SAGE Journals
Browse

Metabolic endotoxemia promotes neuroinflammation after focal cerebral ischemia

Posted on 2020-01-08 - 13:09

Lipopolysaccharide (LPS) is a major component of the outer membrane of Gram-negative bacteria and a potent inflammatory stimulus for the innate immune response via toll-like receptor (TLR) 4 activation. Type 2 diabetes is associated with changes in gut microbiota and impaired intestinal barrier functions, leading to translocation of microbiota-derived LPS into the circulatory system, a condition referred to as metabolic endotoxemia. We investigated the effects of metabolic endotoxemia after experimental stroke with transient middle cerebral artery occlusion (MCAO) in a murine model of type 2 diabetes (db/db) and phenotypically normal littermates (db/+). Compared to db/+ mice, db/db mice exhibited an altered gut microbial composition, increased intestinal permeability, and higher plasma LPS levels. In addition, db/db mice presented increased infarct volumes and higher expression levels of LPS, TLR4, and inflammatory cytokines in the ischemic brain, as well as more severe neurological impairments and reduced survival rates after MCAO. Oral administration of a non-absorbable antibiotic modulated the gut microbiota and improved metabolic endotoxemia and stroke outcomes in db/db mice; these effects were associated with reduction of LPS levels and neuroinflammation in the ischemic brain. These data suggest that targeting metabolic endotoxemia may be a novel potential therapeutic strategy to improve stroke outcomes.

CITE THIS COLLECTION

DataCite
3 Biotech
3D Printing in Medicine
3D Research
3D-Printed Materials and Systems
4OR
AAPG Bulletin
AAPS Open
AAPS PharmSciTech
Abhandlungen aus dem Mathematischen Seminar der Universität Hamburg
ABI Technik (German)
Academic Medicine
Academic Pediatrics
Academic Psychiatry
Academic Questions
Academy of Management Discoveries
Academy of Management Journal
Academy of Management Learning and Education
Academy of Management Perspectives
Academy of Management Proceedings
Academy of Management Review
or
Select your citation style and then place your mouse over the citation text to select it.

SHARE

email

Usage metrics

Journal of Cerebral Blood Flow & Metabolism

AUTHORS (17)

Naohide Kurita
Kazuo Yamashiro
Takuma Kuroki
Ryota Tanaka
Takao Urabe
Yuji Ueno
Nobukazu Miyamoto
Masashi Takanashi
Hideki Shimura
Toshiki Inaba
Yuichiro Yamashiro
Koji Nomoto
Satoshi Matsumoto
Takuya Takahashi
Hirokazu Tsuji
Takashi Asahara
Nobutaka Hattori
need help?