Optical suppression of seizure-like activity with an LED.
The therapy of focal epilepsy remains unsatisfactory for as many as 25% of patients. We tested the hypothesis that an efficient, ultraviolet light emitting diode (UV LED), coupled with a newly developed "caged" gamma-aminobutyric acid (GABA), might be capable of terminating "ictal-like" events in cultured murine neurons. GABA was released from BC204, a recently described caged GABA, using a small, ultraviolet (UV) LED. Ictal-like events were provoked by removal of extracellular magnesium. In preliminary control experiments, the concentration of GABA released from our caged compound was dependent upon the strength and duration of the illumination, and readily achieved micromolar (microM) levels that are known to activate tonic, extrasynaptic GABA(A) receptors. Ultraviolet illumination had no effect when BC204 was not present in the perfusate and the currents produced by BC204 were eliminated by picrotoxin. Within a few seconds of UV illumination, BC204 rapidly terminated ictal-like events at low microM concentration. Uncaging of BC204 also blocked the elevation of intracellular calcium induced by seizure-like discharges in our cultures. While much more technical development is clearly required to extend our observations to a more intact preparation, these results suggest the intriguing possibility of constructing an implantable device to "optically suppress" focal human seizures under closed loop control.
Rothman
Steven M
SM
Department of Neurology, Hope Center, Washington University School of Medicine, St. Louis, MO 63110, United States. rothman@wustl.edu <rothman@wustl.edu>
Perry
Gavin
G
Yang
Xiao-Feng
XF
Hyrc
Krzysztof
K
Schmidt
Brigitte F
BF
D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000528:radiation effects* / Q000627:therapeutic use*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004594:Electrophysiology; D004828:Epilepsies, Partial / Q000628:therapy*; D018756:GABA Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000187:drug effects; D010852:Picrotoxin / Q000494:pharmacology; D012640:Seizures / Q000188:drug therapy* / Q000503:physiopathology; D014466:Ultraviolet Rays; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000528:radiation effects / Q000627:therapeutic use
D000927:Anticonvulsants; D002118:Calcium; D018756:GABA Antagonists; D010852:Picrotoxin; D005680:gamma-Aminobutyric Acid; C504213:4-(((2H-1-benzopyran-2-one-7-amino-4-methoxy)carbonyl)amino) butanoic acid