Epileptogenicity correlated with increased N-methyl-D-aspartate receptor subunit NR2A/B in human focal cortical dysplasia.
OBJECTIVE
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 NR1 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 immunocytochemical findings in cortical tissue resected from five patients with medically intractable epilepsy and CD were correlated with electroencephalographic data recorded from subdural grids. The NMDA antibodies identified subunits NR1 (splicing variants 1a, 1b, 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.


CONCLUSIONS
These studies provide direct evidence for a major contribution of the NR2A/B subunit in CD-induced epileptogenicity.
Najm
I M
IM
Department of Neurology, The Cleveland Clinic Foundation, Ohio 44195, USA. najmi@ccf.org
Ying
Z
Z
Babb
T
T
Mohamed
A
A
Hadam
J
J
LaPresto
E
E
Wyllie
E
E
Kotagal
P
P
Bingaman
W
W
Foldvary
N
N
Morris
H
H
Lüders
H O
HO
D000293:Adolescent; D000328:Adult; D002540:Cerebral Cortex / Q000002:abnormalities* / Q000737:chemistry / Q000503:physiopathology*; D004567:Electrodes, Implanted; D004569:Electroencephalography / Q000706:statistics & numerical data; D004828:Epilepsies, Partial / Q000175:diagnosis* / Q000503:physiopathology; D005260:Female; D005625:Frontal Lobe / Q000002:abnormalities / Q000737:chemistry / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging / Q000706:statistics & numerical data; D008297:Male; D016194:Receptors, N-Methyl-D-Aspartate / Q000032:analysis* / Q000378:metabolism; D015854:Up-Regulation
C409466:NR1 NMDA receptor; C120997:NR2A NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate