PMID- 17448638 OWN - NLM STAT- MEDLINE DCOM- 20070703 LR - 20181113 IS - 0920-1211 (Print) IS - 0920-1211 (Linking) VI - 74 IP - 2-3 DP - 2007 May TI - Optical suppression of seizure-like activity with an LED. PG - 201-9 AB - 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. FAU - Rothman, Steven M AU - Rothman SM AD - Department of Neurology, Hope Center, Washington University School of Medicine, St. Louis, MO 63110, United States. rothman@wustl.edu FAU - Perry, Gavin AU - Perry G FAU - Yang, Xiao-Feng AU - Yang XF FAU - Hyrc, Krzysztof AU - Hyrc K FAU - Schmidt, Brigitte F AU - Schmidt BF LA - eng GR - R01 NS42936/NS/NINDS NIH HHS/United States GR - P01 NS032636/NS/NINDS NIH HHS/United States GR - P01 NS NS32636/NS/NINDS NIH HHS/United States GR - R01 NS042936-05/NS/NINDS NIH HHS/United States GR - P01 NS032636-120006/NS/NINDS NIH HHS/United States GR - R01 NS042936/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20070419 PL - Netherlands TA - Epilepsy Res JT - Epilepsy research JID - 8703089 RN - 0 (4-(((2H-1-benzopyran-2-one-7-amino-4-methoxy)carbonyl)amino) butanoic acid) RN - 0 (Anticonvulsants) RN - 0 (GABA Antagonists) RN - 124-87-8 (Picrotoxin) RN - 56-12-2 (gamma-Aminobutyric Acid) RN - SY7Q814VUP (Calcium) SB - IM MH - Animals MH - Anticonvulsants/administration & dosage/*radiation effects/*therapeutic use MH - Calcium/metabolism MH - Cells, Cultured MH - Electrophysiology MH - Epilepsies, Partial/*therapy MH - GABA Antagonists/pharmacology MH - Hippocampus/cytology/drug effects MH - Mice MH - Microscopy, Fluorescence MH - Neurons/drug effects MH - Picrotoxin/pharmacology MH - Seizures/*drug therapy/physiopathology MH - Ultraviolet Rays MH - gamma-Aminobutyric Acid/administration & dosage/*analogs & derivatives/radiation effects/therapeutic use PMC - PMC2074873 MID - NIHMS23755 EDAT- 2007/04/24 09:00 MHDA- 2007/07/04 09:00 PMCR- 2008/05/01 CRDT- 2007/04/24 09:00 PHST- 2007/03/02 00:00 [received] PHST- 2007/03/18 00:00 [accepted] PHST- 2007/04/24 09:00 [pubmed] PHST- 2007/07/04 09:00 [medline] PHST- 2007/04/24 09:00 [entrez] PHST- 2008/05/01 00:00 [pmc-release] AID - S0920-1211(07)00099-X [pii] AID - 10.1016/j.eplepsyres.2007.03.009 [doi] PST - ppublish SO - Epilepsy Res. 2007 May;74(2-3):201-9. doi: 10.1016/j.eplepsyres.2007.03.009. Epub 2007 Apr 19.