Epileptogenicity Correlated with Increased N-Methyl-d-Aspartate Receptor Subunit NR2A/B in Human Focal Cortical Dysplasia
Version of Record online: 2 AUG 2005
Volume 41, Issue 8, pages 971–976, August 2000
How to Cite
Najm, I. M., Ying, Z., Babb, T., Mohamed, A., Hadam, J., LaPresto, E., Wyllie, E., Kotagal, P., Bingaman, W., Foldvary, N., Morris, H. and Lüders, H. O. (2000), Epileptogenicity Correlated with Increased N-Methyl-d-Aspartate Receptor Subunit NR2A/B in Human Focal Cortical Dysplasia. Epilepsia, 41: 971–976. doi: 10.1111/j.1528-1157.2000.tb00281.x
- Issue online: 2 AUG 2005
- Version of Record online: 2 AUG 2005
- Accepted May 24, 2000
- Cortical dysplasia;
Summary: Purpose: Human cortical dysplasia (CD) is a frequent cause of medically intractable focal epilepsy. The neurotransmitter mechanisms of epileptogenicity in these lesions have been attributed to changes in various glutamate receptor subtypes. Increased N-methyl-d-aspartate (NMDA) receptor (NR) 2A/B coassembled with NRI subunits has been shown in focal epileptic CD. The purpose of this study is to correlate in situ CD epileptogenicity and the expression of various glutamate receptor subtypes.
Methods: The histopathological, morphological, and immu-nocytochemical findings in cortical tissue resected from five patients with medically intractable epilepsy and CD were correlated with electroencephalographic data recorded from sub-dural grids. The NMDA antibodies identified subunits NRI (splicing variants la, lb, 2a, and 2b) and NR2A/B.
Results: Epileptogenic specimens displayed the following common features: (a) widespread histological abnormalities of horizontal and columnar dyslamination, neurons with inverted polarity, and more extensive dendritic changes; (b) significantly higher NR2A/B immunoreactivity in both the dysplastic somata and all their dendritic processes; and (c) no statistically significant change in NR1 subunit expression but a more pronounced staining of the apical dendrites in highly epileptogenic cortex. These abnormalities were either absent or minimal in resected specimens that did not show evidence of severe in vivo epileptogenicity.
Conclusion: These studies provide direct evidence for a major contribution of the NR2A/B subunit in CD-induced epileptogenicity.