Research Paper|Volume 8, Issue 5|pp 1049—1060

Ischemic stroke induces gut permeability and enhances bacterial translocation leading to sepsis in aged mice

Joshua Crapser¹, Rodney Ritzel¹, Rajkumar Verma¹, Venugopal R. R. Venna¹, Fudong Liu¹, Anjali Chauhan¹, Edward Koellhoffer¹, Anita Patel², Austin Ricker³, Kendra Maas³, Joerg Graf³, Louise D. D. McCullough^1,⁴

¹University of Connecticut Health Center Department of Neuroscience, Farmington, CT 06030, USA
²University of Michigan Department of Neuroscience, Ann Arbor, MI 48109, USA
³University of Connecticut Department of Molecular and Cell Biology, Storrs, CT 06269, USA
⁴University of Texas Health Science Center at Houston, McGovern Medical School, Houston, TX 77030, USA

* * Equal contribution

Received: January 20, 2016Accepted: April 20, 2016Published: April 25, 2016

https://doi.org/10.18632/aging.100952

Copyright: © 2016 Crapser et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Aging is an important risk factor for post-stroke infection, which accounts for a large proportion of stroke-associated mortality. Despite this, studies evaluating post-stroke infection rates in aged animal models are limited. In addition, few studies have assessed gut microbes as a potential source of infection following stroke. Therefore we investigated the effects of age and the role of bacterial translocation from the gut in post-stroke infection in young (8-12 weeks) and aged (18-20 months) C57Bl/6 male mice following transient middle cerebral artery occlusion (MCAO) or sham surgery. Gut permeability was examined and peripheral organs were assessed for the presence of gut-derived bacteria following stroke. Furthermore, sickness parameters and components of innate and adaptive immunity were examined. We found that while stroke induced gut permeability and bacterial translocation in both young and aged mice, only young mice were able to resolve infection. Bacterial species seeding peripheral organs also differed between young (Escherichia) and aged (Enterobacter) mice. Consequently, aged mice developed a septic response marked by persistent and exacerbated hypothermia, weight loss, and immune dysfunction compared to young mice following stroke.