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dc.contributor.author
Güttinger, Martin
dc.contributor.author
Padrun, Vivianne
dc.contributor.author
Pralong, William F.
dc.contributor.author
Boison, Detlev
dc.date.accessioned
2023-10-24T06:36:40Z
dc.date.available
2017-06-09T10:28:36Z
dc.date.available
2023-10-24T06:36:40Z
dc.date.issued
2005-05
dc.identifier.issn
0014-4886
dc.identifier.issn
1090-2430
dc.identifier.other
10.1016/j.expneurol.2004.12.012
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/33170
dc.description.abstract
Adenosine is an important inhibitory modulator of brain activity. In a previous ex vivo gene therapy approach, local release of adenosine by encapsulated fibroblasts implanted into the vicinity of an epileptic focus, was sufficient to provide transient protection from seizures (Huber, A., Padrun, V., Deglon, N., Aebischer, P., Mohler, H., Boison, D., 2001. Grafts of adenosine-releasing cells suppress seizures in kindling epilepsy. Proc. Natl. Acad. Sci. U. S. A. 98, 7611-7616). Long-term seizure suppression beyond 2 weeks was precluded by limited life expectancy of the encapsulated fibroblasts. To study the feasibility for long-term seizure suppression by adenosine releasing brain implants, in the present contribution, mouse C2C12 myoblasts were engineered to release adenosine by genetic inactivation of adenosine kinase. After encapsulation, the myoblasts were grafted into the lateral brain ventricles of epileptic rats kindled in the hippocampus. While seizure activity in animals with wild-type implants remained unaltered, 1 week after grafting all rats with adenosine-releasing implants (n = 25) displayed complete protection from convulsive seizures and a corresponding reduction of afterdischarges in EEG-recordings. The duration of seizure suppression was maintained for a period of 3 weeks in 50% of the animals ranging to a maximum of 8 weeks in one animal. During the course of these experiments, adenosine A1 receptors remained responsive to selective agonists and antagonists indicating a lack of desensitization of A1 receptors after local long-term exposure to adenosine. Furthermore, local release of adenosine did not affect locomotor activity, whereas systemic application of the A1 agonist 2-chloro-N6-cyclopentyladenosine caused strong sedation. Thus, the local release of adenosine by cellular implants provides a feasible option for a potential side-effect free approach for the long-term treatment of focal epilepsies.
en_US
dc.language.iso
en
en_US
dc.publisher
Elsevier
en_US
dc.subject
adenosine
en_US
dc.subject
adenosine kinase A(1) receptor
en_US
dc.subject
epilepsy
en_US
dc.subject
kindling
en_US
dc.subject
seizure suppression
en_US
dc.subject
cell therapy
en_US
dc.subject
myoblasts
en_US
dc.subject
cell encapsulation
en_US
dc.subject
sedation
en_US
dc.title
Seizure suppression and lack of adenosine A1 receptor desensitization after focal long-term delivery of adenosine by encapsulated myoblasts
en_US
dc.type
Journal Article
dc.date.published
2005-02-12
ethz.journal.title
Experimental Neurology
ethz.journal.volume
193
en_US
ethz.journal.issue
1
en_US
ethz.journal.abbreviated
Exp Neurol
ethz.pages.start
53
en_US
ethz.pages.end
64
en_US
ethz.identifier.wos
ethz.publication.place
San Diego, CA
en_US
ethz.publication.status
published
en_US
ethz.date.deposited
2017-06-09T10:29:04Z
ethz.source
ECIT
ethz.identifier.importid
imp59364de46a20e29948
ethz.ecitpid
pub:53865
ethz.eth
yes
en_US
ethz.availability
Metadata only
en_US
ethz.rosetta.installDate
2017-07-19T01:33:38Z
ethz.rosetta.lastUpdated
2024-02-03T05:39:54Z
ethz.rosetta.versionExported
true
ethz.COinS
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