Abstract:
PURPOSE:Absence epilepsies are common, with a major genetic contribution to etiology. Certain environmental factors can influence absence occurrence but a complete understanding of absence precipitation is lacking. Herein we investigate if lowering blood glucose increases spike-wave activity in mouse models with varying seizure susceptibility. METHODS:Three mouse models were used: an absence seizure model based on the knockin of a human GABA(A) γ2(R43Q) mutation (DBA(R43Q)), the spike-wave discharge (SWD)-prone DBA/2J strain, and the seizure resistant C57Bl/6 strain. Electrocorticography (ECoG) studies were recorded to determine SWDs during hypoglycemia induced by insulin or overnight fasting. KEY FINDINGS:An insulin-mediated reduction in blood glucose levels to 4 mm (c.a. 40% reduction) was sufficient to double SWD occurrence in the DBA(R43Q) model and in the SWD-prone DBA/2J mouse strain. Larger reductions in blood glucose further increased SWDs in both these models. However, even with large reductions in blood glucose, no discharges were observed in the seizure-resistant C57Bl/6 mouse strain. Injection of glucose reversed the impact of insulin on SWDs in the DBA(R43Q) model, supporting a reduction in blood glucose as the modulating influence. Overnight fasting reduced blood glucose levels to 4.5 mm (c.a. 35% reduction) and, like insulin, caused a doubling in occurrence of SWDs. SIGNIFICANCE:Low blood glucose can precipitate SWDs in genetically predisposed animal models and should be considered as a potential environmental risk factor in patients with absence epilepsy.
journal_name
Epilepsiajournal_title
Epilepsiaauthors
Reid CA,Kim TH,Berkovic SF,Petrou Sdoi
10.1111/j.1528-1167.2010.02911.xsubject
Has Abstractpub_date
2011-01-01 00:00:00pages
115-20issue
1eissn
0013-9580issn
1528-1167journal_volume
52pub_type
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