# Targeting circulating endothelial glycocalyx fragments to reduce septic encephalopathy

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2020 · $438,956

## Abstract

PROJECT SUMMARY/ABSTRACT
Sepsis is a major cause of death and morbidity in both developing and industrialized societies. While great
effort has been dedicated to the study of acute organ injury during sepsis, little is known about the mechanisms
underlying the chronic morbidities faced by sepsis survivors. One such morbidity is septic neurocognitive
dysfunction (also known as chronic septic encephalopathy), a common, severe illness characterized by the
accelerated onset of dementia. Recently, the laboratories of Dr. Eric Schmidt (with extensive expertise in the
study of sepsis and glycobiology) and Dr. Paco Herson (with extensive expertise in the study of brain injury)
have partnered to establish a mouse model of septic neurocognitive dysfunction. This model has allowed the
Schmidt and Herson laboratories to explore a novel hypothesis: that septic degradation of the systemic
endothelial glycocalyx (a heparan sulfate (HS)-rich layer lining the vascular lumen) releases biologically-active,
circulating HS fragments capable of penetrating the hippocampus and disrupting growth factor signaling
pathways implicated in cognition. This newly-created collaboration will explore this hypothesis by performing
ex vivo electrophysiological studies of living mouse hippocampi, in vivo mechanistic investigations of
neurocognitive dysfunction in mouse survivors of endotoxemia or polymicrobial sepsis, and mass spectrometry
studies of human plasma samples collected from a cohort of septic patients who underwent rigorous testing of
neurocognitive function after sepsis resolution. This novel proposal, which departs from the
“hyperinflammatory” dogma of septic organ injury, promises to identify a mechanistic pathway that is not only
responsible for the development of septic neurocognitive dysfunction, but is amenable to therapeutic targeting
even in established sepsis.

## Key facts

- **NIH application ID:** 9922971
- **Project number:** 5R01GM125095-04
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Paco S Herson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $438,956
- **Award type:** 5
- **Project period:** 2017-07-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9922971

## Citation

> US National Institutes of Health, RePORTER application 9922971, Targeting circulating endothelial glycocalyx fragments to reduce septic encephalopathy (5R01GM125095-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9922971. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*