Department of Neurology,Qingdao Municipal Hospital,Taishan Medical University,China；Department of Neurology,Qingdao Central Hospital,China；Department of Neurology,Qingdao Municipal Hospital,School of Medicine,Qingdao University,China；Department of Neurology,Qingdao Municipal Hospital,School of Medicine,Qingdao University,China；College of Medicine and Pharmaceutics,Ocean University of China,Qingdao 266003,China；Department of Neurology,Qingdao Municipal Hospital,Taishan Medical University,China；Department of Neurology,Qingdao Municipal Hospital,School of Medicine,Qingdao University,China；College of Medicine and Pharmaceutics,Ocean University of China,Qingdao 266003,China
Background and purpose:Drug resistance in epilepsy is considered as a complicated and multifactorial problem.Insufficient level of the antiepileptic drugs (AEDs) at the targeted brain region has been discussed as one mechanism contributing to pharmacoresistance of epilepsies.Modulating permeability of the blood-brain barrier (BBB),which facilitates the entry of AEDs into the central nervous system,is the effective treatment strategy.Signaling through receptors for the adenosine is thought to be ...更多
Background and purpose:Drug resistance in epilepsy is considered as a complicated and multifactorial problem.Insufficient level of the antiepileptic drugs (AEDs) at the targeted brain region has been discussed as one mechanism contributing to pharmacoresistance of epilepsies.Modulating permeability of the blood-brain barrier (BBB),which facilitates the entry of AEDs into the central nervous system,is the effective treatment strategy.Signaling through receptors for the adenosine is thought to be a potent modulator of BBB permeability.This paper aimed to investigate the effects of auxiliary application of adenosine receptor (AR) agonist on amygdala-kindled seizures in adult male Wistar rats.Methods:When fully kindled seizures were achieved by daily electrical stimulation of the amygdale,rats were randomly divided into three groups:control,phenytoin (PHT),and PHT+ Aenosine-5'-(N-ethylcarboxamide) (NECA) groups.NECA (0.08mg/kg,i.v.) was applied to the PHT+NECA group after the administration of PHT (75mg/kg,i.p.on the first day;50mg/kg,i.p.on the following 9 days).Results:Intravenous infusion of NECA resulted in a significant increase in brain PHT levels as compared with the PHT treatment alone.On the other hand,the auxiliary application of NECA dramatically decreased the incidence of generalized seizures (GS) and seizure stage,shortened duration of afterdischarge and GS,as well as elevated the afterdischarge threshold (ADT) and GS threshold.Conclusion:Our study demonstrated that auxiliary application of AR agonist enhanced brain antiepileptic drug levels and strengthened the anticonvulsant properties of AED.收起
