Minako Arai

Dynamic changes in cortical NADH fluorescence in rat focal ischemia: evaluation of the effects of hypothermia on propagation of peri-infarct depolarization by temporal and spatial analysis.

Suppression of peri-infarct depolarizations (PIDs) is one of the major mechanisms of hypothermic protection against transient focal cerebral ischemia. Previous studies have shown the lack of hypothermic protection against permanent focal ischemia. We hypothesized the lack of hypothermic protection was due to the poor efficacy in suppression of PIDs. To examine the hypothesis, we elucidated the effects of hypothermia on the manner of propagation of PIDs with temporal and spatial resolutions using NADH (reduced nicotinamide adenine dinucleotide) fluorescence images by illuminating the parietal-temporal cortex with ultraviolet light. Spontaneously hypertensive rats (n=14) were subjected to permanent focal ischemia by occlusion of the middle cerebral and left common carotid arteries. 2-h hypothermia (30 degrees C) was initiated before ischemia. Although hypothermia delayed the appearance of PIDs, it did not suppress their appearance. Furthermore, 54% of the PIDs enlarged the high-intensity area of NADH fluorescence in the hypothermia group, similar to the normothermia group (53%). The high-intensity area of NADH fluorescence widened by each PID was larger in the hypothermia group than in the normothermia group. These findings suggest that PIDs even in hypothermia are one of the major factors causing growth of infarction, emphasizing the importance of therapy that targets suppression of PIDs even during hypothermia.

Effect of nitrous oxide on neuronal damage and extracellular glutamate concentration as a function of mild, moderate, or severe ischemia in halothane-anesthetized gerbils.

Background:The effect of nitrous oxide on ischemic neuronal damage was quantitatively evaluated by use of logistic regression curves. Methods:Seventy-two gerbils were anesthetized with 1% halothane and randomly assigned to receive 70% nitrous oxide or 70% nitrogen. Forebrain ischemia was performed for 3, 5, or 7 min, and direct-current potential in the hippocampal CA1 region was recorded. Histologic outcome was evaluated 5 days later. Relations of neuronal damage with ischemic duration and duration of ischemic depolarization were determined by logistic regression curves. In some animals, extracellular glutamate concentration was measured every 60 s during forebrain ischemia. Results:Nitrous oxide increased neuronal damage only with 5 min of ischemia (nitrous oxide vs. nitrogen: 78.5 ± 23.0 vs. 37.3 ± 12.2%; P < 0.01). The percentages of neuronal damage with 3 and 7 min of ischemia were not different with or without nitrous oxide. Logistic regression curves indicated that nitrous oxide significantly increased neuronal damage during the period from 3.07 to 6.63 min of ischemia. Logistic regression curves also indicated that nitrous oxide increased neuronal damage in the condition of the same duration of ischemic depolarization. Nitrous oxide shortened the ischemic duration necessary for causing 50% neuronal damage by 0.82 min. Dynamic change in extracellular glutamate concentration was not different (mean maximum dialysate glutamate concentration: 4.29 ± 3.09 vs. 4.63 ± 1.83 &mgr;m). Conclusion:Administration of nitrous oxide caused an increase in ischemic neuronal damage, but a significant adverse effect was observed with a limited range of ischemic intervals.