# Neurovascular Protection by Adropin in Ischemic Stroke

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2021 · $345,214

## Abstract

ABSTRACT
Adropin is a recently identified and highly conserved polypeptide abundantly expressed in the brain. Adropin
plays a critical role in the regulation of endothelial function, insulin sensitivity, and metabolism. Recent findings
from our group and others reveal that adropin can significantly reduce endothelial permeability in rat brain and
human vascular endothelial cells. Clinical studies show a significant association between low plasma levels of
adropin and endothelial dysfunction in several human diseases. Endothelial dysfunction is one of the critical
factors contributing to the pathogenesis of ischemic stroke. Deficient production of nitric oxide (NO) by
endothelial nitric oxide synthase (eNOS) is a key factor contributing to endothelial dysfunction in diabetes,
obesity, and hyperlipidemia, which are important risks factors for stroke. Our hypothesis is that adropin confers
protection against ischemic stroke injury by reducing damage to the blood-brain barrier (BBB)/neurovascular
unit. Our overall goal in this proposal is to demonstrate the protective role of adropin in ischemic stroke and
investigate the underlying molecular mechanisms of this protection. Our preliminary data support this hypothesis
by showing that treatment with synthetic adropin dramatically reduces brain injury in a mouse stroke model,
which was associated with a significant increase in eNOS phosphorylation and reduced BBB damage. Moreover,
adropin protection was completely abolished in eNOS deficient mice suggesting an eNOS-dependent
mechanism underlying the protective effects of adropin in stroke. Aim 1 is to determine the effects of adropin
treatment on infarct size and long-term functional recovery in a mouse model of ischemic stroke. In Aim 2, we
will determine the ability of adropin to reduce the detrimental effects of endothelial dysfunction, oxidative stress,
and neuroinflammation on BBB function following ischemic stroke. In Aim 3, we will test the neuroprotective
efficacy of adropin in relation to age, sex, species, and comorbid conditions (obesity and diabetes). It is our
expectation that this study will provide significant knowledge on the protective efficacy of adropin in ischemic
stroke. Such results would be expected to have an important positive impact, since they would set the stage for
expanded preclinical work on the protective efficacy of adropin in cerebral ischemia, and would identify novel
and much-needed approaches to reduce the devastating consequences of neurovascular injury after stroke.

## Key facts

- **NIH application ID:** 10161626
- **Project number:** 5R01NS103094-04
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Eduardo Jesus Candelario-Jalil
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $345,214
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10161626

## Citation

> US National Institutes of Health, RePORTER application 10161626, Neurovascular Protection by Adropin in Ischemic Stroke (5R01NS103094-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10161626. Licensed CC0.

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