Effect of L-arginine and NG-nitro-L-arginine on delayed neuronal death in the gerbil hippocampus.
To assess the role of nitric oxide (NO) in cerebral ischemia, we investigated the effect of L-arginine, a substrate of NO synthase (NOS), and NG-nitro-L-arginine (L-NNA), a NOS inhibitor, on neuronal death in the CA1 hippocampal region. Seventy-two Mongolian gerbils were used in the study. Both carotid arteries were occluded for 4 min to induce forebrain ischemia. Temporal muscle temperature was strictly maintained at 37.5 +/- 0.3 degrees C during the ischemia. L-arginine (10 and 100 mg kg-1) or L-NNA (1, 10 and 100 mg kg-1) was administered intraperitoneally 4 times: 30 min before, 3 h, 6 h and 24 h after induction of ischemia. Four days after ischemic insult, the animals were perfusion-fixed, and the neuronal densities in the medial, middle and lateral CA1 subfield were estimated. Average neuronal cell density of the control group was 2-3 mm in each subfield. L-arginine at doses of 10 and 100 mg kg-1 did not prevent neuronal death. L-NNA at doses of 1 and 10 mg kg-1 did not protect neuronal cells from ischemia either. However, in ischemia gerbils treated with 100 mg kg-1 L-NNA, the average neuronal cell density in the lateral CA1 subfield was 54.4 +/- 19.1, L-NNA (100 mg kg-1) significantly (p < 0.05) reduced the occurrence of neuronal death in the lateral CA1 subfield. The present results suggest that NO plays an important role in the development of neuronal injury after global ischemia.
Nakagomi
T
T
Department of Neurosurgery, Teikyo University School of Medicine, Tokyo, Japan.
Kanemitsu
H
H
Takagi
K
K
Morikawa
E
E
Kirino
T
T
Tamura
A
A
D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D001831:Body Temperature; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005849:Gerbillinae; D006624:Hippocampus / Q000098:blood supply* / Q000166:cytology / Q000201:enzymology; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology*; D017693:Sodium Bicarbonate / Q000494:pharmacology
D004791:Enzyme Inhibitors; D019335:Nitroarginine; D017693:Sodium Bicarbonate; D001120:Arginine; D019001:Nitric Oxide Synthase