Correlation between extracellular glucose and seizure susceptibility in adult rats

Abstract

In adult diabetic patients, periods of hyperglycemia may be associated with exacerbation of focal seizures. Our objective was to determine in the adult rats the correlation between seizure susceptibility and extracellular glucose concentration in two models of seizures. Male rats were injected with two doses of streptozocin (40 mg/kg IP) on 2 consecutive days to induce diabetic hyperglycemia. Controls either received vehicle or were not injected. After 2 weeks, blood glucose concentration was measured, and the rats were subjected to flurothyl seizure test. Another group of rats received glucose solution (20%, 5 ml IP) 30 minutes before testing to induce nondiabetic hyperglycemia. Thresholds for flurothyl-induced clonic and tonic-clonic seizures were determined. Finally, in vitro epileptiform activity was induced in the entorhinal cortex-hippocampal slices from naive rats by perfusing with magnesium-free medium with various glucose concentrations. In additional slices, paired-pulse paradigm was determined in the perforant path. Susceptibility to clonic and tonic-clonic flurothyl-induced seizures positively correlated with blood glucose concentrations as the increased glucose concentration was associated with proconvulsant effects. Similarly, in the in vitro experiments, epileptiform activity was promoted by increased and suppressed by decreased glucose concentrations. Data indicate that, in the adult rats, high glucose concentrations are associated with proconvulsant effects.

Risk of epilepsy in type 1 diabetes mellitus: a population-based cohort study

“…Researchers have proposed several hypotheses on the possible pathophysiology of their comorbidity, including immune abnormalities, brain lesions, genetic factors and metabolic abnormalities [23]. In particular, both hyperglycaemia and hypoglycaemia commonly occur in elderly people with diabetes, and can alter the balance between the inhibition and excitation of neuronal networks and cause focal motor seizures [24][25][26]. In addition, we found that younger age was associated with an increased risk of developing epilepsy.…”

Regional neural activity within the substantia nigra during peri-ictal flurothyl generalized seizure stages

“…Plasma glucose measurements-Seizures are accompanied by a significant increase in plasma glucose levels (Handforth and Treiman, 1995b;Schwechter et al, 2003). What can appear as decreased metabolism postictally may be largely the competitive effects of high plasma glucose on 2 DG uptake.…”

“…Glucose level measurements were taken prior to a seizure, immediately following the seizure and 20 min after seizure induction. Blood samples were obtained from tip of the tail (∼10 μl) as described previously (Schwechter et al, 2003). The baseline value for all groups was 46 ± 4 mg/100 ml (mean ± SEM), which is relatively low because the animals did not receive food for up to 20 h before the experiment.…”

The Potential Role of ATP-sensitive Potassium Channels in Treating Epileptic Disorders

“…However, the effects of hyperglycemia on the central nervous system (CNS) and neuronal excitability (Biessel et al, 1994;Stewart et al, 1999;Gispen and Biessel, 2000) are not fully understood. High glucose concentrations have been associated with a lower seizure threshold in an animal model with a single seizure (Schwechter et al, 2003) and neuronal excitability and seizures are related to rapid glucose utilization and glycolysis (Greene et al, 2003). Experimentally, the correlation between extracellular glucose concentration and excitability www.intechopen.com…”

“…The pathophysiology of epileptic seizures in DH is probably multi-factorial. Glucose itself could enhance synaptic transmission and propagation, leading to more excitable neurons (Tutka et al, 1998;Gispen and Biessels, 2000) and even epileptic seizures (Schwechter et al, 2003), regardless of the presence of organic lesions. Underlying focal ischemia has also been suggested as having a role in triggering these partial seizures (Singh and Strobos, 1989).…”