- Atorvastatin treatment during epileptogenesis in a rat model for temporal lobe epilepsy
- Volume | Issue number
- 52 | 7
- Pages (from-to)
- Document type
- Faculty of Science (FNWI)
Faculty of Medicine (AMC-UvA)
- Swammerdam Institute for Life Sciences (SILS)
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.
- go to publisher's site
If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library, or send a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible.