gms | German Medical Science

Objective: Ischemic stroke is the third most common cause of death in the industrialized world. The breakdown of the neurovascular unit after ischemia leads to edema or swelling of ischemic region. In our recent study, we identified guidance molecule EphrinB2 as a key player in enhancing vascular repair and in reducing brain swelling. Here, we aim to investigate the impact of cell-specific EphrinB2 on the edema formation and blood-brain-barrier (BBB) integrity after stroke.

Methods: We have generated two different inducible cell-specific EphrinB2 knockouts. Endothelial specific EphrinB2 knockout and neuronal specific EphrinB2 knockouts were achieved by using CDH5 promotor and THY1 promotor, respectively. Cerebral infarct was induced by 45 min middle cerebral artery occlusion in both endothelial-specific and Neuron-specific EphrinB2 knockout mice lines. The success of the vascular occlusion was evaluated by T2-weighted magnetic resonance image (MRI) scans. The brains were harvested after 24 and 72h post-ischemia to immunohistologically analyze the BBB integrity, tight junction protein expression. Furthermore, the integrity of Evans blue extravasation was assessed by the administration of Evans Blue dye.

Results: Our date shows significant increase (p<0.001) in the infarct volume and edema formation in the endothelial specific EphrinB2 knockout (CDH5) when compared to neuronal-specific EphrinB2 knockout (THY1). Furthermore, reduced angiogenic activity and significantly decreased (p<0.001) endothelial-pericyte interaction was observed in CDH5 mice line 72 h post-stroke. Vastly altered tight junction protein (Claudin-5) expression and significantly increased Evans blue extravasation, confirms the substantial post-stroke BBB disruption in the endothelial EphrinB2 knockout. Both endothelial and neuronal-specific EphrinB2 knockouts had no effect on neuronal survival within 72 h post-stroke.

Conclusion: Our study reveals that the endothelial specific ephrinB2 plays a critical role in therestoration of the blood-brain barrier during the acute phase of ischemic stroke. At this stage neuronal expressed EphrinB2 is not involved in the vascular recovery.