期刊
MOLECULAR NEUROBIOLOGY
卷 56, 期 3, 页码 1825-1840出版社
SPRINGER
DOI: 10.1007/s12035-018-1181-y
关键词
Disease-modifying therapy; Temporal lobe epilepsy; Epileptogenesis; Experimental epilepsy models; Video-EEG
资金
- Else-Kroner Fresenius Stiftung
- Novartis Pharma
- Deutsche Forschungsgemeinschaft [SFB 1089, FOR 2715]
- European Union [602102]
- Bundesministerium fur Bildung und Forschung [01GQ0806]
- Bundesministerium fur Bildung und Forschung (EraNet DeCipher)
- Fritz Thyssen Stiftung [11.15.2.022MN]
- BONFOR program of the University of Bonn Medical Center
- EPICARE grant by Associazione Paolo Zorzi per le Neuroscienze and Ricerca Corrente
- Italian ministry of Health [RF151]
- Ricerca Corrente
Temporal lobe epilepsy (TLE) represents a devastating neurological condition, in which approximately 4/5 of patients remain refractory for anti-convulsive drugs. Epilepsy surgery biopsies often reveal the damage pattern of hippocampal sclerosis (HS) characterized not only by neuronal loss but also pronounced astrogliosis and inflammatory changes. Since TLE shares distinct pathogenetic aspects with multiple sclerosis (MS), we have here scrutinized therapeutic effects in experimental TLE of the immunmodulator fingolimod, which is established in MS therapy. Fingolimod targets sphingosine-phosphate receptors (S1PRs). mRNAs of fingolimod target S1PRs were augmented in two experimental post status epilepticus (SE) TLE mouse models (suprahippocampal kainate/pilocarpine). SE frequently induces chronic recurrent seizures after an extended latency referred to as epileptogenesis. Transient fingolimod treatment of mice during epileptogenesis after suprahippocampal kainate-induced SE revealed substantial reduction of chronic seizure activity despite lacking acute attenuation of SE itself. Intriguingly, fingolimod exerted robust anti-convulsive activity in kainate-induced SE mice treated in the chronic TLE stage and had neuroprotective and anti-gliotic effects and reduced cytotoxic T cell infiltrates. Finally, the expression profile of fingolimod target-S1PRs in human hippocampal biopsy tissue of pharmacoresistant TLE patients undergoing epilepsy surgery for seizure relief suggests repurposing of fingolimod as novel therapeutic perspective in focal epilepsies.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据