zhao M. Comparison of different protocols of Morris water maze in cognitive impairment with heart failure. Brain Behav. 2020 10 2 e01519 10.1002/brb3.1519 31944619
    [Google Scholar]
  89. Meissner A. Visanji N.P. Momen M.A. Feng R. Francis B.M. Bolz S.S. Hazrati L.N. Tumor necrosis factor‐α underlies loss of cortical dendritic spine density in a mouse model of congestive heart failure. J. Am. Heart Assoc. 2015 4 5 e001920 10.1161/JAHA.115.001920 25948533
    [Google Scholar]
  90. Wang Y. Zhou L. Jiang H. Yu L. Editorial: Autonomic nervous system and cardiovascular diseases: From brain to heart. Front. Physiol. 2022 13 884832 10.3389/fphys.2022.884832 35574478
    [Google Scholar]
  91. Jiang H. Lu Z. Yu Y. Zhao D. Yang B. Huang C. Relationship between sympathetic nerve sprouting and repolarization dispersion at peri-infarct zone after myocardial infarction. Auton. Neurosci. 2007 134 1-2 18 25 10.1016/j.autneu.2007.01.014 17350347
    [Google Scholar]
  92. Lee C.C. Chen S. Lee T.M. 17β‐Oestradiol facilitates M2 macrophage skewing and ameliorates arrhythmias in ovariectomized female infarcted rats. J. Cell. Mol. Med. 2022 26 12 3396 3409 10.1111/jcmm.17344 35514058
    [Google Scholar]
  93. Lorentz C.U. Parrish D.C. Alston E.N. Pellegrino M.J. Woodward W.R. Hempstead B.L. Habecker B.A. Sympathetic denervation of peri-infarct myocardium requires the p75 neurotrophin receptor. Exp. Neurol. 2013 249 111 119 10.1016/j.expneurol.2013.08.015 24013014
    [Google Scholar]
  94. Tu G. Zou L. Liu S. Wu B. Lv Q. Wang S. Xue Y. Zhang C. Yi Z. Zhang X. Li G. Liang S. Long noncoding NONRATT021972 siRNA normalized abnormal sympathetic activity mediated by the upregulation of P2X7 receptor in superior cervical ganglia after myocardial ischemia. Purinergic Signal. 2016 12 3 521 535 10.1007/s11302‑016‑9518‑3 27215605
    [Google Scholar]
  95. Kimura K. Ieda M. Fukuda K. Development, maturation, and transdifferentiation of cardiac sympathetic nerves. Circ. Res. 2012 110 2 325 336 10.1161/CIRCRESAHA.111.257253 22267838
    [Google Scholar]
  96. Kimura K. Kanazawa H. Ieda M. Kawaguchi-Manabe H. Miyake Y. Yagi T. Arai T. Sano M. Fukuda K. Norepinephrine-induced nerve growth factor depletion causes cardiac sympathetic denervation in severe heart failure. Auton. Neurosci. 2010 156 1-2 27 35 10.1016/j.autneu.2010.02.005 20335077
    [Google Scholar]
  97. Francis N. Farinas I. Brennan C. Rivas-Plata K. Backus C. Reichardt L. Landis S. NT-3, like NGF, is required for survival of sympathetic neurons, but not their precursors. Dev. Biol. 1999 210 2 411 427 10.1006/dbio.1999.9269 10357900
    [Google Scholar]
  98. Hasan W. Autonomic cardiac innervation. Organogenesis 2013 9 3 176 193 10.4161/org.24892 23872607
    [Google Scholar]
  99. Frade J.M. Barde Y.A. Nerve growth factor: Two receptors, multiple functions. BioEssays 1998 20 2 137 145 10.1002/(SICI)1521‑1878(199802)20:2137::AID‑BIES6>3.0.CO;2‑Q 9631659
    [Google Scholar]
  100. Rajendran P.S. Nakamura K. Ajijola O.A. Vaseghi M. Armour J.A. Ardell J.L. Shivkumar K. Myocardial infarction induces structural and functional remodelling of the intrinsic cardiac nervous system. J. Physiol. 2016 594 2 321 341 10.1113/JP271165 26572244
    [Google Scholar]
  101. Narvaez Linares N.F. Munelith-Souksanh K. Tanguay A.F.N. Plamondon H. The impact of myocardial infarction on basal and stress-induced heart rate variability and cortisol secretion in women: A pilot study. Compr. Psychoneuroendocrinol. 2022 9 100113 10.1016/j.cpnec.2022.100113 35755922
    [Google Scholar]
  102. Schunke K.J. Rodriguez J. Dyavanapalli J. Schloen J. Wang X. Escobar J. Kowalik G. Cheung E.C. Ribeiro C. Russo R. Alber B.R. Dergacheva O. Chen S.W. Murillo-Berlioz A.E. Lee K.B. Trachiotis G. Entcheva E. Brantner C.A. Mendelowitz D. Kay M.W. Outcomes of hypothalamic oxytocin neuron-driven cardioprotection after acute myocardial infarction. Basic Res. Cardiol. 2023 118 1 43 10.1007/s00395‑023‑01013‑1 37801130
