Focal neocortical epilepsies are caused by a variety of pathological events that include malformations due to abnormal early prenatal cortical development or postnatally acquired cortical dysplasias (CDs). Patients with these lesions often have drug resistant epilepsy and need surgical intervention. Removal of these foci inevitably involves removal of adjacent normal tissue. This tissue is an important resource that can be used to elucidate the mechanism(s) underlying the disorder. Biomedical research has witnessed a huge increase in the amount of DNA sequence information that is now publicly available. Many new technologies are now available which allow global monitoring of many genes as opposed to the study of single genes/proteins. The most powerful are the microarrays which allow simultaneous survey of thousands of genes to determine expression levels in specific tissues.
Our Specific Aims are (1) to use the tissues resected from patients with drug resistant CDs and determine gene expression patterns compared to adjacent normal cortex using oligonucleotide arrays. This will allow a global survey of about 60,000 genes. (2) Once we have identified which genes are consistently changed in the epileptic tissue compared to the normal we will construct a cDNA microarray. This will contain candidate epilepsy genes and can be used to confirm findings as well as extend the number of samples which can be tested to further define the genetic differences in congenital versus perinatally acquired CDs to determine which are pathologically relevant changes. (3) Finally, to study the in situ expression of a selected number of the identified genes using RT PCR technology and their corresponding proteins using immunocytochemical techniques. This is a unique opportunity to screen large numbers of genes that may be involved in epileptogenesis using samples which are electrophysiologically and pathologically well defined.
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