Kaneko Kenshi, Itoh Kouichi, Berliner Lawrence J, Miyasaka Kazuo, Fujii Hirotada
Department of Radiology, Hokkaido University School of Medicine, Hokkaido, Japan.
Magn Reson Med. 2002 Dec;48(6):1051-6. doi: 10.1002/mrm.10297.
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 N(G)-nitro-L-arginine (L-NNA), N(G)-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.
利用体内和体外电子顺磁共振波谱技术，在戊四氮（PTZ）处理的动物中研究了一氧化氮（NO）在癫痫发生中的作用。通过L波段电子顺磁共振波谱仪直接在体内测量PTZ诱导的小鼠大脑中的NO生成。在惊厥期间观察到大脑中NO生成增加，并且强直发作时比阵挛发作时产生更多的NO。通过X波段电子顺磁共振对PTZ掺杂大鼠的几种脑组织（包括大脑皮层（CR）、小脑（CL）、嗅球（OB）、海马体（HI）和下丘脑（HT））中的NO含量进行了体外定量分析。为了测试NO在癫痫发作发展中的作用，使用一氧化氮合酶（NOS）抑制剂N（G）-硝基-L-精氨酸（L-NNA）、N（G）-单甲基-L-精氨酸（L-NMMA）和3-溴-7-硝基吲唑（3Br-7NI）进行了药理学分析。所有这些抑制剂都抑制了惊厥，将其维持在阵挛水平，并防止了高达80mg/kg PTZ掺杂大鼠中强直惊厥的发展。3Br-7NI完全抑制了NO生成，但L-NNA和L-NMMA在PTZ掺杂大鼠中仅显示出70%的NO生成抑制。为了研究NO在惊厥中的作用，在PTZ治疗前用抗惊厥药（苯妥英和地西泮）对大鼠进行了治疗。两种药物在高达80mg/kg的剂量下都完全抑制了PTZ掺杂大鼠中的强直惊厥，但NO水平与阵挛惊厥中检测到的水平相似。这些结果支持了NO不会直接诱发阵挛惊厥，但可能是癫痫发作开始的结果而产生的这一观点。
