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Updated: Jan 10, 2026
An In Vivo Assessment of Blood-Brain Barrier Disruption in a Rat Model of Ischemic Stroke
Published on: March 11, 2018
Impact of direct oral anticoagulants on blood-brain barrier integrity
Kei Sato1,2, Yoichi Morofuji1,3, Dohgu Shinya4
1Department of Neurosurgery, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
Introduction:
In cerebral infarction, major prognostic factors include hemorrhagic transformation and cerebral edema, both partially associated with blood-brain barrier (BBB) disruption. Anticoagulation therapy, especially with direct oral anticoagulants (DOACs), is linked to these outcomes, suggesting that the effect of DOACs on BBB integrity may influence stroke prognosis and recovery.
Methods:
Two in vitro BBB models-a monolayer model and a co-culture model-were constructed using rat brain endothelial cells (RBECs), pericytes, and astrocytes. Each model was treated with one of three DOACs: apixaban, rivaroxaban, or dabigatran. Transendothelial electrical resistance (TEER) was measured to assess BBB integrity.
Results:
In the monolayer model, TEER increased significantly with 10 μM apixaban and decreased significantly with 50 μM dabigatran. In the co-culture model, a significant TEER reduction was observed in the 10 μM dabigatran group, while no significant differences were found for apixaban or rivaroxaban.
Conclusion:
These preliminary findings suggest that apixaban may help preserve BBB integrity, while dabigatran at certain concentrations may compromise it.
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