Nitric oxide synthase inhibitor reduces delayed neuronal death in gerbil hippocampal CA1 neurons after transient global ischemia without reduction of brain temperature or extracellular glutamate concentration.
We planned a study to determine whether or not the mechanism of nitric oxide (NO) neurotoxicity involves the elevation of extracellular glutamate or changes of brain temperature in the pathogenesis of delayed neuronal death of gerbil hippocampal CA1 neurons following 5-min transient forebrain ischemia. Intraventricular injection of 5 microliters of 5.0 mg/ml N omega-nitro-L-arginine (LNNA) significantly preserved neuronal density in the central part of the CA1 region examined 7 days after 5-min ischemia [188.5 +/- 8.5/mm: 90.0% of the 209.5 +/- 11.1/mm density in the sham-operated controls vs. 16.7 +/- 6.4/mm in those injected with artificial cerebrospinal fluid (CSF) only]. There was no difference between these two groups in hippocampal temperature before, during or after 5-min ischemia. The glutamate concentration ([Glu]) during 5-min ischemia measured by a microdialysis technique was similar in the two groups (peak [Glu.] = 2.76 +/- 0.62 pmol/microliters dialysate in the artificial CSF group and = 2.93 +/- 0.64 pmol/microliters dialysate in the LNNA group). It was found that the neuronal toxicity of NO does not involve hyperthermia or the increase of extracellular glutamate concentration in the hippocampal CA1 region during 5-min ischemia.
Kohno
K
K
Department of Neurological Surgery, Ehime University School of Medicine, Japan.
Ohta
S
S
Kohno
K
K
Kumon
Y
Y
Mitani
A
A
Sakaki
S
S
Kataoka
K
K
D000704:Analysis of Variance; D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005849:Gerbillinae; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine / Q000627:therapeutic use
D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D019335:Nitroarginine; D018698:Glutamic Acid; D019001:Nitric Oxide Synthase