1. Isoflurane prevents acquired epilepsy in rat models of temporal lobe epilepsy
- Author
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Guy Bar-Klein, Hotjensa Dalipaj, Jens P. Bankstahl, Wolfgang Löscher, Alon Friedman, Pablo Bascuñana, Rebecca Klee, Marion Bankstahl, Claudia Brandt, and Kathrin Töllner
- Subjects
0301 basic medicine ,Kainic acid ,medicine.diagnostic_test ,business.industry ,Kainate receptor ,Status epilepticus ,medicine.disease ,Epileptogenesis ,03 medical and health sciences ,chemistry.chemical_compound ,Epilepsy ,030104 developmental biology ,0302 clinical medicine ,Neurology ,chemistry ,Isoflurane ,Anesthesia ,medicine ,Neurology (clinical) ,medicine.symptom ,business ,Electrocorticography ,030217 neurology & neurosurgery ,Neuroinflammation ,medicine.drug - Abstract
Objective 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. Methods 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. Results 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. Interpretation 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
- Published
- 2016
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