Cell swelling, seizures and spreading depression: An impedance study

doi:10.1016/j.neuroscience.2006.02.034

Neuroscience

Volume 140, Issue 2, 2006, Pages 505-515

https://doi.org/10.1016/j.neuroscience.2006.02.034 Get rights and content

Abstract

The cellular processes that take place during the transition from pre-seizure state to seizure remain to be defined. In this study in awake, paralyzed rats, we used an electrical impedance measure of changes in extra-cellular intracranial volume to estimate changes in cell size in acute models of epilepsy. Animals were prepared with extradural electroencephalographic (EEG)/impedance electrodes and a venous catheter. On a subsequent day, animals were paralyzed, ventilated and treated with picrotoxin, kainic acid or fluorocitrate in doses that usually induce epileptiform discharges. We now report that increases in baseline impedance were induced by kainic acid and smaller increases by picrotoxin. We also demonstrated that epileptiform discharges were preceded by small, accelerated increases in impedance. Increases in baseline impedance were highly correlated with increases in power of non-ictal high frequency EEG activity. Seizures were accompanied by increases in impedance and all treatments induced transient, relatively large, increases in impedance often associated with unilateral reductions in low frequency EEG, likely periods of spreading depression. We conclude: cerebral cells swell in convulsant models of epilepsy, that there are pre-ictal accelerations in cell swelling, and that spreading depression-like events are frequently associated with seizures.

Section snippets

Experimental procedures

All studies were approved by the Animal Welfare Committee of Flinders University. Experiments conformed to The Australian Code of Practice for the Care and Use of Animals for Scientific Purposes of the National Health and Medical Research Council. We used as few animals as would provide interpretable results and were careful to minimize suffering.

Normalization of impedance changes

At the conclusion of each study, animals were killed using pentobarbitone which abolished EEG activity and caused a precipitous rise in impedance, initially linear for several minutes, then flattening for a prolonged period which we did not completely record. The inflection point of this curve (mean 17.9±2 ohm above baseline impedance, n=16 animals) was used in each animal to normalize impedance measurements between rats. Results are therefore expressed both as absolute impedance changes and as

Discussion

The novel observations from this study are both surprising and potentially relevant to acute seizure-induction or migraine: first, an increased impedance following convulsants with quite different mechanisms of action and, second, the association of spreading depressions (SDs) with seizures. We also report a small increase in impedance just prior to seizures.

Increases in impedance with agents causing excessive excitation (kainic acid) and insufficient inhibition (picrotoxin) are consistent with

Acknowledgments

Supported by grants from the Swedish Foundation for International Cooperation in Research and Higher Education (STINT). We thank Ms. Jodie Wilson, FMC Biomedical Engineering, for preparation of EEG preamplifiers.

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Citation Excerpt :
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Clinical neuroscienceCell swelling, seizures and spreading depression: An impedance study

Abstract

Section snippets

Experimental procedures

Normalization of impedance changes

Discussion

Acknowledgments

J Neurol Sci

Brain Res

Neurosci Lett

Neuron

Neuroscience

Brain Res Bull

Exp Neurol

Poultry Sci

Epilepsy Res

Neuroimage

Exp Neurol

Brain Res

Neuroscience

Glutamate released from glial cells synchronizes neuronal activity in the hippocampus

J Neurosci

Astroglial cells express large amounts of GABAA receptor proteins in mature brain

J Neurochem

Interstitial space, electrical resistance and ion concentrations during hypotonia of rat hippocampal slices

J Physiol

Cortical slow potential changes during convulsions induced by maximal electroshock or penicillin focus

Metab Brain Dis

Impedance changes during epileptic seizures

Epilepsia

GABAA/benzodiazepine receptors in acutely isolated hippocampal astrocytes

J Neurosci

A mathematical treatment of the electric conductivity and capacity of disperse systems I. The electric conductivity of a suspension of homogeneous spheroids

Physiol Rev

Clinical neuroscience
Cell swelling, seizures and spreading depression: An impedance study