Effects of deep hypothermia on nitric oxide-induced cytotoxicity in primary cultures of cortical neurons.
Nitric oxide (NO) is thought to play a major role during cerebral ischemia. However, the protective efficacy of hypothermia against NO-induced neurotoxicity remains to be examined. In the present study, the degree of neurotoxicity induced by NO was analyzed in two temperature groups (normothermia, 37 degrees C; deep hypothermia, 22 degrees C) of cultured E16 Wistar rat cortical neurons. Two different NO donors, 1-hydroxy-2-oxo-3-(N-ethyl-2-aminoethyl)-3-ethyl-1-triazene (NOC-12) and 1-hydroxy-2-oxo-3-(3-amynopropyl)-3-isopropyl-1-triazene (NOC-5), that have equal half-lives at 37 degrees C and 22 degrees C, respectively, were used. Cultured neurons in each temperature group were exposed to 30 and 100 micro M NOC for three different time courses, 6 hr, 12 hr, and 24 hr. The survival rates of neurons were evaluated by assessing viable neurons on photomicrographs before and after the experiments. The highest survival rate (approximately 93%) was seen in both temperature groups when neurons were exposed to 30 micro M NOC for 6 hr and 12 hr, and there was no significant difference observed between these two groups (P > 0.05). Almost equal survival rates were observed in both temperature groups following exposure to 30 micro M NOC for 24 hr (at 37 degrees C, 80.4% +/- 2.6%; at 22 degrees C, 83.2% +/- 1.6%; P > 0.05). During exposure to 100 micro M NOC, although the survival rate linearly decreased (approximately from 70% to 5%) in both temperature groups when exposed for 6-24 hr, there were no significant intergroup differences observed (P > 0.05). In conclusion, hypothermia does not provide adequate protection to the neurons by acting on the mechanisms evoked by NO, so we speculate that hypothermia may not confer neuroprotetcion once NO is released during ischemia.
Varathan
Sriranganathan
S
Department of Anesthesiology, Osaka University Graduate School of Medicine, Osaka, Japan. varathansr@yahoo.co.uk
Shibuta
Satoshi
S
Varathan
Vidya
V
Takemura
Motohide
M
Yonehara
Norifumi
N
Mashimo
Takashi
T
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D004334:Drug Administration Schedule; D005333:Fetus; D007036:Hypothermia, Induced; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009498:Neurotoxins / Q000378:metabolism* / Q000633:toxicity; D009569:Nitric Oxide / Q000378:metabolism* / Q000633:toxicity; D020030:Nitric Oxide Donors / Q000633:toxicity; D051381:Rats
D009498:Neurotoxins; D020030:Nitric Oxide Donors; D009569:Nitric Oxide