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.
journal_name
Ann Neuroljournal_title
Annals of neurologyauthors
Bar-Klein G,Klee R,Brandt C,Bankstahl M,Bascuñana P,Töllner K,Dalipaj H,Bankstahl JP,Friedman A,Löscher Wdoi
10.1002/ana.24804subject
Has Abstractpub_date
2016-12-01 00:00:00pages
896-908issue
6eissn
0364-5134issn
1531-8249journal_volume
80pub_type
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journal_title:Annals of neurology
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doi:10.1002/ana.410320302
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abstract::We assessed nigrostriatal dopaminergic function in Parkinson's disease (PD) patients undergoing a double-blind, placebo-controlled surgical trial of embryonic dopamine cell implantation. Forty PD patients underwent positron emission tomography (PET) imaging with [18F]fluorodopa (FDOPA) prior to randomization to transp...
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journal_title:Annals of neurology
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journal_title:Annals of neurology
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journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410100105
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journal_title:Annals of neurology
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doi:10.1002/1531-8249(199902)45:2<255::aid-ana18>3.0.c
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pub_type: 杂志文章
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journal_title:Annals of neurology
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pub_type: 杂志文章
doi:10.1002/ana.410110602
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pub_type: 杂志文章,评审
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更新日期:1994-06-01 00:00:00
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journal_title:Annals of neurology
pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:2004-06-01 00:00:00
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更新日期:2019-03-01 00:00:00
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pub_type: 杂志文章,多中心研究,随机对照试验
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journal_title:Annals of neurology
pub_type: 杂志文章
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更新日期:1984-01-01 00:00:00