    [Google Scholar]
  103. Vanherle L. Lidington D. Uhl F.E. Steiner S. Vassallo S. Skoug C. Duarte J.M.N. Ramu S. Uller L. Desjardins J.F. Connelly K.A. Bolz S.S. Meissner A. Restoring myocardial infarction-induced long-term memory impairment by targeting the cystic fibrosis transmembrane regulator. EBioMedicine 2022 86 104384 10.1016/j.ebiom.2022.104384 36462404
    [Google Scholar]
  104. Khan H. Gamble D.T. Rudd A. Mezincescu A.M. Abbas H. Noman A. Stewart A. Horgan G. Krishnadas R. Williams C. Waiter G.D. Dawson D.K. Structural and functional brain changes in acute takotsubo syndrome. JACC Heart Fail. 2023 11 3 307 317 10.1016/j.jchf.2022.11.001 36752489
    [Google Scholar]
  105. Chang M. Wang H. Lei Y. Yang H. Xu J. Tang S. Proteomic study of left ventricle and cortex in rats after myocardial infarction. Sci. Rep. 2024 14 1 6866 10.1038/s41598‑024‑56816‑6 38514755
    [Google Scholar]
  106. Evonuk K.S. Prabhu S.D. Young M.E. DeSilva T.M. Myocardial ischemia/reperfusion impairs neurogenesis and hippocampal-dependent learning and memory. Brain Behav. Immun. 2017 61 266 273 10.1016/j.bbi.2016.09.001 27600185
    [Google Scholar]
  107. Bennardo M. Alibhai F. Tsimakouridze E. Chinnappareddy N. Podobed P. Reitz C. Pyle W.G. Simpson J. Martino T.A. Day-night dependence of gene expression and inflammatory responses in the remodeling murine heart post-myocardial infarction. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2016 311 6 R1243 R1254 10.1152/ajpregu.00200.2016 27733386
    [Google Scholar]
  108. Huynh P. Hoffmann J.D. Gerhardt T. Kiss M.G. Zuraikat F.M. Cohen O. Wolfram C. Yates A.G. Leunig A. Heiser M. Gaebel L. Gianeselli M. Goswami S. Khamhoung A. Downey J. Yoon S. Chen Z. Roudko V. Dawson T. Ferreira da Silva J. Ameral N.J. Morgenroth-Rebin J. D’Souza D. Koekkoek L.L. Jacob W. Munitz J. Lee D. Fullard J.F. van Leent M.M.T. Roussos P. Kim-Schulze S. Shah N. Kleinstiver B.P. Swirski F.K. Leistner D. St-Onge M.P. McAlpine C.S. Myocardial infarction augments sleep to limit cardiac inflammation and damage. Nature 2024 635 8037 168 177 10.1038/s41586‑024‑08100‑w 39478215
    [Google Scholar]
  109. Kaplan A. Yabluchanskiy A. Ghali R. Altara R. Booz G.W. Zouein F.A. Cerebral blood flow alteration following acute myocardial infarction in mice. Biosci. Rep. 2018 38 5 BSR20180382 10.1042/BSR20180382 30061176
    [Google Scholar]
  110. Lidington D. Fares J.C. Uhl F.E. Dinh D.D. Kroetsch J.T. Sauvé M. Malik F.A. Matthes F. Vanherle L. Adel A. Momen A. Zhang H. Aschar-Sobbi R. Foltz W.D. Wan H. Sumiyoshi M. Macdonald R.L. Husain M. Backx P.H. Heximer S.P. Meissner A. Bolz S.S. CFTR therapeutics normalize cerebral perfusion deficits in mouse models of heart failure and subarachnoid hemorrhage. JACC Basic Transl. Sci. 2019 4 8 940 958 10.1016/j.jacbts.2019.07.004 31909302
    [Google Scholar]
  111. Sabayan B. Jansen S. Oleksik A.M. van Osch M.J.P. van Buchem M.A. van Vliet P. de Craen A.J.M. Westendorp R.G.J. Cerebrovascular hemodynamics in Alzheimer’s disease and vascular dementia: A meta-analysis of transcranial Doppler studies. Ageing Res. Rev. 2012 11 2 271 277 10.1016/j.arr.2011.12.009 22226802
    [Google Scholar]
  112. Zhang H. Wang Y. Lyu D. Li Y. Li W. Wang Q. Li Y. Qin Q. Wang X. Gong M. Jiao H. Liu W. Jia J. Cerebral blood flow in mild cognitive impairment and Alzheimer’s disease: A systematic review and meta-analysis. Ageing Res. Rev. 2021 71 101450 10.1016/j.arr.2021.101450 34419673
    [Google Scholar]
  113. Horstmann A. Frisch S. Jentzsch R.T. Müller K. Villringer A. Schroeter M.L. Resuscitating the heart but losing the brain. Neurology 2010 74 4 306 312 10.1212/WNL.0b013e3181cbcd6f 20101036
    [Google Scholar]
  114. Muller M. van der Graaf Y. Algra A. Hendrikse J. Mali W.P. Geerlings M.I. Carotid atherosclerosis and progression of brain atrophy: The SMART‐MR Study. Ann. Neurol. 2011 70 2 237 244 10.1002/ana.22392 21674583
