Inhibition of nitric oxide production during global ischemia ameliorates ischemic damage of pyramidal neurons in the hippocampus.
We examined the relationship between nitric oxide (NO) production and delayed neuronal death (DND), in the rat hippocampus induced by 21 minutes of transient global ischemia produced by the occlusion of both of the common carotid arteries combined with systemic hypotension. NO production during ischemia and reperfusion was investigated by quantifying the nitrite (NO2-) levels of the in vivo microdialysis samples collected ever 3 minutes from the hippocampus. To determine the origin of NO production, we studied the effects of the focal administration of NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of the constitutive NO synthase (NOS). We also carried out systemic administration of a selective neuronal NOS inhibitor, 7-nitroindazole (7-NI). Rats were grouped as follows: group 1 (n = 22), vehicle; group 2 (n = 19), L-NAME; group 3 (n = 12), 7-NI; and group 4 (n = 12), a sham operation. The role of NO in the hippocampal DND was investigated histologically one week after ischemia. The level of NO production was significantly decreased in groups 2 and 3 as compared to group 1 in which NO production was significantly increased (p < 0.05). The density of remaining neurons in the CA1 area was significantly reduced only in group 1 (p < 0.01). Taken together, it can be concluded that NO production by neuronal NOS during ischemia and reperfusion resulted in DND in the CA1 region of the rat hippocampus.
Sasaki
T
T
Department of Neurology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. tsasaki@med.keio.ac.jp
Hamada
J
J
Shibata
M
M
Araki
N
N
Fukuuchi
Y
Y
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology*; D016923:Cell Death; D006624:Hippocampus / Q000473:pathology*; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D017966:Pyramidal Cells / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar
D007191:Indazoles; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester