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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Neurol. | doi: 10.3389/fneur.2018.00965

Intracerebral hemorrhage induces cardiac dysfunction in mice without primary cardiac disease

Wei Li1, 2, Linlin Li1,  Michael Chopp2, 3,  Poornima Venkat2, Alex Zacharek,2,  Zhili Chen1, 2, Julie Landschoot-Ward2, Tao Yan1* and  Jieli Chen2*
  • 1Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin Neurological Institute, Neurology, Key Laboratory of Post-Neurotrauma Neurorepair and Regeneration in CNS, Ministry of Education and Tianjin City, Tianjin Medical University General Hospital, China
  • 2Department of Neurology, Henry Ford Hospital, United States
  • 3cDepartment of Physics, Oakland University, United States

Background: Intracerebral hemorrhage (ICH) is a life threatening stroke subtype and a worldwide health problem. In this study, we investigate brain-heart interaction after ICH in mice and test whether ICH induces cardiac dysfunction in the absence of primary cardiac disease. We also investigate underlying mechanisms such as oxidative stress and inflammatory responses in mediating cardiac dysfunction post-ICH in mice.

Methods: Male, adult (3-4m) C57BL/6J mice were subjected to sham surgery or ICH using an autologous blood injection model (n=16/group). Cardiac function was evaluated at 7 and 28 days after ICH using echocardiography (n=8/group per time point). Western blot and immunostaining analysis were employed to assess oxidative stress and inflammatory responses in the heart.

Results: Mice subjected to ICH exhibited significantly decreased cardiac contractile function measured by left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) at 7 and 28 days after ICH compared to sham-control mice (p<0.05). ICH induced cardiac dysfunction was significantly worse at 28 days than at 7 days after ICH (p<0.05). ICH in mice significantly increased cardiomyocyte apoptosis, inflammatory factor expression and inflammatory cell infiltration in heart tissue, and induced cardiac oxidative stress at 7 days post-ICH compared to sham-control mice. Compared to sham-control mice, ICH-mice also exhibited significantly increased (p<0.05) cardiomyocyte hypertrophy and cardiac fibrosis at 28 days after ICH.

Conclusions: ICH induces significant and progressive cardiac dysfunction in mice. ICH increases cardiac oxidative stress and inflammatory factor expression in heart tissue which may play key roles in ICH-induced cardiac dysfunction.

Keywords: brain-heart axis, Cardiac dysfunction, Cardiac inflammation, intracerebral hemorrhage, Oxidative Stress

Received: 24 Aug 2018; Accepted: 26 Oct 2018.

Edited by:

Midori A. Yenari, University of California, San Francisco, United States

Reviewed by:

Jong Youl Kim, Yonsei University College of Medicine, South Korea
Atsushi Mizuma, Tokai University, Japan  

Copyright: © 2018 Li, Li, Chopp, Venkat, Zacharek,, Chen, Landschoot-Ward, Yan and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
PhD. Tao Yan, Tianjin Medical University General Hospital, Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin Neurological Institute, Neurology, Key Laboratory of Post-Neurotrauma Neurorepair and Regeneration in CNS, Ministry of Education and Tianjin City, Tianjin, China, yantao78@hotmail.com
MD. Jieli Chen, Henry Ford Hospital, Department of Neurology, Detroit, Michigan, United States, jieli@neuro.hfh.edu