Increased nitric oxide caused by the ketogenic diet reduces the onset time of kainic acid-induced seizures in ICR mice

• Published in: Brain research 2006-02, Vol.1075 (1), p.193-200
• Main Authors: Noh, Hae Sook, Kim, Dong Wook, Cho, Gyeong Jae, Choi, Wan Sung, Kang, Sang Soo
• Format: Article
• Language: English
• Subjects: 3-Hydroxybutyric Acid - blood; 7-nitroindazole; Animal Feed; Animals; Anticonvulsants - pharmacology; Biological and medical sciences; Diet; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Immunohistochemistry; Kainic Acid; Ketogenic diet; Ketone Bodies; Male; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Inbred ICR; N-ω-nitro- l-arginine methyl ester; Nervous system (semeiology, syndromes); Neurology; NG-Nitroarginine Methyl Ester - pharmacology; Nitric oxide; Nitric Oxide - physiology; Nitric Oxide Donors - pharmacology; Nitric Oxide Synthase - metabolism; NOS-knockout mice; Seizures - chemically induced; Seizures - prevention & control
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2005.12.017

Although the antiepileptic effects of the ketogenic diet (KD) are well documented, the mechanisms underlying this action remain obscure. Nitric oxide (NO) has long been thought to play a role in regulating seizures. However, the effects of the KD on endogenous NO production have not been characterized. Therefore, the present study was designed to examine the effect of the KD on endogenous NO production, as well as the precise role of NO in kainic acid (KA)-induced seizures, in male ICR mice. We first found that preadministration of the KD for 4 weeks increased endogenous NO generation in the hippocampus. We also demonstrated that the increase in NO induced by the KD resulted from increased neuronal NO synthase (nNOS) activity and exerted an antiepileptic effect on KA-induced seizures, based on the results of experiments using NOS-knockout mice and two NOS inhibitors, N-ω-nitro- l-arginine methyl ester ( l-NAME) and 7-nitroindazole (7-NI). These data suggest that the antiepileptic effects of the KD might be mediated, at least in part, by increased NO levels in the hippocampus.