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Stroke Severity, and Not Cerebral Infarct Location, Increases the Risk of Infection

  • Raymond Shim
  • Shu Wen Wen
  • Brooke J. Wanrooy
  • Michelle Rank
  • Tharani Thirugnanachandran
  • Luke Ho
  • Tara Sepehrizadeh
  • Michael de Veer
  • Velandai K. Srikanth
  • Henry Ma
  • Thanh G. Phan
  • Christopher G. Sobey
  • Connie H. Y. WongEmail author
Original Article

Abstract

Infection is a leading cause of death in patients with stroke; however, the impact of cerebral infarct size or location on infectious outcome is unclear. To examine the effect of infarct size on post-stroke infection, we utilised the intraluminal middle-cerebral artery occlusion (MCAO) mouse model of ischemic stroke and adjusted the duration of arterial occlusion. At 1 day following stroke onset, the proportion of mice with infection was significantly greater in mice that had larger infarct sizes. Additionally, the presence of lung infection in these mice with severe strokes extended past 2 days, suggestive of long-term immune impairment. At the acute phase, our data demonstrated an inverse relationship between infarct volume and the number of circulating leukocytes, indicating the elevated risk of infection in more severe stroke is associated with reduced cellularity in peripheral blood, owing predominately to markedly decreased lymphocyte numbers. In addition, the stroke-induced reduction of lymphocyte-to-neutrophil ratio was also evident in the lung of all post-stroke animals. To investigate the effect of infarct location on post-stroke infection, we additionally performed a photothrombotic (PT) model of stroke and using an innovative systematic approach of analysis, we found the location of cerebral infarct does not impact on the susceptibility of post-stroke infection, confirming the greater role of infarct volume over infarct location in the susceptibility to infection. Our experimental findings were validated in a clinical setting and reinforced that stroke severity, and not infarct location, influences the risk of infection after stroke.

Keywords

Stroke Infection Infarct volume Infarct location 

Notes

Acknowledgements

The authors acknowledge the facilities and scientific and technical assistance of the National Imaging Facility, a National Collaborative Research Infrastructure Strategy (NCRIS) capability, at the Monash Biomedical Imaging, Monash University. The authors acknowledge the facilities and technical assistance of Monash Histology Platform, at the Department of Anatomy and Developmental Biology, Monash University.

Funding Information

This work is supported by the National Heart Foundation (NHF, Australia; 100,863), CSL Centenary Fellowship and the National Health and Medical Research Council (NHMRC, Australia: APP1104036). The financial supports have no role in conducting the research and/or preparation of the article.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

12975_2019_738_MOESM1_ESM.docx (83 kb)
ESM 1 (DOCX 83 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Raymond Shim
    • 1
  • Shu Wen Wen
    • 1
  • Brooke J. Wanrooy
    • 1
  • Michelle Rank
    • 2
    • 3
  • Tharani Thirugnanachandran
    • 4
  • Luke Ho
    • 1
    • 5
  • Tara Sepehrizadeh
    • 6
  • Michael de Veer
    • 6
  • Velandai K. Srikanth
    • 5
  • Henry Ma
    • 4
  • Thanh G. Phan
    • 4
  • Christopher G. Sobey
    • 7
  • Connie H. Y. Wong
    • 1
    Email author
  1. 1.Centre for Inflammatory Diseases, Department of Medicine at Monash Health, School of Clinical Sciences, Monash Medical CentreMonash UniversityClaytonAustralia
  2. 2.Department of Anatomy and Neuroscience, School of Biomedical SciencesThe University of MelbourneParkvilleAustralia
  3. 3.School of Health and Biomedical SciencesRMIT UniversityBundooraAustralia
  4. 4.Stroke and Ageing Research Group, Department of Medicine at Monash Health, School of Clinical Sciences, Monash Medical CentreMonash UniversityClaytonAustralia
  5. 5.Department of Medicine (Academic Unit), Peninsula Clinical School, Central Clinical SchoolMonash UniversityFrankstonAustralia
  6. 6.Monash Biomedical ImagingMonash UniversityClaytonAustralia
  7. 7.Department of Physiology, Anatomy and Microbiology, School of Life SciencesLa Trobe UniversityBundooraAustralia

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