Abstract
Ischemic stroke is a leading cause of disability worldwide and poses a serious threat to public health, affecting tens of millions of people all over the world per year. The lack of a humanized organ model reflecting the real situation of patients has quite limited the pathogenesis research and therapeutic drug development of ischemic stroke. In this study, we developed an ischemic stroke model based on a high-throughput microfluidic chip device, simulating ischemia-reperfusion injury in an ischemic stroke. In this ischemic stroke model, we observed a series of injury characteristics, including significant blood-brain barrier (BBB) destruction, cell apoptosis, and mitochondrial dysfunction. Transcriptome sequencing analysis showed that the expression of genes involved in autophagy, oxidative stress, angiogenesis, and other related pathways was significantly dysregulated in the ischemic stroke model. Drug screening experiments revealed that acetazolamide (AZA), edaravone (EDA), and fasudil (FAS) could significantly reduce the damage in an ischemic stroke model. Overall, the ischemic stroke model recapitulated the physiological and pathological responses of ischemic stroke, and it was innovative that our model focused on reperfusion injury using microfluidic organ-on-a-chip technology. This ischemic stroke brain model holds promise for advancing the development and testing of therapeutic drugs for ischemic stroke, thus contributing to the evolution of treatment strategies.