title: Isoflurane prevents acquired epilepsy in rat models of temporal lobe epilepsy.
abstract: Acquired epilepsy is a devastating long-term risk of various brain insults, including trauma, stroke, infections, and status epilepticus (SE). There is no preventive treatment for patients at risk. Attributable to the complex alterations involved in epileptogenesis, it is likely that multitargeted approaches are required for epilepsy prevention. We report novel preclinical findings with isoflurane, which exerts various nonanesthetic effects that may be relevant for antiepileptogenesis.
  
  
  
  The effects of isoflurane were investigated in two rat models of SE-induced epilepsy: intrahippocampal kainate and systemic administration of paraoxon. Isoflurane was either administered during (kainate) or after (paraoxon) induction of SE. Magnetic resonance imaging was used to assess blood-brain barrier (BBB) dysfunction. Positron emission tomography was used to visualize neuroinflammation. Long-term electrocorticographic recordings were used to monitor spontaneous recurrent seizures. Neuronal damage was assessed histologically.
  
  
  
  In the absence of isoflurane, spontaneous recurrent seizures were common in the majority of rats in both models. When isoflurane was administered during kainate injection, duration and severity of SE were not affected, but only few rats developed spontaneous recurrent seizures. A similar antiepileptogenic effect was found when paraoxon-treated rats were exposed to isoflurane after SE. Moreover, in the latter model, isoflurane prevented BBB dysfunction and neurodegeneration, whereas isoflurane reduced neuroinflammation in the kainate model.
  
  
  
  Given that isoflurane is a widely used volatile anesthetic, and is used for inhalational long-term sedation in critically ill patients at risk to develop epilepsy, our findings hold a promising potential to be successfully translated into the clinic. Ann Neurol 2016;80:896-908.
authors.affiliation: Departments of Physiology and Cell Biology, Cognitive and Brain Sciences, the Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Guy
authors.initials: G
authors.lastname: Bar-Klein
authors.affiliation: Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, Hannover, Germany.|Center for Systems Neuroscience, Hannover, Germany.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Klee
authors.affiliation: Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Brandt
authors.affiliation: Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, Hannover, Germany.|Center for Systems Neuroscience, Hannover, Germany.
authors.forename: Marion
authors.initials: M
authors.lastname: Bankstahl
authors.affiliation: Department of Nuclear Medicine, Hannover Medical School, Germany.
authors.forename: Pablo
authors.initials: P
authors.lastname: Bascuñana
authors.affiliation: Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Töllner
authors.affiliation: Department of Medical Neuroscience, Dalhousie University, Halifax, Canada.
authors.forename: Hotjensa
authors.initials: H
authors.lastname: Dalipaj
authors.affiliation: Department of Nuclear Medicine, Hannover Medical School, Germany.
authors.forename: Jens P
authors.initials: JP
authors.lastname: Bankstahl
authors.affiliation: Departments of Physiology and Cell Biology, Cognitive and Brain Sciences, the Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel.|Department of Medical Neuroscience, Dalhousie University, Halifax, Canada.
authors.forename: Alon
authors.initials: A
authors.lastname: Friedman
authors.affiliation: Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, Hannover, Germany.|Center for Systems Neuroscience, Hannover, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Löscher
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000000981:diagnostic imaging; D004195:Disease Models, Animal; D000069280:Electrocorticography; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D007249:Inflammation / Q000000981:diagnostic imaging / Q000517:prevention & control; D007530:Isoflurane / Q000494:pharmacology*; D007608:Kainic Acid; D008279:Magnetic Resonance Imaging; D008297:Male; D059906:Neuroimaging; D009474:Neurons / Q000473:pathology; D010261:Paraoxon; D049268:Positron-Emission Tomography; D051381:Rats
chemical_list: D007530:Isoflurane; D010261:Paraoxon; D007608:Kainic Acid