Abstracts

Rationale: This study is to further explore the adenosine dysfunction in refractory epilepsy in Sturge Weber Syndrome (SWS), to evaluate the neuronal-level effect of A1R agonist on both excitatory pyramidal neurons and inhibitory interneurons, to discuss the possibility of adenosine augmentation therapy (AAT) using A1R agonist for treating refractory epilepsy in SWS. Methods: The intrinsic excitatory properties of pyramidal cells and fast-spiking interneurons from human brain tissues from SWS cases and malformations of cortical development (MCD) cases were compared using electrophysiology. With application of either A1R agonist or antagonist, the neuronal-level effect of A1R agonist was evaluated in vitro in pyramidal cells and fast-spiking interneurons from SWS cases and MCD cases. Results: No significant difference of intrinsic excitatory properties of pyramidal cells and fast-spiking interneurons was found between SWS cases and MCD cases. In terms of neuronal-level effect of A1R agonist, with 22.88+-1.12% percentage of decreased frequency, fast-spiking interneurons showed relatively highest sensitivity of A1R agonist application, compared with pyramidal cells from SWS cases, fast-spiking interneurons and pyramidal cells from MCD cases. Conclusions: Resection for epileptogenic zone, that is still today first-line treatment for refractory epilepsy in SWS, does help patients with reducing seizures but not reducing life burden, as the decline in motor functions. Our results supported the potential of AAT using A1R agonist to be a novel therapy for reducing life burden from patients with refractory epilepsy in SWS, with application to epileptic generation region but not propagation region. Funding: This study was supported by the Beijing Postdoctoral Research Foundation (2017-122-ZZ) and the National Natural Science Foundation of China (81790654, 81790650).