title: Atorvastatin treatment during epileptogenesis in a rat model for temporal lobe epilepsy.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Science Park 904, Amsterdam, The Netherlands.
authors: Erwin A
authors: EA
authors: van Vliet
authors: Linda
authors: L
authors: Holtman
authors: Eleonora
authors: E
authors: Aronica
authors: Leanne J M
authors: LJ
authors: Schmitz
authors: Wytse J
authors: WJ
authors: Wadman
authors: Jan A
authors: JA
authors: Gorter
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D000069059:Atorvastatin; D001812:Blood-Brain Barrier / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004569:Electroencephalography; D004833:Epilepsy, Temporal Lobe / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D006538:Heptanoic Acids / Q000627:therapeutic use*; D008297:Male; D011758:Pyrroles / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000188:drug therapy / Q000503:physiopathology; D014280:Triglycerides / Q000097:blood
chemical_list: D000927:Anticonvulsants; D006538:Heptanoic Acids; D011758:Pyrroles; D014280:Triglycerides; D000069059:Atorvastatin