Pilocarpine-Induced Status Epilepticus in the Rat Hippocampus is Associated with Reactive Glia and Concomitant Increased Expression of CD31, PDGFRβ and Collagen IV in Endothelial Cells and Pericytes of the Blood Brain Barrier

authors

  • Kyriatzis Grigorios
  • Bernard Anne
  • Bôle Angélique
  • Khrestchatisky Michel
  • Ferhat Lotfi

keywords

  • Blood brain barrier
  • Gliosis
  • Temporal lobe epilepsy
  • Inflammation
  • Epileptogenesis
  • Hippocampus
  • Endothelial cells
  • Pericytes
  • Basal membrane blood brain barrier
  • Gliosis
  • Temporal lobe epilepsy
  • Inflammation
  • Epileptogenesis
  • Hippocampus
  • Endothelial cells
  • Pericytes
  • Basal membrane

document type

UNDEFINED

abstract

Temporal lobe epilepsy (TLE) is associated with reorganization of neuronal networks, gliosis, neuroinflammation, loss of integrity of the blood brain barrier (BBB) in the hippocampus in humans and animal models. More than 30% of epilepsies remain intractable and characterization of the molecular mechanisms involved in BBB dysfunction is essential to the identification of new therapeutic strategies. In this work, we induced status epilepticus in rats by injection of the proconvulsant drug pilocarpine that leads to TLE. Using RT-qPCR, double immunohistochemistry and confocal imaging, we studied at different time points of epileptogenesis (latent phase, 3, 7, 14 days; chronic phase, 1 and 3 months) the regulation of reactive glia and vascular markers. In the hippocampus, increased expression of mRNA encoding the glial proteins GFAP and Iba1 confirmed neuroinflammatory status. We report for the first time the concomitant induction in endothelial cells, pericytes and basal membrane of the BBB of specific proteins CD31, PDGFR and ColIV, that peaks at the same time points as inflammation. The altered expression of these proteins occurs early in TLE, during the latent phase, suggesting that they could be associated with early rupture and pathogenicity of the BBB that will contribute to the chronic phase of epilepsy.

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