    [Google Scholar]
  115. Cipolla M.J. Integrated systems physiology: From molecule to function. The cerebral circulation. Morgan Claypool Life Sciences 2009
    [Google Scholar]
  116. Amanzio M. Palermo S. Stanziano M. D’Agata F. Galati A. Gentile S. Castellano G. Bartoli M. Cipriani G.E. Rubino E. Fonio P. Rainero I. Investigating neuroimaging correlates of early frailty in patients with behavioral variant frontotemporal dementia: A MRI and FDG-PET Study. Front. Aging Neurosci. 2021 13 637796 10.3389/fnagi.2021.637796 33935684
    [Google Scholar]
  117. Gorelick P.B. Scuteri A. Black S.E. DeCarli C. Greenberg S.M. Iadecola C. Launer L.J. Laurent S. Lopez O.L. Nyenhuis D. Petersen R.C. Schneider J.A. Tzourio C. Arnett D.K. Bennett D.A. Chui H.C. Higashida R.T. Lindquist R. Nilsson P.M. Roman G.C. Sellke F.W. Seshadri S. Vascular contributions to cognitive impairment and dementia: A statement for healthcare professionals from the american heart association/american stroke association. Stroke 2011 42 9 2672 2713 10.1161/STR.0b013e3182299496 21778438
    [Google Scholar]
  118. Roman D.D. Kubo S.H. Ormaza S. Francis G.S. Bank A.J. Shumway S.J. Memory improvement following cardiac transplantation. J. Clin. Exp. Neuropsychol. 1997 19 5 692 697 10.1080/01688639708403754 9408799
    [Google Scholar]
  119. Pun P.B.L. Lu J. Moochhala S. Involvement of ROS in BBB dysfunction. Free Radic. Res. 2009 43 4 348 364 10.1080/10715760902751902 19241241
    [Google Scholar]
  120. Cramer T. Gill R. Thirouin Z.S. Vaas M. Sampath S. Martineau F. Noya S.B. Panzanelli P. Sudharshan T.J.J. Colameo D. Chang P.K.Y. Wu P.Y. Shi R. Barker P.A. Brown S.A. Paolicelli R.C. Klohs J. McKinney R.A. Tyagarajan S.K. Cross-talk between GABAergic postsynapse and microglia regulate synapse loss after brain ischemia. Sci. Adv. 2022 8 9 eabj0112 10.1126/sciadv.abj0112 35245123
    [Google Scholar]
  121. van der Velpen I.F. Yancy C.W. Sorond F.A. Sabayan B. Impaired cardiac function and cognitive brain aging. Can. J. Cardiol. 2017 33 12 1587 1596 10.1016/j.cjca.2017.07.008 28966021
    [Google Scholar]
  122. Thorp E.B. Filipp M. Dima M. Tan C. Feinstein M. Popko B. DeBerge M. CCR2+ monocytes promote white matter injury and cognitive dysfunction after myocardial infarction. Brain Behav. Immun. 2024 119 818 835 10.1016/j.bbi.2024.05.004 38735403
    [Google Scholar]
  123. Heppner F.L. Ransohoff R.M. Becher B. Immune attack: The role of inflammation in Alzheimer disease. Nat. Rev. Neurosci. 2015 16 6 358 372 10.1038/nrn3880 25991443
    [Google Scholar]
  124. Dworak M. Stebbing M. Kompa A.R. Rana I. Krum H. Badoer E. Attenuation of microglial and neuronal activation in the brain by ICV minocycline following myocardial infarction. Auton. Neurosci. 2014 185 43 50 10.1016/j.autneu.2014.03.007 24794248
    [Google Scholar]
  125. Rana I. Stebbing M. Kompa A. Kelly D.J. Krum H. Badoer E. Microglia activation in the hypothalamic PVN following myocardial infarction. Brain Res. 2010 1326 96 104 10.1016/j.brainres.2010.02.028 20156424
    [Google Scholar]
  126. Dworak M. Stebbing M. Kompa A.R. Rana I. Krum H. Badoer E. Sustained activation of microglia in the hypothalamic PVN following myocardial infarction. Auton. Neurosci. 2012 169 2 70 76 10.1016/j.autneu.2012.04.004 22591793
    [Google Scholar]
  127. Kang Y.M. Wang Y. Yang L.M. Elks C. Cardinale J. Yu X.J. Zhao X.F. Zhang J. Zhang L.H. Yang Z.M. Francis J. TNF-α in hypothalamic paraventricular nucleus contributes to sympathoexcitation in heart failure by modulating AT1 receptor and neurotransmitters. Tohoku J. Exp. Med. 2010 222 4 251 263 10.1620/tjem.222.251 21135513
    [Google Scholar]
  128. Thackeray J.T. Hupe H.C. Wang Y. Bankstahl J.P. Berding G. Ross T.L. Bauersachs J. Wollert K.C. Bengel F.M. Myocardial inflammation predicts remodeling and neuroinflammation after myocardial infarction. J. Am. Coll. Cardiol. 2018 71 3 263 275 10.1016/j.jacc.2017.11.024 29348018
