# Circulating Extracellular Vesicles as Biomarkers of Postoperative Delirium

> **NIH NIH R21** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $268,500

## Abstract

Program Director/Principal Investigator (Last, First, Middle): Crosby, Gregory J
Abstract
Delirium, an acute confusional state, is one of the most common postoperative complications in older surgical
patients and is associated with suboptimal recovery and high mortality. Yet, its cause is uncertain, therapeutic
options are limited, and there are no reliable biomarkers. We hypothesize that circulating extracellular vesicles
(EVs) and their cargo can identify patients at risk for or who experience postoperative delirium and carry new
biomarkers for the syndrome. EVs are small (30-500 nm) bilipid particles that are shed or secreted by most
cells, including those of the immune and central nervous systems, are present in blood, have surface markers
of the parent cell, and carry a cargo of RNA and proteins. EVs are involved in numerous physiological and
pathological processes and increasingly are being researched as biomarkers of many age-related conditions
and diseases. No research, however, has investigated the relationship between delirium and circulating EVs.
We will test our hypothesis that postoperative delirium is associated with changes in the concentration, size,
and cargo of blood-borne EVs using biobanked plasma samples from a well-characterized cohort of older,
elective spine surgery patients, and then confirm the results in a prospective replication cohort. In Aim 1, we
will sort and profile EVs in plasma using serial centrifugation, affinity columns, Nanoparticle Tracking and Nano
FACS and compare EV abundance and size in preoperative and postoperative samples from patients that did
or did not develop delirium postoperatively, and do the same using just the EV population derived from
neurons or glia as determined by immunoaffinity methods. In Aim 2, we will investigate the RNA and protein
cargo of the total EV population and CNS-derived fraction in plasma using multiplexed RNA panels and
targeted ELISAs and Western blots, focusing on pathways implicated in delirium such as inflammation,
endothelial cell / blood brain barrier function, stress, and neurodegeneration. The outcome of this research will
be original information about the relationship between circulating extracellular vesicles and postoperative
delirium, new insights into the role of EVs and their contents in the pathogenesis of this common, highly morbid
syndrome, and insight into the potential of an EV-based “liquid biopsy” to discover novel biomarkers that could
improve the care of older surgical patients at high risk for delirium.
OMB No. 0925-0001/0002 (Rev. 03/16 Approved Through 10/31/2018) Page Continuation Format Page

## Key facts

- **NIH application ID:** 9870857
- **Project number:** 5R21AG061696-02
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** GREGORY CROSBY
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $268,500
- **Award type:** 5
- **Project period:** 2019-02-15 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9870857

## Citation

> US National Institutes of Health, RePORTER application 9870857, Circulating Extracellular Vesicles as Biomarkers of Postoperative Delirium (5R21AG061696-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9870857. Licensed CC0.

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