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Hyperthermic spreading depressions in the immature rat hippocampal slice
1Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona 85013-4496, USA.
Insights
Febrile seizures in children may be linked to brain electrical disruptions called hyperthermic spreading depressions (SDs). This study found that rapid temperature increases trigger these SDs, potentially explaining seizure origins.
Area of Science:
- Neuroscience
- Epilepsy Research
- Ionic Homeostasis
Background:
- Febrile seizures are common in young children, but their underlying causes remain unclear.
- Genetic studies suggest channelopathies play a role, but a comprehensive understanding is lacking.
Purpose of the Study:
- To investigate the hypothesis that disrupted ionic homeostasis contributes to febrile seizure development.
- To explore the role of hyperthermia-induced spreading depressions (SDs) in seizure genesis.
Main Methods:
- Electrophysiological experiments were conducted on in vitro rat hippocampal slices.
- Temperature was increased from 34°C to 40°C to induce hyperthermic SDs.
- Neuronal activity, membrane potential, and extracellular ion concentrations were monitored.
Main Results:
- Temperature increases triggered age-dependent hyperthermic SDs, typically around 38.8°C.
- These SDs caused reversible loss of synaptic potentials, decreased input resistance, and epileptiform bursting.
- Significant neuronal depolarization, extracellular field shifts, and increased extracellular K+ were observed during SDs.
Conclusions:
- Hyperthermia-induced spreading depressions are a potential contributing factor to febrile seizures.
- Disordered regulation of ionic homeostasis during hyperthermia may underlie seizure activity.
- Further investigation into hyperthermia-SDs is warranted for understanding febrile seizures.
Abstract:
Febrile seizures are the most common seizure type in children (6 mo to 5 yr). The pathophysiology of febrile seizures is unknown. Current genetic studies show that some febrile seizures result from channelopathies. We have performed electrophysiological experiments in in vitro hippocampal slices to test a novel hypothesis that a disordered regulation of ionic homeostasis underlies the genesis of febrile seizures. In transverse hippocampal CA1 slices from 104 rats, temperature increase from 34 degrees to 40 degrees C produced a series of spreading depressions (SDs), called hyperthermic SDs. The hyperthermic SDs were age-dependent, occurring in only 1/17 8-16 day-old animals, 44/49 17-60 day-old animals, and 11/20 rats older than than 60 days. The hyperthermic SDs usually occurred on the rising phase of the temperature. The mean temperature to trigger a first hyperthermic SD was 38.8 +/- 1.3 degrees C (mean +/- SD, n = 44). The hyperthermic SDs induced a reversible loss of evoked synaptic potentials and a dramatic decrease of input resistance. Neuronal and field epileptiform bursting occurred in the early phases of the hyperthermic SD. During hyperthermic SDs, pyramidal cell membrane potential depolarized by 38.3 +/- 4.9 mV (n = 20), extracellular field shifted negative 18.5 +/- 3.9 mV (n = 44), and extracellular K(+) rose reversibly to 43.8 +/- 10.9 mM (n = 6). Similar SDs could be evoked by ouabain or transient hypoxia with normal temperature. Tetrodotoxin could block initial epileptiform bursting, without blocking SDs. Hyperthermia-induced SDs should be investigated as possible contributing factors to febrile seizures.