    [Google Scholar]
  129. Ge Y. van Roon L. van Gils J.M. Geestman T. van Munsteren C.J. Smits A.M. Goumans M.J.T.H. DeRuiter M.C. Jongbloed M.R.M. Acute myocardial infarction induces remodeling of the murine superior cervical ganglia and the carotid body. Front. Cardiovasc. Med. 2022 9 758265 10.3389/fcvm.2022.758265 36277772
    [Google Scholar]
  130. Apaijai N. Moisescu D.M. Palee S. McSweeney C.M. Saiyasit N. Maneechote C. Boonnag C. Chattipakorn N. Chattipakorn S.C. Pretreatment With PCSK9 inhibitor protects the brain against cardiac ischemia/reperfusion injury through a reduction of neuronal inflammation and amyloid beta aggregation. J. Am. Heart Assoc. 2019 8 2 e010838 10.1161/JAHA.118.010838 30636486
    [Google Scholar]
  131. Sun Y. Wang Z. Hou J. Shi J. Tang Z. Wang C. Zhao H. Shuangxinfang prevents s100a9-induced macrophage/microglial inflammation to improve cardiac function and depression-like behavior in rats after acute myocardial infarction. Front. Pharmacol. 2022 13 832590 10.3389/fphar.2022.832590 35814253
    [Google Scholar]
  132. Zou J.Y. Crews F.T. TNFα potentiates glutamate neurotoxicity by inhibiting glutamate uptake in organotypic brain slice cultures: Neuroprotection by NFκB inhibition. Brain Res. 2005 1034 1-2 11 24 10.1016/j.brainres.2004.11.014 15713255
    [Google Scholar]
  133. Toyama K. Koibuchi N. Uekawa K. Hasegawa Y. Kataoka K. Katayama T. Sueta D. Ma M.J. Nakagawa T. Yasuda O. Tomimoto H. Ichijo H. Ogawa H. Kim-Mitsuyama S. Apoptosis signal-regulating kinase 1 is a novel target molecule for cognitive impairment induced by chronic cerebral hypoperfusion. Arterioscler. Thromb. Vasc. Biol. 2014 34 3 616 625 10.1161/ATVBAHA.113.302440 24371084
    [Google Scholar]
  134. Shaftel S.S. Griffin W.S.T. O’Banion M.K. The role of interleukin-1 in neuroinflammation and Alzheimer disease: An evolving perspective. J. Neuroinflammation 2008 5 1 7 10.1186/1742‑2094‑5‑7 18302763
    [Google Scholar]
  135. Wright C.B. Sacco R.L. Rundek T.R. Delman J.B. Rabbani L.E. Elkind M.S.V. Interleukin-6 is associated with cognitive function: The Northern Manhattan Study. J. Stroke Cerebrovasc. Dis. 2006 15 1 34 38 10.1016/j.jstrokecerebrovasdis.2005.08.009 16501663
    [Google Scholar]
  136. Yu Y. Weiss R.M. Wei S.G. Brain Interleukin-17A contributes to neuroinflammation and cardiac dysfunction in rats with myocardial infarction. Front. Neurosci. 2022 16 1032434 10.3389/fnins.2022.1032434 36312009
    [Google Scholar]
  137. Zhang Q. Li Y. Zhang J. Cui Y. Sun S. Chen W. Shi L. Zhang Y. Hou Z. IL-17A is a key regulator of neuroinflammation and neurodevelopment in cognitive impairment induced by sevoflurane. Free Radic. Biol. Med. 2025 227 12 26 10.1016/j.freeradbiomed.2024.11.039 39581388
    [Google Scholar]
  138. Pawelec P. Ziemka-Nalecz M. Sypecka J. Zalewska T. The Impact of the CX3CL1/CX3CR1 Axis in neurological disorders. Cells 2020 9 10 2277 10.3390/cells9102277 33065974
    [Google Scholar]
  139. Liu Y. Wu X.M. Luo Q.Q. Huang S. Yang Q.W.Q. Wang F.X. Ke Y. Qian Z.M. CX3CL1/CX3CR1-mediated microglia activation plays a detrimental role in ischemic mice brain via p38MAPK/PKC pathway. J. Cereb. Blood Flow Metab. 2015 35 10 1623 1631 10.1038/jcbfm.2015.97 25966946
    [Google Scholar]
  140. Yang W.H. Liu S.C. Tsai C.H. Fong Y.C. Wang S.J. Chang Y.S. Tang C.H. Leptin induces IL-6 expression through OBRl receptor signaling pathway in human synovial fibroblasts. PLoS One 2013 8 9 e75551 10.1371/journal.pone.0075551 24086566
    [Google Scholar]
  141. Meisel S.R. Ellis M. Pariente C. Pauzner H. Liebowitz M. David D. Shimon I. Serum leptin levels increase following acute myocardial infarction. Cardiology 2001 95 4 206 211 10.1159/000047373 11585996
    [Google Scholar]
