Abstracts

ROLE OF REELIN IN EPILEPTOGENIC CORTICAL MALFORMATIONS IN PEDIATRIC PATIENTS

Abstract number : 3.004
Submission category :
Year : 2005
Submission ID : 5810
Source : www.aesnet.org
Presentation date : 12/3/2005 12:00:00 AM
Published date : Dec 2, 2005, 06:00 AM

Authors :
1Ioulia V. Fomitcheva, 1Mark R. Lee, 2Richard B. Hessler, and 1Sergei A. Kirov

Malformations of Cortical Development (MCD) are increasingly recognized as pathophysiological substrates of human temporal lobe epilepsy ([sim]30% of surgery cases). Reelin is an important regulator of neuronal migration and it is implicated in the etiology of the diseases of abnormal neuronal connectivity. We hypothesize that reelin plays role in cellular abnormalities that manifest as MCD and its function may be linked to the regulation of neuronal networks that are impaired in epileptogenic regions. Parent/guardian informed consent documents and children[apos]s assent documents were obtained from each patient involved in the study. All protocols were approved by Institutional Review Board. Standard immunohistochemical techniques were used to study reelin expression in human cortex. Briefly, samples were fast fixed in 10% formalin and paraffin embedded. 5[mu]M sections were cut, washed and blocked in 5% goat serum. Monoclonal mouse anti-reelin antibody (Chemicon) was used in 1:1000 dilution followed by application of a Cy2-conjugated secondary antibody. Fluorescence images were obtained using a krypton-argon laser with standard excitation line at 488 using Zeiss LSM510 confocal microscope. We performed immunostaining for reelin in cortical samples of patients whose pathological records indicated the occurrence of microdysgenesis (MDG), a cortical abnormality associated with developmental defects in neuronal migration. Significantly enhanced reelin expression was found in MDG-affected cortex compared to control samples. Two distinct types of reelin localization were noted. Patients with evidence of mild to moderate MDG showed high expression of reelin mostly localized to cell bodies. Another type of cellular distribution of reelin was found in cortical neurons of one patient diagnosed with hemimeganencephaly and severe microdysgenesis. Enhanced expression of reelin was localized primarily in dendrites, with less immunostaining in the cell bodies. Hemimeganencephaly is a type of malformation that originates from abnormal cell proliferation, unlike MDG that results from disrupted late stages of neuronal migration. These data are consistent with the hypothesis that relates the differences in the types of cortical abnormalities to the developmental timepoints when the putative disruption occurred (Barkovich et al, 2001). Our data provides evidence that reelin plays an important role in epileptogenic cortical malformations in the pediatric cortex. These results suggest that reelin may serve as a marker of certain types of MCD lesions in epileptic patients. Detection and removal of MCD lesions correlates with good postoperative outcome in patients. Therefore, in MCD-related cases the implementation of routine histopathological evaluation of surgical margins using reelin as a marker may be beneficial for the evaluation of post-surgical prognosis. (Supported by NIMH KO1MH02000 to SAK.)