Circulating heparin oligosaccharides rapidly target the hippocampus in sepsis, potentially impacting cognitive functions.

ABSTRACT: Sepsis induces heparanase-mediated degradation of the endothelial glycocalyx, a heparan sulfate-enriched endovascular layer critical to vascular homeostasis, releasing highly sulfated domains of heparan sulfate into the circulation. These domains are oligosaccharides rich in heparin-like trisulfated disaccharide repeating units. Using a chemoenzymatic approach, an undecasaccharide containing a uniformly ¹³C-labeled internal 2-sulfoiduronic acid residue was synthesized on a p-nitrophenylglucuronide acceptor. Selective periodate cleavage afforded a heparin nonasaccharide having a natural structure. This ¹³C-labeled nonasaccharide was intravenously administered to septic (induced by cecal ligation and puncture, a model of polymicrobial peritonitis-induced sepsis)

SUBMITTER: Zhang X 

PROVIDER: S-EPMC6511061 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature