# Insights into the potential pathogenesis and therapeutic implications of ferroptosis in brain microvascular endothelial cells during stroke

## TL;DR

This review explores how ferroptosis in brain microvascular endothelial cells contributes to stroke injury and suggests potential therapies to target this process.

## Contribution

The paper systematically examines ferroptosis in brain microvascular endothelial cells during stroke, highlighting novel molecular pathways and therapeutic strategies.

## Key findings

- Ferroptosis in BMECs contributes to BBB disruption and cerebral edema after stroke.
- Multiple signaling pathways regulate BMEC ferroptosis, including Meg3/p53/GPX4 and TEAD1/MMP3.
- Therapeutic strategies like iron chelators and nanodelivery systems may target BMEC ferroptosis.

## Abstract

Brain microvascular endothelial cells (BMECs) constitute the core component of the Blood-Brain Barrier (BBB), whose structural and functional integrity is crucial for maintaining central nervous system homeostasis. In recent years, ferroptosis—a novel iron-dependent lipid peroxidation-driven cell death pathway—has been demonstrated to play a pivotal role in secondary brain injury following stroke. However, current research predominantly focuses on ferroptosis in neurons and glial cells, with insufficient attention given to the mechanisms underlying BMEC ferroptosis in stroke pathogenesis. This review systematically examines the pivotal role of BMEC ferroptosis in the development of both ischemic and hemorrhagic strokes, elucidating its multiple pathways for exacerbating brain injury: compromising BBB integrity, triggering vasogenic cerebral edema, intensifying neuroinflammation, and promoting hemorrhagic transformation. The article highlights the molecular mechanisms of signaling pathways—including Meg3/p53/GPX4, TEAD1/MMP3, SESN2/System Xc−/GPX4, and SP1/TNFSF9/SLC3A2—in regulating BMEC ferroptosis. It summarizes multidimensional therapeutic strategies encompassing iron chelators, genetic/molecular interventions (e.g., FGF2, p23, METTL3, lncRNA H19), novel nanodelivery systems (e.g., RosA-LIP), and selenium compounds (SeMC). This study aims to provide new insights into vascular unit injury after stroke and establish theoretical foundations and translational directions for developing neuroprotective therapies targeting ferroptosis in BMECs.