# GENETICS AND PREDICTION OF CEREBRAL EDEMA AFTER HEMISPHERIC STROKE

> **NIH NIH K23** · WASHINGTON UNIVERSITY · 2020 · $179,079

## Abstract

PROJECT SUMMARY
The greatest contributor to neurological deterioration in the first week after stroke is development of brain
swelling around the area of infarction. However, only half of those with large strokes develop malignant
cerebral edema sufficient to compress adjacent brain structures and threaten survival. Clinical factors
including stroke size do not explain the degree of edema that develops. Instead, it is likely that intrinsic
differences in cellular mechanisms and biologic pathways activated after stroke contribute to the observed
heterogeneity in swelling. We believe that identifying the genetic factors underlying this biologic variability
will provide important actionable knowledge that could lead to improved targeted treatments for edema
and better prediction of who is at risk.
In order to study the biology of cerebral edema, we need to capture the full spectrum of its severity with an
accurate and quantifiable measure of swelling. We have developed a novel marker of edema severity that
measures amount of CSF pushed out of the brain as the stroke swells. This measure (∆CSF) has been
validated in a preliminary study and we will now refine it by modeling ∆CSF at any time point (whenever
CT is performed, using 400 scans already acquired coupled to an automated algorithm we have developed).
This intermediate phenotype will capture rate of edema formation and be able to quantify which patients
have relatively malignant trajectories vs. those who are relatively protected (given their stroke severity and
infarct size) against developing edema.
We are continuing to acquire CT scans from subjects enrolled in a large multi-site acute stroke study that
already has almost 3,000 patients genotyped (supported by my primary mentor, Jin-Moo Lee’s R01 grant
studying neurological improvement after stroke). We will measure rate of ∆CSF in this larger (and still
expanding) cohort and quantify the residual variability (adjusting for clinical covariates) in order to
ascertain for potential genetic component. Our genomic analyses of this edema endophenotype will include
GCTA, a means of estimating total heritability, followed by genome-wide association study to identify
common polymorphisms associated with our continuous measure of edema. This unbiased discovery
approach will be supplemented by modern evolving means of uncovering rare variants and genetic
pathways that could further explain heritability of edema and provide refined biologic targets. I will also
learn to evaluate the functional significance of any potential genetic markers identified with these analyses.
I will be mentored in these bioinformatics and quantitative genomic methods by Dr. Carlos Cruchaga, a
geneticist with special expertise in dissecting complex traits using quantitative endophenotypes (e.g. CSF
tau levels as intermediate phenotypes for Alzheimer’s disease).
This project represents not only the first study of the genetic basis of cerebral edema but also a first step in
a r...

## Key facts

- **NIH application ID:** 10020442
- **Project number:** 5K23NS099440-04
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Rajat Raj Dhar
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $179,079
- **Award type:** 5
- **Project period:** 2017-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10020442

## Citation

> US National Institutes of Health, RePORTER application 10020442, GENETICS AND PREDICTION OF CEREBRAL EDEMA AFTER HEMISPHERIC STROKE (5K23NS099440-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10020442. Licensed CC0.

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