PMID- 34126326 OWN - NLM STAT- MEDLINE DCOM- 20211025 LR - 20211025 IS - 1872-7484 (Electronic) IS - 1566-0702 (Linking) VI - 234 DP - 2021 Sep TI - Metoprolol attenuates intracerebral hemorrhage-induced cardiac damage by suppression of sympathetic overactivity in mice. PG - 102832 LID - S1566-0702(21)00062-X [pii] LID - 10.1016/j.autneu.2021.102832 [doi] AB - The high rates of mortality and disability resulting from intracerebral hemorrhage (ICH) are closely related to subsequent cardiac complications. The mechanisms underlying ICH-induced cardiac dysfunction are not fully understood. In this study, we investigated the role of sympathetic overactivity in mediating cardiac dysfunction post ICH in mice. Collagenase-injection ICH model was established in adult male C57BL/6J mice. Neurological function was subsequently evaluated at multiple time points after ICH and cardiac function was measured by echocardiography on 3 and 14 days after ICH. Plasma adrenaline, noradrenaline, cortisol and heart beta1 adrenergic receptor (beta1-AR) levels were assessed to evaluate sympathetic activity. Picro Sirius Red (PSR) staining was performed to evaluate cardiomyocyte hypertrophy and interstitial fibrosis. Monocyte chemotactic protein 1 (MCP-1), tumor necrosis factor-alpha (TNF-alpha), interleukin-6(IL-6), nuclear factor kappa-B(NF-kappaB), NADPH oxidase-2 (NOX2), matrix metalloprotein (MMP-9) and transforming growth factor-beta (TGF-beta) levels were assessed to evaluate inflammation, fibrosis and oxidative stress levels in heart after ICH. Macrophages and neutrophils were assessed to evaluate inflammatory cell infiltration in heart after ICH. ICH induced sympathetic excitability, as identified by increased circulating adrenaline, noradrenaline, cortisol levels and beta1-AR expression in heart tissue. Metoprolol-treated ICH mice had improved cardiac and neurological function. The suppression of sympathetic overactivity by metoprolol attenuates cardiac inflammation, fibrosis and oxidative stress after ICH. In conclusion, ICH-induced secondary sympathetic overactivity which mediated inflammatory response may play an important role in post-ICH cardiac dysfunction. CI - Copyright (c) 2021. Published by Elsevier B.V. FAU - Zhang, Liqun AU - Zhang L AD - Department of Neurology, Tianjin Medical University General Hospital, Tianjin Neurological Institute, Key Laboratory of Post-Neurotrauma, Neurorepair, and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin 300052, China. FAU - Wuri, Jimusi AU - Wuri J AD - Department of Neurology, Tianjin Medical University General Hospital, Tianjin Neurological Institute, Key Laboratory of Post-Neurotrauma, Neurorepair, and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin 300052, China. FAU - An, Lulu AU - An L AD - Department of Neurology, Tianjin Medical University General Hospital, Tianjin Neurological Institute, Key Laboratory of Post-Neurotrauma, Neurorepair, and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin 300052, China. FAU - Liu, Xiaoxuan AU - Liu X AD - Department of Neurology, Tianjin Medical University General Hospital, Tianjin Neurological Institute, Key Laboratory of Post-Neurotrauma, Neurorepair, and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin 300052, China. FAU - Wu, Ye AU - Wu Y AD - Department of Neurology, Tianjin Medical University General Hospital, Tianjin Neurological Institute, Key Laboratory of Post-Neurotrauma, Neurorepair, and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin 300052, China. FAU - Hu, Haotian AU - Hu H AD - Department of Neurology, Tianjin Medical University General Hospital, Tianjin Neurological Institute, Key Laboratory of Post-Neurotrauma, Neurorepair, and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin 300052, China. FAU - Wu, Ruixia AU - Wu R AD - Department of Neurology, Tianjin Medical University General Hospital, Tianjin Neurological Institute, Key Laboratory of Post-Neurotrauma, Neurorepair, and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin 300052, China. FAU - Su, Yue AU - Su Y AD - Department of Neurology, Tianjin Medical University General Hospital, Tianjin Neurological Institute, Key Laboratory of Post-Neurotrauma, Neurorepair, and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin 300052, China. FAU - Yuan, Quan AU - Yuan Q AD - Department of Neurology, Tianjin Medical University General Hospital, Tianjin Neurological Institute, Key Laboratory of Post-Neurotrauma, Neurorepair, and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin 300052, China. FAU - Yan, Tao AU - Yan T AD - Department of Neurology, Tianjin Medical University General Hospital, Tianjin Neurological Institute, Key Laboratory of Post-Neurotrauma, Neurorepair, and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin 300052, China. Electronic address: taoyan@tmu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210605 PL - Netherlands TA - Auton Neurosci JT - Autonomic neuroscience : basic & clinical JID - 100909359 RN - 0 (NF-kappa B) RN - GEB06NHM23 (Metoprolol) SB - IM MH - Animals MH - *Cerebral Hemorrhage/complications/drug therapy MH - Heart MH - Male MH - *Metoprolol/pharmacology MH - Mice MH - Mice, Inbred C57BL MH - NF-kappa B OTO - NOTNLM OT - Cardiac dysfunction OT - Cardiac fibrosis OT - Inflammation OT - Intracerebral hemorrhage OT - Sympathetic overactivity EDAT- 2021/06/15 06:00 MHDA- 2021/10/26 06:00 CRDT- 2021/06/14 20:19 PHST- 2021/04/02 00:00 [received] PHST- 2021/05/08 00:00 [revised] PHST- 2021/06/03 00:00 [accepted] PHST- 2021/06/15 06:00 [pubmed] PHST- 2021/10/26 06:00 [medline] PHST- 2021/06/14 20:19 [entrez] AID - S1566-0702(21)00062-X [pii] AID - 10.1016/j.autneu.2021.102832 [doi] PST - ppublish SO - Auton Neurosci. 2021 Sep;234:102832. doi: 10.1016/j.autneu.2021.102832. Epub 2021 Jun 5.