Seizure suppression by adenosine-releasing cells is independent of seizure frequency.
OBJECTIVE
Intraventricular cellular delivery of adenosine was recently shown to be transiently efficient in the suppression of seizure activity in the rat kindling model of epilepsy. We tested whether the suppression of seizures by adenosine-releasing grafts was independent of seizure frequency.


METHODS
Adenosine-releasing cells were encapsulated and grafted into the lateral brain ventricle of rats kindled in the hippocampus. During 4 weeks after grafting, electric test stimulations were delivered at a frequency of either once a week or 3 times per week. Seizure activity was evaluated by visual scoring of seizure severity and by the recording of EEGs.


RESULTS
Adenosine released from encapsulated cells exerted potent antiepileptic activity for >/=2 weeks. One week after grafting, treated rats displayed a complete protection from clonic seizures, and a protection from focal seizures was observed in the majority of animals. Seizure suppression was accompanied by a reduction of afterdischarges in EEG recordings. The protective efficacy of the grafted cells was the same irrespective of whether electrical test stimulations were delivered 1 or 3 times per week. Rats receiving control grafts continued to display full clonic convulsions.


CONCLUSIONS
This study demonstrated that the frequency of test stimulations did not influence the seizure-suppressive potential of adenosine-releasing grafts. Thus the local delivery of adenosine is likely to be effective in seizure control over a threefold range of seizure-discharge frequency.
Boison
Detlev
D
Institute of Pharmacology and Toxicology, University of Zurich, Switzerland. boison@pharma.unizh.ch
Huber
Alexander
A
Padrun
Vivianne
V
Déglon
Nicole
N
Aebischer
Patrick
P
Möhler
Hanns
H
D000241:Adenosine / Q000008:administration & dosage* / Q000378:metabolism / Q000627:therapeutic use; D000818:Animals; D002214:Capsules; D002470:Cell Survival; D017690:Cell Transplantation / Q000379:methods; D002552:Cerebral Ventricles; D006224:Cricetinae; D004569:Electroencephalography; D004827:Epilepsy / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D007668:Kidney / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D007696:Kindling, Neurologic; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D002214:Capsules; D000241:Adenosine