The role of adenosine A1 receptor agonist in adenosine augmentation therapy for patients with refractory epilepsy in Sturge-Weber syndrome: An in vitro electrophysiological study

Epilepsy Behav. 2020 May:106:107034. doi: 10.1016/j.yebeh.2020.107034. Epub 2020 Mar 21.

Abstract

Purposes: This study was to further explore the adenosine dysfunction in refractory epilepsy in Sturge-Weber Syndrome (SWS), to evaluate the neuronal-level effect of the A1 receptor (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.

Materials and methods: The intrinsic excitatory properties of pyramidal cells (PCs) and fast-spiking (FS) interneurons from human brain tissues with 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 PCs and FS interneurons from SWS cases and MCD cases.

Results: No significant difference of passive excitatory properties of PCs and FS interneurons was found between SWS cases and MCD cases. In terms of the neuronal-level effect of A1R agonist, with 22.88 ± 1.12% percentage of decreased frequency, FS interneurons showed relatively highest sensitivity of A1R agonist application, compared with PCs from SWS cases and FS interneurons and PCs from MCD cases.

Conclusion: Our results supported the potential of AATs 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.

Keywords: Adenosine A1 receptor; Adenosine augmentation therapy; Fast-spiking interneuron; Refractory epilepsy; Sturge–Weber syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / administration & dosage*
  • Adenosine A1 Receptor Agonists / administration & dosage*
  • Adenosine A1 Receptor Antagonists / administration & dosage
  • Adolescent
  • Adult
  • Animals
  • Child
  • Child, Preschool
  • Drug Resistant Epilepsy / drug therapy*
  • Drug Resistant Epilepsy / physiopathology
  • Electroencephalography* / methods
  • Electrophysiological Phenomena / physiology
  • Female
  • Humans
  • Infant
  • Interneurons / drug effects*
  • Interneurons / physiology
  • Male
  • Neurons / drug effects
  • Neurons / physiology
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / physiology
  • Sturge-Weber Syndrome / drug therapy*
  • Sturge-Weber Syndrome / physiopathology
  • Young Adult

Substances

  • Adenosine A1 Receptor Agonists
  • Adenosine A1 Receptor Antagonists
  • Adenosine