# Radiographic markers and therapeutic targets of cerebral edema after SAH

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2024 · $571,202

## Abstract

PROJECT SUMMARY/ABSTRACT
Subarachnoid Hemorrhage (SAH) is a type of hemorrhagic stroke that affects ~500,000 people annually world-
wide and causes significant mortality and long-term disability. Severe cerebral edema (CE) occurs in ~30-40%
of SAH and contributes to poor long-term outcomes. Although CE has been implicated as an important
pathophysiologic process after SAH, CE targeted therapeutics have not been explored. In this proposal, we
address important barriers to the development of therapies targeting CE by 1) using a Dual-energy CT (DECT)
based method for measuring brain water content (BWC) to develop a validated measure of CE after SAH and 2)
identifying the role of miR-335-3p and miR-5585-5p in the mechanisms of CE after SAH. We have previously
developed surrogate markers of CE using sulcal effacement measurements on computed tomography (CT)
scans [Selective Sulcal Volume (SSV) and the Subarachnoid Hemorrhage Early Brain Edema Score (SEBES)].
Using these markers, combined with miRNA and proteomic analyses, our preliminary data show elevated
miRNAs (miR-335p and miR-5585) and decreased proteins (including SCARA5, GPNMB, and NTRK2) in SAH
patients with severe sulcal effacement. These miRNAs are predicted to downregulate Na+/K+ATPase (NKATP)
expression as well as the proteins found to be decreased after SAH. NKATP is important for maintenance of
cellular membrane potential and has been shown to be downregulated after SAH. Disruption of NKATP has been
shown to cause cellular swelling which can lead to CE. Our preliminary data shows elevations in miR-335 and
miR-5585, decreased Na/K ATPase α-1 subunit (an essential subunit of NKATP) and increased cellular edema
in an in vitro SAH model. We also found miR-335 and miR-5585 elevations in brain tissue in an in vivo model
with associated CE measured by MRI and ex-vivo methods. Despite the utility of SSV and SEBES, these markers
only measure the sulcal spaces in the brain and are indirect measures of CE, limiting their utility. We have found
that CE can be measured in brain parenchyma using DECT. This measure of brain parenchymal water content
will address the limitations of indirect markers. We will employ a “bed-to-bench” approach, where a combination
of DECT BWC techniques, plasma/cerebrospinal fluid samples and in vivo and in vitro models will be used to
test the following specific aims. Aim 1 will test whether BWC is predictive of in-hospital complications and long-
term outcomes. We will test if miR-335 and miR-5585 (markers of sulcal effacement) are also markers of BWC
and if they are predictive of clinical outcomes. Aim 2 will investigate the mechanism of miR-335 and miR-5585
related CE and if antagonism can ameliorate their detrimental effects in an in vitro and in vivo model. We will
perform the clinical study across two centers: UTHealth Houston and University of Maryland Medical Center.
The completion of our proposal will establish a validated radiographic technique that represents CE...

## Key facts

- **NIH application ID:** 10883067
- **Project number:** 1R01NS131469-01A1
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Huimahn Alex Choi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $571,202
- **Award type:** 1
- **Project period:** 2024-05-01 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10883067

## Citation

> US National Institutes of Health, RePORTER application 10883067, Radiographic markers and therapeutic targets of cerebral edema after SAH (1R01NS131469-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10883067. Licensed CC0.

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