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

Significance Sepsis results in the heparanase-mediated release of heparan sulfate oligosaccharides from the endothelial glycocalyx. In human sepsis patients, these released heparan sulfate oligosaccharides have been shown to be rich in highly sulfated domains, and their presence was associated with moderate or severe cognitive impairment. The current study uses a murine sepsis model to show that an exogenously administered highly sulfated 13 C-labeled heparan sulfate oligosaccharide, rich in highly sulfated domains, selectively targets the hippocampus. This selective targeting suggests that heparan sulfate sequestering of brain-derived neurotrophic factor in the hippocampus may impact spatial memory formation. A therapeutic strategy for selectively protecting cognition in septic patients might be developed through targeting these heparan sulfate oligosaccharides, rich in highly sulfated domains.