  142. Demarchi A. Mazzucchelli I. Somaschini A. Cornara S. Dusi V. Mirizzi A.M. Ruffinazzi M. Crimi G. Ferlini M. Gnecchi M. Visconti L.O. De Servi S. De Ferrari G.M. Leptin affects the inflammatory response after STEMI. Nutr. Metab. Cardiovasc. Dis. 2020 30 6 922 924 10.1016/j.numecd.2020.02.004 32249141
    [Google Scholar]
  143. Du Y. Song Y. Zhang X. Luo Y. Zou W. Zhang J. Fu J. Leptin receptor deficiency protects mice against chronic cerebral hypoperfusion-induced neuroinflammation and white matter lesions. Mediators Inflamm. 2020 2020 1 11 10.1155/2020/7974537 33380900
    [Google Scholar]
  144. de Freitas R.C.C. Hirata R.D.C. Hirata M.H. Aikawa E. Circulating extracellular vesicles as biomarkers and drug delivery vehicles in cardiovascular diseases. Biomolecules 2021 11 3 388 10.3390/biom11030388 33808038
    [Google Scholar]
  145. Liu Y. He Z. Zhang Y. Dong Z. Bi Y. Kou J. Zhou J. Shi J. Dissimilarity of increased phosphatidylserine-positive microparticles and associated coagulation activation in acute coronary syndromes. Coron. Artery Dis. 2016 27 5 365 375 10.1097/MCA.0000000000000368 27058313
    [Google Scholar]
  146. Cui Y. Zheng L. Jiang M. Jia R. Zhang X. Quan Q. Du G. Shen D. Zhao X. Sun W. Xu H. Huang L. Circulating microparticles in patients with coronary heart disease and its correlation with interleukin-6 and C-reactive protein. Mol. Biol. Rep. 2013 40 11 6437 6442 10.1007/s11033‑013‑2758‑1 24078095
    [Google Scholar]
  147. Rodriguez J.A. Orbe J. Saenz-Pipaon G. Abizanda G. Gebara N. Radulescu F. Azcarate P.M. Alonso-Perez L. Merino D. Prosper F. Paramo J.A. Roncal C. Selective increase of cardiomyocyte derived extracellular vesicles after experimental myocardial infarction and functional effects on the endothelium. Thromb. Res. 2018 170 1 9 10.1016/j.thromres.2018.07.030 30081387
    [Google Scholar]
  148. Shi M. Liu C. Cook T.J. Bullock K.M. Zhao Y. Ginghina C. Li Y. Aro P. Dator R. He C. Hipp M.J. Zabetian C.P. Peskind E.R. Hu S.C. Quinn J.F. Galasko D.R. Banks W.A. Zhang J. Plasma exosomal α-synuclein is likely CNS-derived and increased in Parkinson’s disease. Acta Neuropathol. 2014 128 5 639 650 10.1007/s00401‑014‑1314‑y 24997849
    [Google Scholar]
  149. García-Romero N. Carrión-Navarro J. Esteban-Rubio S. Lázaro-Ibáñez E. Peris-Celda M. Alonso M.M. Guzmán-De-Villoria J. Fernández-Carballal C. de Mendivil A.O. García-Duque S. Escobedo-Lucea C. Prat-Acín R. Belda-Iniesta C. Ayuso-Sacido A. DNA sequences within glioma-derived extracellular vesicles can cross the intact blood-brain barrier and be detected in peripheral blood of patients. Oncotarget 2017 8 1 1416 1428 10.18632/oncotarget.13635 27902458
    [Google Scholar]
  150. Li J.J. Wang B. Kodali M.C. Chen C. Kim E. Patters B.J. Lan L. Kumar S. Wang X. Yue J. Liao F.F. In vivo evidence for the contribution of peripheral circulating inflammatory exosomes to neuroinflammation. J. Neuroinflammation 2018 15 1 8 10.1186/s12974‑017‑1038‑8 29310666
    [Google Scholar]
  151. Huang X. Hussain B. Chang J. Peripheral inflammation and blood-brain barrier disruption: Effects and mechanisms. CNS Neurosci. Ther. 2021 27 1 36 47 10.1111/cns.13569 33381913
    [Google Scholar]
  152. Li L. Li F. Bai X. Jia H. Wang C. Li P. Zhang Q. Guan S. Peng R. Zhang S. Dong J. Zhang J. Xu X. Circulating extracellular vesicles from patients with traumatic brain injury induce cerebrovascular endothelial dysfunction. Pharmacol. Res. 2023 192 106791 10.1016/j.phrs.2023.106791 37156450
    [Google Scholar]
  153. Zhou S. Jin J. Wang J. Zhang Z. Freedman J.H. Zheng Y. Cai L. MIRNAS in cardiovascular diseases: Potential biomarkers, therapeutic targets and challenges. Acta Pharmacol. Sin. 2018 39 7 1073 1084 10.1038/aps.2018.30 29877320
    [Google Scholar]
  154. Tsui N.B.Y. Ng E.K.O. Lo Y.M.D. Stability of endogenous and added RNA in blood specimens, serum, and plasma. Clin. Chem. 2002 48 10 1647 1653 10.1093/clinchem/48.10.1647 12324479
    [Google Scholar]
