Kenshi Kaneko and Kouichi Itoh contributed equally to this work.
Consequences of nitric oxide generation in epileptic-seizure rodent models as studied by in vivo EPR
Article first published online: 3 DEC 2002
Copyright © 2002 Wiley-Liss, Inc.
Magnetic Resonance in Medicine
Volume 48, Issue 6, pages 1051–1056, December 2002
How to Cite
Kaneko, K., Itoh, K., Berliner, L. J., Miyasaka, K. and Fujii, H. (2002), Consequences of nitric oxide generation in epileptic-seizure rodent models as studied by in vivo EPR. Magn Reson Med, 48: 1051–1056. doi: 10.1002/mrm.10297
- Issue published online: 3 DEC 2002
- Article first published online: 3 DEC 2002
- Manuscript Accepted: 31 JUL 2002
- Manuscript Revised: 17 JUL 2002
- Manuscript Received: 29 MAR 2002
- Japan Society for the Promotion of Science (JSPS)
- in vivo;
- pentylenetetrazole (PTZ)
The role of nitric oxide (NO) in epileptogenesis was studied in pentylenetetrazole (PTZ)-treated animals using in vivo and ex vivo EPR spectroscopy. NO generation was measured directly in the brain of a PTZ-induced mouse in vivo by an L-band EPR spectrometer. An elevation in NO production in the brain was observed during convulsions, and more NO was generated in the tonic seizure vs. the clonic seizure. NO content in several brain tissues (including the cerebral cortex (CR), cerebellum (CL), olfactory bulb (OB), hippocampus (HI), and hypothalamus (HT)) of PTZ-doped rats was analyzed quantitatively ex vivo by X-band EPR. To test the involvement of NO in seizure development, pharmacological analyses were performed using the NO synthase (NOS) inhibitors NG-nitro-L-arginine (L-NNA), NG-monomethyl-L-arginine (L-NMMA), and 3-bromo-7-nitroindazole (3Br-7NI). All of these inhibitors suppressed the convulsions, holding them at the clonic level, and prevented development of a tonic convulsion in rats doped with up to 80 mg/kg PTZ. 3Br-7NI completely inhibited NO production, but L-NNA and L-NMMA showed only 70% inhibition of NO production in PTZ-doped rats. In order to examine the contributions of NO in convulsions, rats were treated with anticonvulsants (phenytoin and diazepam) before PTZ treatment. Both drugs completely suppressed tonic convulsion in PTZ-doped rats at doses up to 80 mg/kg, but NO levels were similar to those detected in a clonic convulsion. These results support the notion that NO does not directly induce a clonic convulsion, but may be generated as a consequence of onset of seizure. Magn Reson Med 48:1051–1056, 2002. © 2002 Wiley-Liss, Inc.