Preprint Article Version 2 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 27 September 2023 / Approved: 28 September 2023 / Online: 29 September 2023 (08:26:25 CEST)
Version 2 : Received: 18 January 2024 / Approved: 18 January 2024 / Online: 18 January 2024 (14:00:33 CET)

A peer-reviewed article of this Preprint also exists.

Kyriatzis, G.; Bernard, A.; Bôle, A.; Khrestchatisky, M.; Ferhat, L. In the Rat Hippocampus, Pilocarpine-Induced Status Epilepticus 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. Int. J. Mol. Sci. 2024, 25, 1693. Kyriatzis, G.; Bernard, A.; Bôle, A.; Khrestchatisky, M.; Ferhat, L. In the Rat Hippocampus, Pilocarpine-Induced Status Epilepticus 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. Int. J. Mol. Sci. 2024, 25, 1693.

Abstract

Temporal lobe epilepsy (TLE) is associated with reorganization of hippocampal neuronal net-works, gliosis, neuroinflammation, loss of integrity of the blood-brain barrier (BBB) 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 thera-peutic strategies. In this work, we induced status epilepticus in rats by injection of the proconvul-sant drug pilocarpine that leads to TLE. Using RT-qPCR, double immunohistochemistry and con-focal 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 hippo-campus, increased expression of mRNA encoding the glial proteins GFAP and Iba1 confirmed neu-roinflammatory status. We report for the first time the concomitant induction in endothelial cells, pericytes and basement 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 ear-ly 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.

Keywords

Temporal lobe epilepsy; Pilocarpine; Hippocampus; Epileptogenesis; Gliosis; Inflammation; Blood-brain barrier; Endothelial cells; Pericytes; Basement membrane

Subject

Biology and Life Sciences, Neuroscience and Neurology

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