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Nitric oxide synthase and NMDA receptor expressions in cavernoma tissues with epileptogenesis


Tohru Kamida, Department of Neurosurgery, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Oita 879-5593, Japan
Tel.: 81-97-586-5862; Fax: 81-97-586-5869;


Objectives –  To investigate the contribution of nitric oxide (NO) and the glutamate systems to epileptogenicity of cavernoma (CA).

Methods –  Using immunohistochemistry we examined NO synthases (NOS; neuronal, inducible and endothelial) and N-methyl-D-aspartate (NMDA) receptor subunits 1(NR1) and 2A/B (NR2A/B) in tissues, with and without hemosiderin deposits, adjacent to CA resected from temporal (seven patients) and frontal (one patient) lobes.

Results –  All isoforms of NOS, especially iNOS expression, was significantly upregulated in company with NR2A/B expression, not only in declining neuronal cells but also in reactive astrocytes in the tissue, with hemosiderin deposits, adjacent to CA and moreover the degree of iNOS expression was significantly correlated with seizure frequency.

Conclusions –  These preliminary results sustain a speculation that excessive NO may generate in the tissue surrounding CA with repeated microhaemorrhaging and seizures. The neuronal loss and reactive glial proliferation induced by iron or NO may play a role in epileptogenesis.