Abstracts

RATIONALE: At the end of this activity the participants will understand abnormalities of neuronal morphology in an animal model of cortical dysgenesis and how they compare to those seen in human acquired cortical dysplasia.
Cortical dysgenesis is a major pathological substrate for intractable epilepsy but the etiology of the majority of these cases is unknown. In utero and perinatal insults can produce [dsquote]acquired[dsquote] cortical dysplasia in humans (Marin-Padilla, 1999). Abnormalities of neuronal morphology are a key feature of many cases of cortical dysplasia in humans and the concept of a [dsquote]dysplastic neuron[dsquote] has received much attention. In utero irradiation was used to produce dysplastic (DC) and heterotopic cortex (HC) in rats. We then used the Golgi-Cox method to study abnormalities of cortical structure and neuronal morphology in DC and HC. These changes were compared control rats and to findings from a collection of specimens of acquired cortical dysplasia in children. This is the first study to directly compare abnormalities of neuronal morphology in an animal model of cortical dysgenesis with a defined clinical pathological entity.
METHODS: Pregnant rats were exposed to 225 cGy [gamma]-irradiation on E17. Offspring were sacrificed for histological testing at 7-8 weeks of age. Brains from 8 irradiated and 5 control rats were processed for histological analysis using the Golgi-Cox method and cut into 200 [mu]-thick sections. Specimens were also compared to a pre-existing collection of Golgi-stained sections from 36 children with acquired cortical dysplasia (Marin-Padilla, 1999). Analysis was carried out using visual examination with light microscopy and camera lucida drawings.
RESULTS: Irradiated animals routinely showed both DC and HC. Both DC and HC contained pyramidal neurons with loss of normal spatial orientation. DC also contained clusters of ectopic neurons near the pia. Frank abnormalities of morphology were present in pyramidal neurons in DC in the form of increased size and long and irregular dendritic branches compared to control neocortex. Similarly, some non-pyramidal (presumed inhibitory) neurons in DC were also abnormally large with longer dendrites compared to control neocortex. Neuronomegaly of this type is also seen in children with acquired cortical dysplasia.
CONCLUSIONS: In utero irradiation produces extensive structural disorganization of the neocortex. Sub-populations of neurons within DC and HC show neuronomegaly and abnormalities in the dendritic arbor. Therefore, an injury-based model of cortical dysgenesis contains neurons that possess some properties that have been described in [dsquote]dysplastic neurons[dsquote]. These abnormalities are also seen in human acquired cortical dysplasia. Some of these morphological changes may be a compensatory response to loss of neighboring cells (hypertrophy of survivors) and abnormalities of afferent fiber distribution (dendritic arbor changes).
[Supported by: This work was supported by a grant from NINDS (NS35651).]