Neuroinflammation and immunothrombosis transcriptional patterns in CCM lesions revealed by spatial transcriptomics

Cerebral cavernous malformation (CCM) immunothrombosis is the connection between immune cells, platelet activation, coagulation cascades and astrocyte-CCM endothelium interaction, and its excessive activation may contribute to neurological disabilities in CCM disease. We characterized the spatial organization of CCM immunothrombosis observed in Pdcd10BECKObrains under normoxic conditions using the murine 10X Genomics Visium Spatial Gene Expression platform. Brain endothelial cell-specific conditional Pdcd10-knockout mice were generated by crossing a brain endothelial tamoxifen-regulated Cre recombinase (Slco1c1-iCreERT2) strain with loxP-flanked Pdcd10 (Slco1c1-iCreERT2; Pdcd10fl/fl). On a postnatal day 1 (P1), mice were administered 50 μg of 4-hydroxy-tamoxifen (H7904, Sigma-Aldrich) by intragastric injection to induce genetic inactivation of endothelial CCM3 gene in littermates with Slco1c1-iCreERT2;Pdcd10fl/fl (Pdcd10BECKO) and Pdcd10fl/fl mice were used as littermate controls. P65 Pdcd10BECKO mice, with exacerbated lesions under normoxic conditions was used for analysis.