Cerebral Cortex, Vol 8, 623-634, Copyright © 1998 by Oxford University Press
C Redecker, M Lutzenburg, P Gressens, P Evrard, OW Witte and G Hagemann
Malformations of cortical development are increasingly recognized in
association with severe epileptic syndromes, neuropsychological disorders
and mental retardation. Several clinical and experimental studies suggest
that functional consequences of cortical dysplasias are not restricted to
the area of the dysplastic lesion but also involve remote brain regions. In
the present study cortical malformations were induced in newborn rats at
day of birth by intracerebral injection of the glutamatergic agonist
ibotenate. The resulting cytoarchitectonic lesion associates neuronal
depopulation of deep cortical layers, ectopic neurons in superficial layers
and sulcus formation, mimicking human polymicrogyria and migration
disorders. Electrophysiological recordings of evoked field potentials in
slice preparations of adult animals reveal hyperexcitability in widespread
cortical regions surrounding the dysplasia. Low-intensity stimulation
induced epileptiform activity consisting of long-lasting, multiphasic and
N- methyl-D-aspartate-dependent field responses. They appeared with high
variability as all-or-none events. These widespread changes in excitability
were not observed in sham-operated animals with small superficial ectopias
but intact deep cortical layers, indicating that focal loss of these layers
induces extended alterations in cortical connectivity and imbalance of
excitation and inhibition. Restricted zones of increased excitability were
also found in the forelimb and hindlimb representation cortex in
sham-operated and control animals, demonstrating that this activity has to
be considered as an intrinsic property of specific cortical areas.
Deoxyglucose autoradiography showed that the widespread hyperexcitability
in ibotenate-injected animals was not accompanied by alterations in glucose
metabolism, although in the area of structural abnormality a typical
metabolic pattern was found, revealing an increased glucose uptake in layer
I. Hypometabolism as described for many types of human dysplastic lesions
was not observed. This difference between the experimental and clinical
data may be due to the absence of behavioral seizures in this model.
However, it can be hypothesized that in patients with developmental
malformations, additional pathogenic factors contribute to the
manifestation of seizure disorders.
ARTICLES
Excitability changes and glucose metabolism in experimentally induced focal cortical dysplasias
Neurologische Klinik, Heinrich-Heine-Universitat, Dusseldorf, Germany.
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