title: Seizure suppression in kindled rats by intraventricular grafting of an adenosine releasing synthetic polymer.
abstract: Adenosine, an endogenous inhibitory neuromodulator in the central nervous system, exerts anticonvulsant activity that is largely based on the inhibition of the release of excitatory amino acids. As a novel approach to treat pharmacoresistant partial epilepsies, the grafting of adenosine-releasing cells is foreseen to provide a local and sustained source of adenosine. The feasibility of this cell-based therapy was investigated in the present study by the intraventricular implantation of synthetic polymers that release adenosine. Kindled rats with a ventricular implant of an adenosine-releasing polymer showed a profound reduction of seizure activity. This was demonstrated not only by a 75% reduction of grade 5 seizures but also by a reduction of the amplitude and duration of afterdischarges in electroencephalographic (EEG) recordings. Kindled control rats that were implanted with bovine serum albumin (BSA)-containing polymers or were sham operated, continued to show their presurgery seizure pattern. Adenosine displayed antiepileptic activity when released in an amount of 20-50 ng per day. This finding sets the target for the required amount of adenosine to be released from future adenosine-releasing cells for antiepileptic therapy. The present results clearly support the feasibility of a novel therapy for epilepsy based on adenosine-releasing cells.
authors.affiliation: Institute of Pharmacology, ETH, Zurich, Switzerland.
authors.forename: D
authors.initials: D
authors.lastname: Boison
authors.forename: L
authors.initials: L
authors.lastname: Scheurer
authors.forename: J L
authors.initials: JL
authors.lastname: Tseng
authors.forename: P
authors.initials: P
authors.lastname: Aebischer
authors.forename: H
authors.initials: H
authors.lastname: Mohler
mesh_terms: D000241:Adenosine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001672:Biocompatible Materials; D002417:Cattle; D002552:Cerebral Ventricles; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004343:Drug Implants; D004569:Electroencephalography / Q000187:drug effects; D004833:Epilepsy, Temporal Lobe; D005240:Feasibility Studies; D007696:Kindling, Neurologic / Q000187:drug effects*; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011145:Polyvinyls; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000517:prevention & control*; D012710:Serum Albumin, Bovine
chemical_list: D000927:Anticonvulsants; D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D004343:Drug Implants; D018696:Neuroprotective Agents; D011145:Polyvinyls; C016438:ethylenevinylacetate copolymer; D012710:Serum Albumin, Bovine; D000241:Adenosine