Grafts of adenosine-releasing cells suppress seizures in kindling epilepsy.

Huber A; Padrun V; Deglon NAebischer PMohler HBoison D

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Grafts of adenosine-releasing cells suppress seizures in kindling epilepsy.

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Adenosine is an inhibitor of neuronal activity in the brain. The local release of adenosine from grafted cells was evaluated as an ex vivo gene therapy approach to suppress synchronous discharges and epileptic seizures. Fibroblasts were engineered to release adenosine by inactivating the adenosine-metabolizing enzymes adenosine kinase and adenosine deaminase. After encapsulation into semipermeable polymers, the cells were grafted into the brain ventricles of electrically kindled rats, a model of partial epilepsy. Grafted rats provided a nearly complete protection from behavioral seizures and a near-complete suppression of afterdischarges in electroencephalogram recordings, whereas the full tonic-clonic convulsions in control rats remained unaltered. Thus, the local release of adenosine resulting in adenosine concentrations <25 nM at the site of action is sufficient to suppress seizure activity and, therefore, provides a potential therapeutic principle for the treatment of drug-resistant partial epilepsies.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2001年第13期|7611-7616|共6页
作者
Huber A; Padrun V; Deglon NAebischer PMohler HBoison D;
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作者单位

Institute of Pharmacology and Toxicology, Eidgenossische Technische Hochschule and University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.;

itt.edu;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
Adenosine; Adenosine Deaminase; Adenosine Kinase; Brain; Cell Transplantation; 腺苷; 腺苷脱氨酶; 腺苷激酶; 脑; 细胞移植; 发作;

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Grafts of adenosine-releasing cells suppress seizures in kindling epilepsy.

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