Abstracts

Neurogenesis has been described in specific areas in the normal human brain. This study was undertaken to investigate whether neurogenesis occurs in epileptogenic areas in patients with intractable epilepsy. We studied 14 patients (mean age: 19.1 years old) with medically intractable epilepsy who underwent epilepsy surgery. During surgical resections, en bloc cortical and subcortical samples were collected and cultured with BrdU (a marker for proliferating cells) for 24, 48 and 72 hours. Cultured slices were later fixed for immunocytochemistry (ICC) and immunofluorescence (for double labeling). The following primary antibodies were used: anti-BrdU, anti-TUJ1, anti- MAP2 and anti-NeuN (for neurons), anti-GFAP (for glial cells), anti-Nestin and anti-CD133 (for stem-cells). Histology revealed MCD in 9 patients: 3 patients with hemimegalencephaly and 6 focal cortical dysplasia. Perinatal infarction (PI) was confirmed in 3 patients and 2 had the diagnosis of gliosis secondary to trauma. Eight patients were analyzed as controls (normal temporal cortex). There was significant BrdU uptake in 5 out of 8 patients with MCD and in all 3 patients with PI, that was mainly located but not restricted to the subventricular zone (SVZ). Positive BrdU cells were found in all abnormal samples resected from frontal, parietal, temporal or occipital lobes. There were no BrdU positive cells seen in any of the 8 [ldquo]control[rdquo] temporal lobe samples. Intense BrDU uptake was found in SVZ with progressive decrement in its expression toward cortical surface in samples that were cultured for 24 hours. In samples that were cultured for 48 and 72 hours, a more diffuse BrdU immunoreactivity was observed with presence of an increased number of BrdU stained cells in white matter (intermediate zone). Nestin and BrdU co-localization was found in the SVZ cells only. BrdU and Tuj1 co-localization was observed in the entire length of the cortical mantle. No co-localization was observed between BrdU and GFAP. Our results suggest the presence of replication, migration and preferential differentiation of stem cells into neurons in neocortical epilepsy. Our study shows a clear trend toward early neuronal differentiation in the epileptic and histologically abnormal samples. The role and function of these cells in neocortical epilepsies remain unknown. (Supported by NINDS grant for Imad M Najm (K08NS02046 and 1R21 NS42354))