Activation of Wnt signaling mitigates blood-brain barrier disruption by inhibiting vesicular transcytosis after traumatic brain injury in mice

This study aims to elucidate the impact of Wnt/β-catenin signaling on cerebrovascular vesicular transcytosis following TBI. In this experiment, adult male wild-type (WT) C57BL/6 mice underwent various interventions. TBI was induced utilizing the controlled cortical impact technique. Post-TBI, mice were administered either an inhibitor or an agonist of Wnt signaling via intraperitoneal injection. Recombinant adeno-associated virus (rAAV) was administered intracerebroventricularly to modulate the expression of the CAV-1 inhibitory protein, Major facilitator superfamily domain-containing 2a (Mfsd2a). This research utilized Evans blue assay, Western blot analysis, immunofluorescence, transmission electron microscopy, and neurobehavioral assessments. Post-TBI observations revealed substantial increases in macromolecule (Evans blue and albumin) leakage, CAV-1 transport vesicle count, astrocyte end-feet edema, and augmented aquaporin-4 (AQP4) expression, culminating in BBB disruption. The findings indicate that Wnt signaling pathway inhibition escalates CAV-1 transport vesicle activity and aggravates BBB compromise. Conversely, activating this pathway could alleviate BBB damage by curtailing CAV-1 vesicle presence. Post-TBI, there is a diminution in Mfsd2a expression, which is directly influenced by the modulation of WNT signals. Employing a viral approach to regulate Mfsd2a, we established that its down-regulation undermines the protective benefits derived from reducing CAV-1 tran...
Source: Experimental Neurology - Category: Neurology Authors: Source Type: research