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. Methods NG2DsRed mice were used to visualize cerebrovascular pericytes. The pattern of vascular and parenchymal distribution 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. 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+ cells distribution 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 suggest 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.

P450 metabolic enzymes are expressed in the human and rodent brain. Recent data support their involvement in the pathophysiology of epilepsy. However, the determinants of metabolic enzyme expression in the epileptic brain are unclear. We tested the hypothesis that status epilepticus or exposure to phenytoin or phenobarbital affects brain expression of the metabolic enzyme CYP2E1. Status epilepticus (SE) was induced in C57BL/6J mice by systemic kainic acid. Brain CYP2E1 expression was evaluated 18–24 hours after SE by immunohistochemistry. Co-localization with NEUN, GFAP and CD31 was determined by confocal microscopy. The effect of phenytoin, carbamazepine and phenobarbital on CYP2E1 expression was evaluated in vivo or by using organotypic hippocampal cultures in vitro. CYP2E1 expression was investigated in brain resections from a cohort of drug resistant epileptic brain resections and human endothelial cultures (EPI-EC). Immunohistochemistry showed an increase of CYP2E1 expression limited to hippocampal CA2/3 and hilar neurons after severe SE in mice. CYP2E1 expression was also observed at the astrocyte-vascular interface. Analysis of human brain specimens revealed CYP2E1 expression in neurons and vascular endothelial cells (EC). CYP2E1 was expressed in cultured human EC and over-expressed by EPI-EC. When analyzing the effect of drug exposure on CYP2E1 expression we found that, in vivo or in vitro, ethanol increased CYP2E1 levels in the brain and liver. Treatment with phenytoin induced localized CYP2E1 expression in the brain whereas no significant effects were exerted by carbamazepine or phenobarbital. Our data indicate that the effect of acute SE on brain CYP2E1 expression is localized and cell specific. Exposure to selected anti-epileptic drugs could play a role in determining CYP2E1 brain expression. Additional investigation is required to fully reproduce the culprits of P450 enzyme expression as observed in the human epileptic brain.