Upregulation of glutamate receptors in rat cerebral cortex with neuronal migration disorders.
Neuronal migration disorders (NMDs) constitute the main pathologic substrate of medically intractable epilepsy in human. This study is designed to investigate the changes in expression of glutamate receptor subtypes on radiation-induced NMD in rats. The lesion was produced by intrauterine irradiation (240 cGy) on E17 rats, and then 10 weeks old rats were used for the study. The pathologic and immuno-histochemical findings for glutamate receptor subunit proteins on NMD cortex were correlated with development of behavioral seizures and EEG abnormality. Spontaneous seizures uncommonly occurred in NMD rats (5%); however, clinical stages of seizures were significantly increased in NMD rats by an administration of kainic acid. Brains taken from irradiated rats revealed gross and histopathologic features of NMD. Focal cortical dysplasia was identified by histopathology and immunohistochemistry with neurofilament protein (NF-M/H). Significantly strong NR1 and NR2A/B immunoreactivities were demonstrated in cytomegalic and heterotopic neurons of NMD rats. The results of the present study indicate that epileptogenesis of NMD might be caused by upregulation of glutamate receptor expression in dysplastic neurons of the rat cerebral cortex with NMDs.
Lee
Min-Cheol
MC
Department of Pathology, Chonnam National University Medical School, Gwangju, Korea. mclee@jnu.ac.kr
Shim
Jae-Jin
JJ
Kim
Jae-Hyoo
JH
Kim
Myeong-Kyu
MK
Woo
Young-Jong
YJ
Chung
Woong-Ki
WK
Suh
Jung-Jin
JJ
Nam
Sang-Chae
SC
Lee
Ji-Shin
JS
Kim
Yeong-Seon
YS
Kim
Jin-Hee
JH
Kim
Hyoung-Ihl
HI
D000818:Animals; D002465:Cell Movement; D002540:Cerebral Cortex / Q000378:metabolism*; D004569:Electroencephalography; D018698:Glutamic Acid / Q000378:metabolism; D007150:Immunohistochemistry; D007608:Kainic Acid / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis*; D013997:Time Factors; D015854:Up-Regulation
C409466:NR1 NMDA receptor; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D007608:Kainic Acid