Increased nitric oxide caused by the ketogenic diet reduces the onset time of kainic acid-induced seizures in ICR mice.
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-omega-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.
Noh
Hae Sook
HS
Department of Anatomy and Neurobiology, Institute of Health Science, College of Medicine, Gyeongsang National University, 92 Chilam-dong, Jinju, Kyungnam 660-751, South Korea.
Kim
Dong Wook
DW
Cho
Gyeong Jae
GJ
Choi
Wan Sung
WS
Kang
Sang Soo
SS
D020155:3-Hydroxybutyric Acid / Q000097:blood; D000821:Animal Feed; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D004032:Diet; D007150:Immunohistochemistry; D007608:Kainic Acid; D007657:Ketone Bodies; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced* / Q000517:prevention & control*
D000927:Anticonvulsants; D007657:Ketone Bodies; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D007608:Kainic Acid; D020155:3-Hydroxybutyric Acid; D019331:NG-Nitroarginine Methyl Ester