Epilepsy Research (2014) 108, 396—404 j ourna l h om epa ge: www.elsevier.com/locate/epilepsyres Glutathione pegylated liposomal methylprednisolone administration after the early phase of status epilepticus did not modify epileptogenesis in the rat Linda Holtman a , Erwin A. van Vliet a,b , Chantal Appeldoorn c , Pieter J. Gaillard c , Marco de Boer c , Rick Dorland c , Wytse J. Wadman a,b , Jan A. Gorter a,b,* a Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Science Park 904, 1098 XH Amsterdam, The Netherlands b Epilepsy Institute in The Netherlands Foundation (Stichting Epilepsie Instellingen Nederland, SEIN), Achterweg 5, 2103 SW Heemstede, The Netherlands c to-BBB technologies BV, J.H. Oortweg 19, 2333 CH Leiden, The Netherlands Received 23 July 2013; received in revised form 2 December 2013; accepted 6 January 2014 Available online 31 January 2014 KEYWORDS Brain inflammation; Temporal lobe epilepsy; Pulse treatment; Methylprednisolone; Liposomes Summary 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 4 h after onset of SE, rats were treated with glutathione pegylated liposomal methylprednisolone (GSH-PEG liposomal MP) according to a treatment protocol (1× per week; 10 mg/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 liposo- mal 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. ∗ Corresponding author at: Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Science Park 904, 1098 XH Amsterdam, The Netherlands. Tel.: +31 205257893. E-mail address: j.a.gorter@uva.nl (J.A. Gorter). 0920-1211/$ — see front matter © 2014 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.eplepsyres.2014.01.010