  155. Zampetaki A. Willeit P. Drozdov I. Kiechl S. Mayr M. Profiling of circulating microRNAs: From single biomarkers to re-wired networks. Cardiovasc. Res. 2012 93 4 555 562 10.1093/cvr/cvr266 22028337
    [Google Scholar]
  156. Kosaka N. Iguchi H. Yoshioka Y. Takeshita F. Matsuki Y. Ochiya T. Secretory mechanisms and intercellular transfer of microRNAs in living cells. J. Biol. Chem. 2010 285 23 17442 17452 10.1074/jbc.M110.107821 20353945
    [Google Scholar]
  157. Gidlöf O. Smith J.G. Miyazu K. Gilje P. Spencer A. Blomquist S. Erlinge D. Circulating cardio-enriched microRNAs are associated with long-term prognosis following myocardial infarction. BMC Cardiovasc. Disord. 2013 13 1 12 10.1186/1471‑2261‑13‑12 23448306
    [Google Scholar]
  158. Liu X. Fan Z. Zhao T. Cao W. Zhang L. Li H. Xie Q. Tian Y. Wang B. Plasma miR-1, miR-208, miR-499 as potential predictive biomarkers for acute myocardial infarction: An independent study of Han population. Exp. Gerontol. 2015 72 230 238 10.1016/j.exger.2015.10.011 26526403
    [Google Scholar]
  159. Cheng M. Yang J. Zhao X. Zhang E. Zeng Q. Yu Y. Yang L. Wu B. Yi G. Mao X. Huang K. Dong N. Xie M. Limdi N.A. Prabhu S.D. Zhang J. Qin G. Circulating myocardial microRNAs from infarcted hearts are carried in exosomes and mobilise bone marrow progenitor cells. Nat. Commun. 2019 10 1 959 10.1038/s41467‑019‑08895‑7 30814518
    [Google Scholar]
  160. Wang G.K. Zhu J.Q. Zhang J.T. Li Q. Li Y. He J. Qin Y.W. Jing Q. Circulating microRNA: A novel potential biomarker for early diagnosis of acute myocardial infarction in humans. Eur. Heart J. 2010 31 6 659 666 10.1093/eurheartj/ehq013 20159880
    [Google Scholar]
  161. Chang C.Y. Lui T.N. Lin J.W. Lin Y.L. Hsing C.H. Wang J.J. Chen R.M. Roles of microRNA-1 in hypoxia-induced apoptotic insults to neuronal cells. Arch. Toxicol. 2016 90 1 191 202 10.1007/s00204‑014‑1364‑x 25238743
    [Google Scholar]
  162. Selvamani A. Sathyan P. Miranda R.C. Sohrabji F. An antagomir to microRNA Let7f promotes neuroprotection in an ischemic stroke model. PLoS One 2012 7 2 e32662 10.1371/journal.pone.0032662 22393433
    [Google Scholar]
  163. Varendi K. Kumar A. Härma M.A. Andressoo J.O. MIR-1, miR-10b, miR-155, and miR-191 are novel regulators of BDNF. Cell. Mol. Life Sci. 2014 71 22 4443 4456 10.1007/s00018‑014‑1628‑x 24804980
    [Google Scholar]
  164. Ma J.C. Duan M.J. Sun L.L. Yan M.L. Liu T. Wang Q. Liu C.D. Wang X. Kang X.H. Pei S.C. Zong D.K. Chen X. Wang N. Ai J. Cardiac over-expression of microRNA-1 induces impairment of cognition in mice. Neuroscience 2015 299 66 78 10.1016/j.neuroscience.2015.04.061 25943483
    [Google Scholar]
  165. Ma J.C. Duan M.J. Li K.X. Biddyut D. Zhang S. Yan M.L. Yang L. Jin Z. Zhao H.M. Huang S.Y. Sun Q. Su D. Xu Y. Pan Y.H. Ai J. Knockdown of microrna-1 in the hippocampus ameliorates myocardial infarction induced impairment of long-term potentiation. Cell. Physiol. Biochem. 2018 50 4 1601 1616 10.1159/000494657 30359966
    [Google Scholar]
  166. Nouri Z. Barfar A. Perseh S. Motasadizadeh H. Maghsoudian S. Fatahi Y. Nouri K. Yektakasmaei M.P. Dinarvand R. Atyabi F. Exosomes as therapeutic and drug delivery vehicle for neurodegenerative diseases. J. Nanobiotechnology 2024 22 1 463 10.1186/s12951‑024‑02681‑4 39095888
    [Google Scholar]
  167. Anderson G. Gut microbiome and circadian interactions with platelets across human diseases, including alzheimer’s disease, amyotrophic lateral sclerosis, and cancer. Curr. Top. Med. Chem. 2023 23 28 2699 2719 10.2174/0115680266253465230920114223 37807406
    [Google Scholar]
  168. Meyer R.K. Duca F.A. RISING STARS: Endocrine regulation of metabolic homeostasis via the intestine and gut microbiome. J. Endocrinol. 2023 258 2 e230019 10.1530/JOE‑23‑0019 37171833
    [Google Scholar]
