Conclusions
The rearrangement of PDGFRβ(+) and vascular NG2DsRed cells after SE suggests a possible involvement of pericytes in the cerebrovascular modifications observed in epilepsy. The functional role of vascular-parenchymal PDGFRβ(+) cell redistribution and the relevance of a pericyte response to SE remain to be fully elucidated.
Methods
NG2DsRed mice were used to visualize cerebrovascular pericytes. The pattern of vascular and parenchymal distributions of platelet-derived growth factor receptor beta (PDGFRβ) cells was evaluated by immunohistochemistry. Status epilepticus was induced in NG2DsRed or C57BL/6J mice by intraperitoneal kainic acid (KA). Animals were perfused intracardially using FITC-Dextran or FITC-Albumin to visualize the cerebrovasculature. Colocalization was performed between NG2DsRed, PDGFRβ and microglia IBA-1. Confocal 3D vessel reconstruction was used to visualize changes in cell morphology and position. PDGFRβ expression was also evaluated in vitro using organotypic hippocampal cultures (OHC) treated with kainic acid to induce seizure-like activity. Co-localization of PDGFRβ with the vascular marker RECA-1 and NG2 was performed. Finally, we assessed the expression of PDGFRβ in brain specimens obtained from a cohort of patients affected by drug resistant epilepsy compared to available autoptic brain.
Purpose
The role of cerebrovascular dysfunction in seizure disorders is recognized. Blood-brain barrier (BBB) damage in epilepsy has been linked to endothelial and glial pathophysiological changes. Little is known about the involvement of pericytes, a cell type that contributes to BBB function.
Results
In vivo, severe status epilepticus (SE) altered NG2DsRed vascular coverage. We found dishomogenous NG2DsRed perivascular ramifications after SE and compared to control. Concomitantly, PDGFRβ(+) cells re-distributed towards the cerebrovasculature after severe SE. Cerebrovascular NG2DsRed partially colocalized with PDGFRβ(+) while parenchymal PDGFRβ(+) cells did not colocalize with IBA-1(+) microglia. Using in vitro OHC we found decreased NG2 vascular staining and increased PDGFRβ(+) ramifications associated with RECA-1(+) microvessels after seizure-like activity. Cellular PDGFRβ and NG2(+) colocalization was observed in the parenchyma. Finally, analysis of human TLE brains revealed perivascular and parenchymal PDGFRβ(+) cell distributions resembling the murine in vivo and in vitro results. PDGFRβ(+) cells at the cerebrovasculature were more frequent in TLE brain tissues as compared to the autoptic control. Conclusions: The rearrangement of PDGFRβ(+) and vascular NG2DsRed cells after SE suggests a possible involvement of pericytes in the cerebrovascular modifications observed in epilepsy. The functional role of vascular-parenchymal PDGFRβ(+) cell redistribution and the relevance of a pericyte response to SE remain to be fully elucidated.