Modeling Ischemia-Reperfusion Injury in Stroke Using the BBB Chip

Area of Science:

• Neuroscience
• Biomedical Engineering
• Pathology

Background:

• Ischemic stroke is a major global cause of disability.
• Current humanized models are insufficient for studying stroke pathogenesis and drug development.
• Reperfusion injury is a critical aspect of ischemic stroke that requires better models.

Purpose of the Study:

• To develop a humanized microfluidic organ-on-a-chip model for simulating ischemic stroke reperfusion injury.
• To investigate the physiological and pathological responses in the developed ischemic stroke model.
• To identify potential therapeutic drugs for ischemic stroke treatment.

Main Methods:

• Utilized a high-throughput microfluidic chip device to create an in vitro ischemic stroke model.
• Simulated ischemia-reperfusion injury to mimic patient conditions.
• Performed transcriptome sequencing to analyze gene expression changes.
• Conducted drug screening experiments using acetazolamide, edaravone, and fasudil.

Main Results:

• The model successfully recapitulated key injury characteristics of ischemic stroke, including blood-brain barrier destruction, cell apoptosis, and mitochondrial dysfunction.
• Transcriptome analysis revealed significant dysregulation in pathways related to autophagy, oxidative stress, and angiogenesis.
• Acetazolamide, edaravone, and fasudil demonstrated significant damage reduction in the model.

Conclusions:

• The microfluidic organ-on-a-chip model effectively mimics ischemic stroke reperfusion injury.
• This model provides a valuable platform for advancing pathogenesis research and therapeutic drug development for ischemic stroke.
• The findings support the potential of this model to improve treatment strategies for millions affected by stroke worldwide.