  169. Chen H.C. Liu Y.W. Chang K.C. Wu Y.W. Chen Y.M. Chao Y.K. You M.Y. Lundy D.J. Lin C.J. Hsieh M.L. Cheng Y.C. Prajnamitra R.P. Lin P.J. Ruan S.C. Chen D.H.K. Shih E.S.C. Chen K.W. Chang S.S. Chang C.M.C. Puntney R. Moy A.W. Cheng Y.Y. Chien H.Y. Lee J.J. Wu D.C. Hwang M.J. Coonen J. Hacker T.A. Yen C.L.E. Rey F.E. Kamp T.J. Hsieh P.C.H. Gut butyrate-producers confer post-infarction cardiac protection. Nat. Commun. 2023 14 1 7249 10.1038/s41467‑023‑43167‑5 37945565
    [Google Scholar]
  170. Anderson G. Maes M. Role of opioidergic system in regulating depression pathophysiology. Curr. Pharm. Des. 2020 26 41 5317 5334 10.2174/1381612826666200806101744 32767926
    [Google Scholar]
  171. Pontes G.N. Cardoso E.C. Carneiro-Sampaio M.M.S. Markus R.P. Pineal melatonin and the innate immune response: The TNF‐α increase after cesarean section suppresses nocturnal melatonin production. J. Pineal Res. 2007 43 4 365 371 10.1111/j.1600‑079X.2007.00487.x 17910605
    [Google Scholar]
  172. Kim R. Kim M. Jeong S. Kim S. Moon H. Kim H. Lee M.Y. Kim J. Kim H.S. Choi M. Shin K. Song B.W. Chang W. Melatonin alleviates myocardial dysfunction through inhibition of endothelial‐to‐mesenchymal transition via the NF‐κB pathway. J. Pineal Res. 2024 76 4 e12958 10.1111/jpi.12958 38747060
    [Google Scholar]
  173. Lu L.L. Liu L.Z. Li L. Hu Y.Y. Xian X.H. Li W.B. Sodium butyrate improves cognitive dysfunction in high-fat diet/streptozotocin-induced type 2 diabetic mice by ameliorating hippocampal mitochondrial damage through regulating AMPK/PGC-1α pathway. Neuropharmacology 2024 261 110139 10.1016/j.neuropharm.2024.110139 39233201
    [Google Scholar]
  174. Sumsuzzman D.M. Choi J. Jin Y. Hong Y. Neurocognitive effects of melatonin treatment in healthy adults and individuals with Alzheimer’s disease and insomnia: A systematic review and meta-analysis of randomized controlled trials. Neurosci. Biobehav. Rev. 2021 127 459 473 10.1016/j.neubiorev.2021.04.034 33957167
    [Google Scholar]
  175. Hadaya J. Dajani A.H. Cha S. Hanna P. Challita R. Hoover D.B. Ajijola O.A. Shivkumar K. Ardell J.L. Vagal nerve stimulation reduces ventricular arrhythmias and mitigates adverse neural cardiac remodeling post-myocardial infarction. JACC Basic Transl. Sci. 2023 8 9 1100 1118 10.1016/j.jacbts.2023.03.025 37791302
    [Google Scholar]
  176. Li X. Zhu X. Li B. Xia B. Tang H. Hu J. Ying R. Loss of α7nAChR enhances endothelial‐to‐mesenchymal transition after myocardial infarction via NF-κB activation. Exp. Cell Res. 2022 419 1 113300 10.1016/j.yexcr.2022.113300 35926661
    [Google Scholar]
  177. Alzarea S. Khan A. Ronan P.J. Lutfy K. Rahman S. The α-7 nicotinic receptor positive allosteric modulator alleviates lipopolysaccharide induced depressive-like behavior by regulating microglial function, trophic factor, and chloride transporters in mice. Brain Sci. 2024 14 3 290 10.3390/brainsci14030290 38539677
    [Google Scholar]
  178. Markus R.P. Silva C.L.M. Franco D.G. Barbosa E.M. Ferreira Z.S. Is modulation of nicotinic acetylcholine receptors by melatonin relevant for therapy with cholinergic drugs? Pharmacol. Ther. 2010 126 3 251 262 10.1016/j.pharmthera.2010.02.009 20398699
    [Google Scholar]
  179. Sethi Y. Padda I. Sebastian S.A. Malhi A. Malhi G. Fulton M. Khehra N. Mahtani A. Parmar M. Johal G. Glucocorticoid receptor antagonism and cardiomyocyte regeneration following myocardial infarction: A systematic review. Curr. Probl. Cardiol. 2023 48 12 101986 10.1016/j.cpcardiol.2023.101986 37481215
    [Google Scholar]
  180. Bruns B. Daub R. Schmitz T. Hamze-Sinno M. Spaich S. Dewenter M. Schwale C. Gass P. Vogt M. Katus H. Herzog W. Friederich H.C. Frey N. Schultz J.H. Backs J. Forebrain corticosteroid receptors promote post-myocardial infarction depression and mortality. Basic Res. Cardiol. 2022 117 1 44 10.1007/s00395‑022‑00951‑6 36068417
    [Google Scholar]
  181. Anderson G. Polycystic ovary syndrome pathophysiology: Integrating systemic, cns and circadian processes. Front. Biosci. 2024 29 1 24 10.31083/j.fbl2901024 38287831
