دورية أكاديمية
Suppression of kindling epileptogenesis by adenosine releasing stem cell-derived brain implants.
| العنوان: | Suppression of kindling epileptogenesis by adenosine releasing stem cell-derived brain implants. |
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| المؤلفون: | Tianfu Li, Julius A. Steinbeck, Theresa Lusardi, Philipp Koch, Jing Q. Lan, Andrew Wilz, Michaela Segschneider, Roger P. Simon, Oliver Brüstle, Detlev Boison |
| المصدر: | Brain: A Journal of Neurology; May2007, Vol. 130 Issue 5, p1276-1276, 1p |
| مصطلحات موضوعية: | ADENOSINES, CELLS, THERAPEUTICS, EPILEPSY |
| مستخلص: | Epilepsy therapy is largely symptomatic and no effective therapy is available to prevent epileptogenesis. We therefore analysed the potential of stem cell-derived brain implants and of paracrine adenosine release to suppress the progressive development of seizures in the rat kindling-model. Embryonic stem (ES) cells, engineered to release the inhibitory neuromodulator adenosine by biallelic genetic disruption of the adenosine kinase gene (Adk-/-), and respective wild-type (wt) cells, were differentiated into neural precursor cells (NPs) and injected into the hippocampus of rats prior to kindling. Therapeutic effects of NP-derived brain implants were compared with those of wt baby hamster kidney cells (BHK) and adenosine releasing BHK cell implants (BHK-AK2), which were previously shown to suppress seizures by paracrine adenosine release. Wild-type NP-graft recipients were characterized by an initial delay of seizure development, while recipients of adenosine releasing NPs displayed sustained protection from developing generalized seizures. In contrast, recipients of wt BHK cells failed to display any effects on kindling development, while recipients of BHK-AK2 cells were only moderately protected from seizure development. The therapeutic effect of Adk-/--NPs was due to graft-mediated adenosine release, since seizures could transiently be provoked after blocking adenosine A |
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| قاعدة البيانات: | Complementary Index |
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