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Author
E.A. van Vliet
L. Holtman
E. Aronica
L.J.M. Schmitz
W.J. Wadman
J.A. Gorter
Year
2011
Title
Atorvastatin treatment during epileptogenesis in a rat model for temporal lobe epilepsy
Journal
Epilepsia
Volume | Issue number
52 | 7
Pages (from-to)
1319-1330
Document type
Article
Faculty
Faculty of Science (FNWI)
Faculty of Medicine (AMC-UvA)
Institute
Swammerdam Institute for Life Sciences (SILS)
Abstract
Purpose: It has been shown that blood-brain barrier leakage together with inflammation could contribute to epileptogenesis and seizure progression in a rat model for temporal lobe epilepsy. Because statins have been shown to reduce blood-brain barrier permeability and inflammation in neurological diseases, we aimed to restore the integrity of the blood-brain barrier in epileptic rats using atorvastatin. If this drug could restore the blood-brain barrier, a reduction of brain inflammation might be expected, thereby delaying or preventing the development of epilepsy.
Methods: Rats were orally treated with atorvastatin (once daily, 10 mg/kg) or vehicle for 14 days, starting 7 days before the induction of epilepsy (which was evoked by electrical stimulation of the angular bundle until rats developed status epilepticus). Seizure activity was monitored continuously until 6 weeks after status epilepticus using video-EEG (electroencephalography). Fluorescein was administered at this time point to quantify blood-brain barrier leakage. Brain inflammation, neuronal death, and synaptic reorganization were assessed by (immuno)histologic stainings.
Key Findings: Atorvastatin treatment did not affect the duration of status epilepticus or the development of epilepsy. At 6 weeks after status epilepticus, blood-brain barrier leakage was evident both in atorvastatin-treated and vehicle-treated rats in limbic brain regions (hippocampus, entorhinal cortex, piriform cortex). Atorvastatin treatment had not reduced inflammation, neuronal death, or synaptic reorganization.
Significance: The lack of any favorable effect of atorvastatin on the restoration of the blood-brain barrier, cell death, or brain inflammation suggests that atorvastatin is more effective in neurological diseases where the adaptive immune response plays a crucial role and less so in a disease as temporal lobe epilepsy, where the innate immune response is more prominent.
URL
go to publisher's site
Language
English
Permalink
http://hdl.handle.net/11245/1.348157

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