# Role of nitro-fatty acids in BBB stabilization and post-stroke neurovascular protection

> **NIH VA I01** · VETERANS HEALTH ADMINISTRATION · 2021 · —

## Abstract

Stroke is one of the major medical concerns for United States veterans. At least 15,000 veterans are
hospitalized every year for stroke and most survivors live with long-term neurological impairments.
Unfortunately, development of effective therapies is seriously limited. Extensive studies have shown that BBB
breakdown promotes a devastating cascade of events, contributing to transmigration of peripheral immune
cells, cerebral inflammatory responses, edema, hemorrhagic transformation, neuronal loss and eventual
neurological deficits after cerebral ischemia/reperfusion (I/R). Thus, it is necessary to identify mechanisms and
develop effective therapeutic strategies that protect BBB integrity and prevent permanent neurovascular injury
after I/R.
 Nitro-oleic acid (OA-NO2), a nitroalkene formed in nitric oxide (NO)-dependent oxidative reactions, has
been found in human plasma and is thought to be a novel cell signaling mediator that regulates physiological
functions in multiple cell types. It has been shown that OA-NO2 is an endogenous peroxisome proliferator-
activated receptor-γ (PPARγ) ligand and activates PPARγ at physiological levels. Recent data have shown that
OA-NO2 significantly reduces peripheral vascular inflammation and endoluminal vessel injury. Provocatively,
several publications have documented that OA-NO2 is increased under ischemia-reperfusion conditions and
attenuates cardiac or renal ischemia/reperfusion injury. However, the functional significance and molecular
mechanisms of OA-NO2 in regulating cerebrovascular pathogenesis, in particular BBB disruption, and resultant
neurological outcomes remain unexplored in ischemic stroke.
 In our preliminary studies, we have recently identified for the first time that intravenous (i.v.) administration
of OA-NO2 leads to reuced BBB leakage, smaller brain infarction, and improved neurobehavior in mice after
middle cerebral artery occlusion (MCAO). Moreover, we found that OA-NO2 significantly elevates the mRNA
and protein expression of major BBB tight junctions in cultured brain microvascular endothelial cells (BMECs).
These findings suggest that nitroalkenes may play a critical neurovascular protective role in ischemic brain
damage. In this proposal, we will test our Central Hypothesis that OA-NO2 preserves BBB integrity after I/R
via activation of PPARγ and other signaling pathways, attenuates BBB disruption and subsequent
pathological cascades, thereby eliciting neurovascular protection. Three aims will be performed in this
proposal. Aim 1: Define the role of OA-NO2 in BBB dysfunction/recovery and brain injury after ischemic stroke;
Aim 2: Elucidate the mechanisms of OA-NO2 regulation of post-stroke BBB dysfunction/recovery; Aim 3:
Explore systematic delivery of OA-NO2 as a potential BBB stabilizing therapy in ischemic stroke. Elucidating
the molecular mechanisms of OA-NO2-mediated BBB stabilization and recovery may lead us to discover novel
pharmaceutical approaches for the effective treatme...

## Key facts

- **NIH application ID:** 10007200
- **Project number:** 1I01BX004837-01A1
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** Kejie Yin
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2020-10-01 → 2024-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10007200

## Citation

> US National Institutes of Health, RePORTER application 10007200, Role of nitro-fatty acids in BBB stabilization and post-stroke neurovascular protection (1I01BX004837-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10007200. Licensed CC0.

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