Wang, Haipeng, Feng, Ying, Jiang, Wei, Wang, Han, Zhang, Ruolin, Li, Guangqiang, Duan, Chao, Zhou, Yuneng, Bao, Wendai, Shui, Ke, Zhang, Min, Ai, Zhibing, Yang, Xin  ORCID: https://orcid.org/0000-0002-8429-7598, Zhou, Peiyang and Dong, Zhiqiang
2026.
Riluzole preserves brain endothelial integrity in ischemic stroke via SLC7A11-dependent GPX4 and HIF-1α/VEGFA signaling.
Cellular Signalling
142
, 112378.
10.1016/j.cellsig.2026.112378
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Abstract
Riluzole, an FDA-approved neuroprotective agent, was investigated for its therapeutic potential in ischemic stroke. Transcriptomic profiling of human brain microvascular endothelial cells (hBMECs) subjected to oxygen-glucose deprivation/reperfusion (OGD/R) identified a pivotal role for the cystine/glutamate antiporter SLC7A11. We found that riluzole activates SLC7A11, thereby triggering a dual protective mechanism: it strengthens cellular antioxidant capacity by upregulating GPX4 while simultaneously enhancing proangiogenic signaling through the HIF-1α/VEGFA pathway. Consequently, riluzole attenuated OGD/R-induced endothelial injury and, in a mouse stroke model, reduced blood–brain barrier disruption and improved neurological outcomes. Our study reveals a previously unrecognized cerebrovascular protective mechanism of riluzole, establishing SLC7A11 as its key mediator. This SLC7A11-dependent dual-pathway action represents a substantive advance in understanding riluzole's therapeutic biology beyond its established roles in the central nervous system.
| Item Type: | Article |
|---|---|
| Date Type: | Publication |
| Status: | Published |
| Schools: | Schools > Engineering |
| Publisher: | Elsevier BV |
| ISSN: | 0898-6568 |
| Date of First Compliant Deposit: | 13 February 2026 |
| Date of Acceptance: | 12 January 2026 |
| Last Modified: | 13 Feb 2026 10:00 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/184533 |
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