EXCITABILITY CHANGES AND GLUCOSE-METABOLISM IN EXPERIMENTALLY-INDUCEDFOCAL CORTICAL DYSPLASIAS

Malformations of cortical development are increasingly recognized in a ssociation with severe epileptic syndromes, neuropsychological disorde rs and mental retardation. Several clinical and experimental studies s uggest that functional consequences of cortical dysplasias are not res tricted to the area of the dysplastic lesion but also involve remote b rain regions. In the present study cortical malformations were induced in newborn rats at day of birth by intracerebral injection of the glu tamatergic agonist ibotenate. The resulting cytoarchitectonic lesion a ssociates neuronal depopulation of deep cortical layers, ectopic neuro ns in superficial layers and sulcus formation, mimicking human polymic rogyria and migration disorders. Electrophysiological recordings of ev oked field potentials in slice preparations of adult animals reveal hy perexcitability in widespread cortical regions surrounding the dysplas ia. 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-op erated animals with small superficial ectopias but intact deep cortica l layers, indicating that focal loss of these layers induces extended alterations in cortical connectivity and imbalance of excitation and i nhibition. Restricted zones of increased excitability were also found in the forelimb and hindlimb representation cortex in sham-operated an d control animals, demonstrating that this activity has to be consider ed as an intrinsic property of specific cortical areas. Deoxyglucose a utoradiography showed that the widespread hyperexcitability in ibotena te-injected animals was not accompanied by alterations in glucose meta bolism, although in the area of structural abnormality a typical metab olic pattern was found, revealing an increased glucose uptake in layer I. Hypometabolism as described for many types of human dysplastic les ions was not observed. This difference between the experimental and cl inical data may be due to the absence of behavioral seizures in this m odel. However, it can be hypothesized that in patients with developmen tal malformations, additional pathogenic factors contribute to the man ifestation of seizure disorders.