Dysmorphic Neurons Show Intrinsic Electrophysiological and Anatomical Abnormalities in Pediatric Cortical Dysplasia Tissue.
Abstract number :
E.02
Submission category :
Year :
2000
Submission ID :
1122
Source :
www.aesnet.org
Presentation date :
12/2/2000 12:00:00 AM
Published date :
Dec 1, 2000, 06:00 AM
Authors :
Gary W Mathern, Carlos Cepeda, Jorge Flores-Hernandez, Gloria J Klapstein, Christopher R Calvert, Es Jokel, Delia Mendoza, Katrin Lalezarzadeh, Michael S Levine, UCLA Medical Ctr, Los Angeles, CA; UCLA, Los Angeles, CA.
Rationale: Cortical dysplasia (CD) is the most common pathology in children undergoing epilepsy surgery. Little is known, however, about the underlying epileptogenic mechanisms in CD tissue. We addressed this question by combining single cell in vitro slice electrophysiology and immunostaining in CD tissue. Methods: In vitro techniques recorded 207 cells from 18 pediatric CD cases (ages 9 weeks to 13.9 years). Tissue sites from most and least epileptogenic regions were sampled based on neuroimaging and ECoG abnormalities. Neurons were visualized by Nomarski optics and infrared (IR) videomicroscopy, and voltage clamp techniques were used. Adjacent tissue blocks were immunostained for neuronal and glial markers along with glutamate and GABA receptor subunits. Results: Abnormal morphologic cells were recorded in 15 (83%) cases. Morphologic abnormalities included large dysmorphic cells (n=21), normal sized bipolar/misshapen cells (n=22), and cells with apical dendrites pointing toward the white matter (n=9). Electrophysiological abnormalities were frequent in dysmorphic cells, and included minimal or no voltage-gated sodium currents, minimal or increased voltage-gated calcium currents, and minimal or no synaptic-mediated response to glutamate agonists. Normal, misshapen, and other mildly abnormal cells displayed increased voltage-gated calcium currents, spontaneous inward cellular currents, hypo- and hyper-synaptic responses to application of NMDA, rhythmic oscillations that were most likely GABA mediated, or normal responses. Staining of adjacent tissue blocks indicated that dysmorphic cells were likely neurons, and showed abnormal cellular localization of glutamate and GABA receptor subunits. Conclusions: Dysmorphic and other abnormal cells within pediatric CD tissue show significant abnormalities in intrinsic electrophysiological properties and immunostaining for glutamate and GABA receptor subunits. These changes may lead to cellular hyper- and/or hypo-excitability in a manner that promotes seizure generation in CD tissue. Supported by NIH grants NS 28383, 38992, and 36536.