Ischemic stroke induces gut permeability and enhances bacterial translocation leading to sepsis in aged mice.
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.
University of Connecticut Health Center Department of Neuroscience, Farmington, CT 06030, USA.
Joshua
J
Crapser
University of Connecticut Health Center Department of Neuroscience, Farmington, CT 06030, USA.
Rodney
R
Ritzel
University of Connecticut Health Center Department of Neuroscience, Farmington, CT 06030, USA.
Rajkumar
R
Verma
University of Connecticut Health Center Department of Neuroscience, Farmington, CT 06030, USA.
Venugopal R
VR
Venna
University of Connecticut Health Center Department of Neuroscience, Farmington, CT 06030, USA.
Fudong
F
Liu
University of Connecticut Health Center Department of Neuroscience, Farmington, CT 06030, USA.
Anjali
A
Chauhan
University of Connecticut Health Center Department of Neuroscience, Farmington, CT 06030, USA.
Edward
E
Koellhoffer
University of Michigan Department of Neuroscience, Ann Arbor, MI 48109, USA.
Anita
A
Patel
University of Connecticut Department of Molecular and Cell Biology, Storrs, CT 06269, USA.
Austin
A
Ricker
University of Connecticut Department of Molecular and Cell Biology, Storrs, CT 06269, USA.
Kendra
K
Maas
University of Connecticut Department of Molecular and Cell Biology, Storrs, CT 06269, USA.
Joerg
J
Graf
University of Connecticut Health Center Department of Neuroscience, Farmington, CT 06030, USA.|University of Texas Health Science Center at Houston, McGovern Medical School, Houston, TX 77030, USA.
Louise D
LD
McCullough
D056704:Adaptive Immunity / Q000502:physiology; D000375:Aging / Q000378:metabolism*; D000818:Animals; D018988:Bacterial Translocation / Q000502:physiology*; D002545:Brain Ischemia / Q000150:complications / Q000378:metabolism*; D004195:Disease Models, Animal; D005753:Gastric Mucosa / Q000378:metabolism; D007113:Immunity, Innate / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D010539:Permeability; D018805:Sepsis / Q000378:metabolism / Q000382:microbiology*; D020521:Stroke / Q000150:complications / Q000378:metabolism*
aging; experimental stroke; infection; inflammation; middle cerebral artery occlusion