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Seizure suppression via glycolysis inhibition with 2‐deoxy‐D‐glucose (2DG)
Author(s) -
Stafstrom Carl E.,
Roopra Avtar,
Sutula Thomas P.
Publication year - 2008
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1167.2008.01848.x
Subject(s) - glycolysis , 2 deoxy d glucose , chemistry , neuroscience , endocrinology , medicine , biology , biochemistry , metabolism
SummaryMetabolic regulation of neuronal excitability is increasingly recognized as a factor in seizure pathogenesis and control. Inhibiting or bypassing glycolysis may be one way through which the ketogenic diet provides an anticonvulsant effect. 2‐deoxy‐D‐glucose (2DG), a nonmetabolizable glucose analog that partially inhibits glycolysis, was tested in several acute and chronic seizure models. Acutely, 2DG decreases the frequency of high‐K + ‐, bicuculline‐ and 4‐aminopyridine‐induced interictal bursts in the CA3 region of hippocampal slices; 2DG also exerts anticonvulsant effects in vivo against perforant path kindling in rats. Chronically, 2DG has novel antiepileptic effects by retarding the progression of kindled seizures. Finally, 2DG has a favorable preliminary toxicity profile. These factors support the possibility that 2DG or other modifiers of glycolysis can be used as novel treatments for epilepsy.