title: Glutathione pegylated liposomal methylprednisolone administration after the early phase of status epilepticus did not modify epileptogenesis in the rat.
abstract: It has been reported that glucocorticoids (GCs) can effectively control seizures in pediatric epilepsy syndromes, possibly by inhibition of inflammation. Since inflammation is supposed to be involved in epileptogenesis, we hypothesized that treatment with GCs would reduce brain inflammation and thereby modify epileptogenesis in a rat model for temporal lobe epilepsy, in which epilepsy gradually develops after electrically induced status epilepticus (SE). To prevent the severe adverse effects that are inevitable with long-term GC treatment, we used liposome nanotechnology (G-Technology(®)) to enhance the sustained delivery to the brain. Starting 4h after onset of SE, rats were treated with glutathione pegylated liposomal methylprednisolone (GSH-PEG liposomal MP) according to a treatment protocol (1× per week; 10mg/kg) that is effective in other models of neuroinflammation. Continuous electro-encephalogram (EEG) recordings revealed that SE duration and onset of spontaneous seizures were not affected by GSH-PEG liposomal MP treatment. The number and duration of spontaneous seizures were also not different between vehicle and GSH-PEG liposomal MP-treated animals. Six weeks after SE, brain inflammation, as assessed by quantification of microglia activation, was not reduced by GSH-PEG liposomal MP-treatment. Also, neuronal cell loss and mossy fiber sprouting were not affected. Our study shows that the selected GSH-PEG liposomal MP treatment regimen that was administered beyond the acute SE phase does not reduce brain inflammation and development of temporal lobe epilepsy.
authors.affiliation: Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Science Park 904, 1098 XH Amsterdam, The Netherlands.
authors.forename: Linda
authors.initials: L
authors.lastname: Holtman
authors.affiliation: Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Science Park 904, 1098 XH Amsterdam, The Netherlands; Epilepsy Institute in The Netherlands Foundation (Stichting Epilepsie Instellingen Nederland, SEIN), Achterweg 5, 2103 SW Heemstede, The Netherlands.
authors.forename: Erwin A
authors.initials: EA
authors.lastname: van Vliet
authors.affiliation: to-BBB technologies BV, J.H. Oortweg 19, 2333 CH Leiden, The Netherlands.
authors.forename: Chantal
authors.initials: C
authors.lastname: Appeldoorn
authors.affiliation: to-BBB technologies BV, J.H. Oortweg 19, 2333 CH Leiden, The Netherlands.
authors.forename: Pieter J
authors.initials: PJ
authors.lastname: Gaillard
authors.affiliation: to-BBB technologies BV, J.H. Oortweg 19, 2333 CH Leiden, The Netherlands.
authors.forename: Marco
authors.initials: M
authors.lastname: de Boer
authors.affiliation: to-BBB technologies BV, J.H. Oortweg 19, 2333 CH Leiden, The Netherlands.
authors.forename: Rick
authors.initials: R
authors.lastname: Dorland
authors.affiliation: Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Science Park 904, 1098 XH Amsterdam, The Netherlands; Epilepsy Institute in The Netherlands Foundation (Stichting Epilepsie Instellingen Nederland, SEIN), Achterweg 5, 2103 SW Heemstede, The Netherlands.
authors.forename: Wytse J
authors.initials: WJ
authors.lastname: Wadman
authors.affiliation: Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Science Park 904, 1098 XH Amsterdam, The Netherlands; Epilepsy Institute in The Netherlands Foundation (Stichting Epilepsie Instellingen Nederland, SEIN), Achterweg 5, 2103 SW Heemstede, The Netherlands. Electronic address: j.a.gorter@uva.nl.
authors.forename: Jan A
authors.initials: JA
authors.lastname: Gorter
mesh_terms: D000418:Albumins; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D039481:CD11b Antigen / Q000378:metabolism; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D004567:Electrodes, Implanted / Q000009:adverse effects; D005978:Glutathione / Q000008:administration & dosage*; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage* / Q000097:blood; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D010743:Phospholipids / Q000008:administration & dosage*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000188:drug therapy* / Q000209:etiology; D013997:Time Factors
chemical_list: D000418:Albumins; D000893:Anti-Inflammatory Agents; D039481:CD11b Antigen; D010743:Phospholipids; C050797:liposom; D010751:Phosphopyruvate Hydratase; D005978:Glutathione; D008775:Methylprednisolone
keywords: Brain inflammation; Liposomes; Methylprednisolone; Pulse treatment; Temporal lobe epilepsy