Blood brain barrier breakdown was found in non-infarcted area after 2-h MCAO

Area of Science:

• Neuroscience
• Cerebrovascular Research
• Stroke Pathophysiology

Background:

• The blood-brain barrier (BBB) is crucial for brain homeostasis and can be compromised during stroke reperfusion.
• Early BBB damage is a potential precursor to hemorrhagic transformation, but its precise timing and relationship with tissue injury remain unclear.

Purpose of the Study:

• To investigate the temporal and spatial relationship between early BBB damage and ischemic tissue injury following middle cerebral artery occlusion (MCAO).
• To identify molecular mechanisms underlying BBB disruption during the early reperfusion phase after stroke.

Main Methods:

• Rats underwent 2-hour MCAO followed by 10-minute reperfusion, with Evan's blue used to detect BBB leakage.
• Brain tissue was analyzed for BBB damage and infarct size using TTC staining.
• Neuronal degeneration was assessed with Fluoro Jade B staining.
• Expression and degradation of tight junction proteins (occludin, claudin-5) were examined.
• The effect of matrix metalloproteinase (MMP) inhibitor GM6001 on BBB damage was evaluated.

Main Results:

• Ischemic tissue injury was observed starting from the second brain slice, while BBB leakage began from the fifth slice, indicating a spatial mismatch.
• Neuronal degeneration was prominent in the ischemic cortex and dorsal striatum.
• MCAO induced degradation of occludin but not claudin-5 in the ischemic hemisphere.
• GM6001 pretreatment significantly reduced occludin degradation and BBB leakage.

Conclusions:

• A temporal and spatial "mismatch" exists between early ischemic tissue injury and BBB leakage after 2-hour MCAO.
• Matrix metalloproteinase-2 (MMP-2) plays a role in the differential degradation of occludin, contributing to BBB damage during early reperfusion.