# Neurovascular protection by adropin in acute neural injury from subarachnoid hemorrhage

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2022 · $386,193

## Abstract

ABSTRACT
Acute neural injury from subarachnoid hemorrhage (SAH)-associated cerebral infarction occurs in 30-40% of
patients who survive the initial hemorrhage, leads to death and disability, and most strongly correlates with 3-
month outcome. There is also a significant rate of long-term cognitive deficits. Current understanding of the
pathophysiology of post-SAH cerebral infarction points to injury cascades involving decreased nitric oxide (NO)
bioavailability and oxidative stress. Under normal conditions, NO signaling pathways regulate cerebral blood
flow by mediating cerebral vasodilation and inhibiting platelet adhesion. However, with SAH, red blood cells
lyse and release hemoglobin, which is a spasmogenic. Hemoglobin scavenges NO; stimulates production of a
nitric oxide synthase (NOS) inhibitor (ADMA); and generates reactive oxygen species (ROS) and nitrogen
species (RNS). We believe the recently-identified peptide hormone adropin is a promising therapeutic target for
post-SAH cerebral infarction. Our group and others have shown adropin is abundantly expressed in the brain,
regulates the endothelial nitric oxide synthase (eNOS) pathway, correlates with markers of oxidative stress,
and reduces brain endothelial permeability in response to simulated ischemia. Our hypothesis is that adropin
confers protection against acute neural injury from post-SAH cerebral infarction. Our overall goal in this
proposal is to demonstrate the protective role of adropin in SAH and investigate the underlying molecular and
cellular mechanisms of this protection. Our preliminary data support this hypothesis by showing that SAH
decreases brain adropin expression, and that endogenous adropin overexpression by transgenic mice with a
β-actin-driven adropin transgene (AdrTg) or treatment with synthetic adropin in the SAH model reduces
cerebral edema, preserves tight junction protein expression, abolishes microthrombosis, increases eNOS
phosphorylation, prevents cerebral vasospasm, and inhibits neuronal apoptosis. Aim 1 is to determine whether
adropin confers protection against acute neural injury after SAH when given in a clinically translatable
timepoint after SAH. In Aim 2, we will study mediators that regulate Enho gene expression in the setting of
SAH. In Aim 3, we will study whether adropin neurovascular protection is mediated via eNOS activity. We
expect this study will provide novel knowledge on adropin-mediated protection against acute neural injury after
SAH. The significance of this study is that it is directly translatable and the first to investigate the fundamentals
of adropin regulation in brain endothelial cells after SAH. This study will provide the preclinical data for a Phase
1/2 human clinical trial in SAH patients.

## Key facts

- **NIH application ID:** 10520313
- **Project number:** 1R01NS124620-01A1
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Brian Lim Hoh
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $386,193
- **Award type:** 1
- **Project period:** 2022-08-15 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10520313

## Citation

> US National Institutes of Health, RePORTER application 10520313, Neurovascular protection by adropin in acute neural injury from subarachnoid hemorrhage (1R01NS124620-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10520313. Licensed CC0.

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