    [Google Scholar]
  182. Jin L. Geng L. Ying L. Shu L. Ye K. Yang R. Liu Y. Wang Y. Cai Y. Jiang X. Wang Q. Yan X. Liao B. Liu J. Duan F. Sweeney G. Woo C.W.H. Wang Y. Xia Z. Lian Q. Xu A. FGF21-sirtuin 3 axis confers the protective effects of exercise against diabetic cardiomyopathy by governing mitochondrial integrity. Circulation 2022 146 20 1537 1557 10.1161/CIRCULATIONAHA.122.059631 36134579
    [Google Scholar]
  183. Li J. Gong L. Zhang R. Li S. Yu H. Liu Y. Xue Y. Huang D. Xu N. Wang Y. Xu Y. Zhao Y. Li Q. Li M. Li P. Liu M. Zhang Z. Li X. Du W. Wang N. Fibroblast growth factor 21 inhibited inflammation and fibrosis after myocardial infarction via EGR1. Eur. J. Pharmacol. 2021 910 174470 10.1016/j.ejphar.2021.174470 34478691
    [Google Scholar]
  184. Liu X. Dong M. Li T. Wang J. Correlation of circulating fibroblast growth factor 21 levels with inflammatory factors and the degree of coronary artery stenosis in patients with acute myocardial infarction. Cytokine 2024 178 156591 10.1016/j.cyto.2024.156591 38554500
    [Google Scholar]
  185. Rao Z. Tang Y. Zhu J. Lu Z. Chen Z. Wang J. Bao Y. Mukondiwa A.V. Wang C. Wang X. Luo Y. Li X. Enhanced FGF21 delivery via neutrophil-membrane-coated nanoparticles improves therapeutic efficacy for myocardial ischemia-reperfusion injury. Nanomaterials (Basel) 2025 15 5 346 10.3390/nano15050346 40072149
    [Google Scholar]
  186. Hsuchou H. Pan W. Kastin A.J. The fasting polypeptide FGF21 can enter brain from blood. Peptides 2007 28 12 2382 2386 10.1016/j.peptides.2007.10.007 17996984
    [Google Scholar]
  187. Chen J. Hu J. Liu H. Xiong Y. Zou Y. Huang W. Shao M. Wu J. Yu L. Wang X. Wang X. Lin L. FGF21 Protects the Blood-Brain Barrier by Upregulating PPARγ via FGFR1/β-klotho after Traumatic Brain Injury. J. Neurotrauma 2018 35 17 2091 2103 10.1089/neu.2017.5271 29648978
    [Google Scholar]
  188. Wang D. Liu F. Zhu L. Lin P. Han F. Wang X. Tan X. Lin L. Xiong Y. FGF21 alleviates neuroinflammation following ischemic stroke by modulating the temporal and spatial dynamics of microglia/macrophages. J. Neuroinflammation 2020 17 1 257 10.1186/s12974‑020‑01921‑2 32867781
    [Google Scholar]
  189. Wang X. Zhu L. Hu J. Guo R. Ye S. Liu F. Wang D. Zhao Y. Hu A. Wang X. Guo K. Lin L. FGF21 Attenuated LPS-induced depressive-like behavior via inhibiting the inflammatory pathway. Front. Pharmacol. 2020 11 154 10.3389/fphar.2020.00154 32184729
    [Google Scholar]
  190. Fang M. Lu L. Lou J. Ou J. Yu Q. Tao X. Zhu J. Lin Z. FGF21 Alleviates hypoxic-ischemic white matter injury in neonatal mice by mediating inflammation and oxidative stress through ppar-γ signaling pathway. Mol. Neurobiol. 2025 62 4 4743 4768 10.1007/s12035‑024‑04549‑y 39485628
    [Google Scholar]
  191. Carloni S. Nasoni M.G. Casabianca A. Orlandi C. Capobianco L. Iaconisi G.N. Cerioni L. Burattini S. Benedetti S. Reiter R.J. Balduini W. Luchetti F. Melatonin reduces mito‐inflammation in ischaemic hippocampal HT22 cells and modulates the cGAS - STING cytosolic DNA sensing pathway and FGF21 release. J. Cell. Mol. Med. 2024 28 24 e70285 10.1111/jcmm.70285 39707673
    [Google Scholar]
/content/journals/cn/10.2174/011570159X394212250825051955
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Myocardial Inflammation as Key Mediator of Heart-brain Interaction After Myocardial Ischemia/Infarction: Mechanistic Exploration of Post-Myocardial Infarction Cognitive Dysfunction
Bentham Science Publishers ; https://doi.org/10.2174/011570159X394212250825051955
/content/journals/cn/10.2174/011570159X394212250825051955
/content/journals/cn/10.2174/011570159X394212250825051955
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  • Article Type:     Review Article
Keywords: blood-brain barrier ; cardiac-brain interaction ; inflammatory mediators ; Myocardial infarction ; cognitive dysfunction ; neuroinflammation

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