Differential effects of low glucose concentrations on seizures and epileptiform activity in vivo and in vitro.
In vivo, severe hypoglycemia is frequently associated with seizures. The hippocampus is a structure prone to develop seizures and seizure-induced damage. Patients with repeated hypoglycemic episodes have frequent memory problems, suggesting impaired hippocampal function. Here we studied the effects of moderate hypoglycemia on primarily generalized flurothyl-induced seizures in vivo and, using EEG recordings, we determined involvement of the hippocampus in hypoglycemic seizures. Moderate systemic hypoglycemia had proconvulsant effects on flurothyl-induced clonic (forebrain) seizures. During hypoglycemic seizures, seizure discharges were recorded in the hippocampus. Thus, we continued the studies in combined entorhinal cortex-hippocampus slices in vitro. However, in vitro, decreases in extracellular glucose from baseline 10 mM to 2 or 1 mM did not induce any epileptiform discharges. In fact, low glucose (2 and 1 mM) attenuated preexisting low-Mg2+-induced epileptiform activity in the entorhinal cortex and hippocampal CA1 region. Osmolarity compensation in low-glucose solution using mannitol impaired slice recovery. Additionally, using paired-pulse stimuli we determined that there was no impairment of GABAA inhibition in the dentate gyrus during glucopenia. The data strongly indicate that, although forebrain susceptibility to seizures is increased during moderate in vivo hypoglycemia and the hippocampus is involved during hypoglycemic seizures, glucose depletion in vitro contributes to an arrest of epileptiform activity in the system of the entorhinal cortex-hippocampus network and there is no impairment of net GABAA inhibition during glucopenia.
Johannes Müller Institut für Physiologie, Universitätsklinikum Charité, Humboldt Universität, Berlin, Germany.
Anne
A
Kirchner
Jana
J
Velísková
Libor
L
Velísek
D000818:Animals; D018728:Entorhinal Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004829:Epilepsy, Generalized / Q000503:physiopathology*; D005947:Glucose / Q000494:pharmacology; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006624:Hippocampus / Q000503:physiopathology; D007003:Hypoglycemia / Q000503:physiopathology*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D008274:Magnesium / Q000502:physiology; D008297:Male; D016548:Prosencephalon / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology; D012640:Seizures / Q000503:physiopathology*
D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D007328:Insulin; D011963:Receptors, GABA-A; D008274:Magnesium; D005947:Glucose