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
In humans and animal models, temporal lobe epilepsy (TLE) is associated with reorganization of hippocampal neuronal networks, gliosis, neuroinflammation, and loss of integrity of the blood–brain barrier (BBB). More than 30% of epilepsies remain intractable, and characterization of the molecular mech...
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MDPI AG
2024-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/3/1693 |
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| author | Grigorios Kyriatzis Anne Bernard Angélique Bôle Michel Khrestchatisky Lotfi Ferhat |
| author_facet | Grigorios Kyriatzis Anne Bernard Angélique Bôle Michel Khrestchatisky Lotfi Ferhat |
| author_sort | Grigorios Kyriatzis |
| collection | DOAJ |
| description | In humans and animal models, temporal lobe epilepsy (TLE) is associated with reorganization of hippocampal neuronal networks, gliosis, neuroinflammation, and loss of integrity of the blood–brain barrier (BBB). 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 through injection of the proconvulsant drug pilocarpine, which leads to TLE. Using RT-qPCR, double immunohistochemistry, and confocal imaging, we studied the regulation of reactive glia and vascular markers at different time points of epileptogenesis (latent phase—3, 7, and 14 days; chronic phase—1 and 3 months). 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 of the specific proteins CD31, PDGFRβ, and ColIV—which peak at the same time points as inflammation—in the endothelial cells, pericytes, and basement membrane of the BBB. The altered expression of these proteins occurs early in TLE, during the latent phase, suggesting that they could be associated with the early rupture and pathogenicity of the BBB that will contribute to the chronic phase of epilepsy. |
| first_indexed | 2024-03-08T03:55:36Z |
| format | Article |
| id | doaj.art-60eaa8f8f42f4479a46cee941bdf6f38 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T03:55:36Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-60eaa8f8f42f4479a46cee941bdf6f382024-02-09T15:14:13ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-01-01253169310.3390/ijms25031693In 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 BarrierGrigorios Kyriatzis0Anne Bernard1Angélique Bôle2Michel Khrestchatisky3Lotfi Ferhat4Aix-Marseille Univ, CNRS, INP, Inst Neurophysiopathol, Marseille, France, Institut de Neurophysiopathologie, Faculté de Médecine, 27 Bd Jean Moulin, 13005 Marseille, FranceAix-Marseille Univ, CNRS, INP, Inst Neurophysiopathol, Marseille, France, Institut de Neurophysiopathologie, Faculté de Médecine, 27 Bd Jean Moulin, 13005 Marseille, FranceAix-Marseille Univ, CNRS, INP, Inst Neurophysiopathol, Marseille, France, Institut de Neurophysiopathologie, Faculté de Médecine, 27 Bd Jean Moulin, 13005 Marseille, FranceAix-Marseille Univ, CNRS, INP, Inst Neurophysiopathol, Marseille, France, Institut de Neurophysiopathologie, Faculté de Médecine, 27 Bd Jean Moulin, 13005 Marseille, FranceAix-Marseille Univ, CNRS, INP, Inst Neurophysiopathol, Marseille, France, Institut de Neurophysiopathologie, Faculté de Médecine, 27 Bd Jean Moulin, 13005 Marseille, FranceIn humans and animal models, temporal lobe epilepsy (TLE) is associated with reorganization of hippocampal neuronal networks, gliosis, neuroinflammation, and loss of integrity of the blood–brain barrier (BBB). 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 through injection of the proconvulsant drug pilocarpine, which leads to TLE. Using RT-qPCR, double immunohistochemistry, and confocal imaging, we studied the regulation of reactive glia and vascular markers at different time points of epileptogenesis (latent phase—3, 7, and 14 days; chronic phase—1 and 3 months). 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 of the specific proteins CD31, PDGFRβ, and ColIV—which peak at the same time points as inflammation—in the endothelial cells, pericytes, and basement membrane of the BBB. The altered expression of these proteins occurs early in TLE, during the latent phase, suggesting that they could be associated with the early rupture and pathogenicity of the BBB that will contribute to the chronic phase of epilepsy.https://www.mdpi.com/1422-0067/25/3/1693temporal lobe epilepsypilocarpinehippocampusepileptogenesisgliosisinflammation |
| spellingShingle | Grigorios Kyriatzis Anne Bernard Angélique Bôle Michel Khrestchatisky Lotfi Ferhat 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 International Journal of Molecular Sciences temporal lobe epilepsy pilocarpine hippocampus epileptogenesis gliosis inflammation |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | temporal lobe epilepsy pilocarpine hippocampus epileptogenesis gliosis inflammation |
| url | https://www.mdpi.com/1422-0067/25/3/1693 |
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