ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2024
Endothelial lincRNA-p21 alleviates cerebral ischemia/reperfusion injury by maintaining blood-brain barrier integrity.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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8 citing papers in PubMed, 9 citations in OpenAlex.
- Nitric Oxide Donor Alleviates Cardiac Arrest Induced Blood Brain Barrier Injury by Inhibiting HMGB1-ATG5 Mediated Endothelial Autophagy.Cellular and molecular neurobiology · 2026Article
- Targeting epigenetic remodeling of the blood-brain barrier: current knowledge for drug therapy.Epigenomics · 2026Review
- Novel mechanism of neuronal hypoxia response: HIF-1α/STOML2 mediated PINK1-dependent mitophagy activation against neuronal injury.Cell death discovery · 2026Article
- The role of ROCK1/MLC/NMMHC IIA-actin signaling in ischemic stroke-induced blood-brain barrier disruption: implications for therapeutic intervention.Cellular and molecular life sciences : CMLS · 2025Article
- Review
- Targeting CX3CR1 Signaling Dynamics: A Critical Determinant in the Temporal Regulation of Post-Stroke Neurorepair.Brain sciences · 2025Review
- Piezo1 disrupts blood-brain barrier via CaMKII/Nrf2 in ischemic stroke.Cellular and molecular life sciences : CMLS · 2025Article
- High-altitude exposure and ischemic stroke: pathophysiological mechanisms and current perspectives.Frontiers in neurologyReview
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Blood-brain barrier (BBB) disruption is increasingly recognized as an early contributor to the pathophysiology of cerebral ischemia/reperfusion (I/R) injury, and is also a key event in triggering secondary damage to the central nervous system. Recently, long non-coding RNA (lncRNA) have been found to be associated with ischemic stroke. However, the roles of lncRNA in BBB homeostasis remain largely unknown. Here, we report that long intergenic non-coding RNA-p21 (lincRNA-p21) was the most significantly down-regulated lncRNA in human brain microvascular endothelial cells (HBMECs) after oxygen and glucose deprivation/reoxygenation (OGD/R) treatment among candidate lncRNA, which were both sensitive to hypoxia and involved in atherosclerosis. Exogenous brain-endothelium-specific overexpression of lincRNA-p21 could alleviate BBB disruption, diminish infarction volume and attenuate motor function deficits in middle cerebral artery occlusion/reperfusion (MCAO/R) mice. Further results showed that lincRNA-p21 was critical to maintain BBB integrity by inhibiting the degradation of junction proteins under MCAO/R and OGD/R conditions. Specifically, lincRNA-p21 could inhibit autophagy-dependent degradation of occludin by activating PI3K/AKT/mTOR signaling pathway. Besides, lincRNA-p21 could inhibit VE-cadherin degradation by binding with miR-101-3p. Together, we identify that lincRNA-p21 is critical for BBB integrity maintenance, and endothelial lincRNA-p21 overexpression could alleviate cerebral I/R injury in mice, pointing to a potential strategy to treat cerebral I/R injury.
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