Circular RNA circCCDC9 alleviates ischaemic stroke ischaemia/reperfusion injury via the Notch pathway

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Stroke remains a primary cause of mortality and disability globally.
• The intricate pathophysiological mechanisms underlying stroke are not fully elucidated.
• Understanding novel molecular players is crucial for developing effective stroke therapies.

Purpose of the Study:

• To investigate the role of circular RNA CCDC9 (circCCDC9) in the pathogenesis of ischemic stroke.
• To explore the therapeutic potential of circCCDC9 in a mouse model of transient middle cerebral artery occlusion (tMCAO).

Main Methods:

• Utilized the tMCAO mouse model to induce ischemic stroke.
• Assessed the expression levels of circCCDC9 in brain tissues.
• Evaluated blood-brain barrier integrity using Evans blue and brain water content.
• Measured nitrite content and endothelial nitric oxide synthase (eNOS) expression.
• Quantified apoptosis markers (Caspase-3, Bax/Bcl-2 ratio) and Notch signaling pathway components (Notch1, NICD, Hes1).

Main Results:

• circCCDC9 expression was significantly reduced in tMCAO mouse brains.
• Overexpression of circCCDC9 ameliorated blood-brain barrier damage and reduced brain water content.
• circCCDC9 restoration normalized nitrite content and eNOS expression.
• Overexpression of circCCDC9 suppressed apoptosis and inhibited the Notch1 signaling pathway.
• Knockdown of circCCDC9 exacerbated apoptosis and activated the Notch1 pathway.

Conclusions:

• circCCDC9 plays a protective role in acute ischemic stroke.
• Overexpression of circCCDC9 safeguards the blood-brain barrier and inhibits apoptosis via Notch1 pathway suppression.
• circCCDC9 represents a promising therapeutic target for cerebrovascular protection in ischemic stroke.