[Background] It has been conflicting that nitrous oxide affected deteriorative or neuroprotective during cerebral ischemia, no conclusion has been evaluated. Therefore, in the present study, the effect of nitrous oxide on neuronal cell damage during cerebral ischemia was quantitatively evaluated by the ischemic duration causing 50% neuronal damage, and the relationships between ischemic depolarization and histological outcome were determined. Furthermore, the effect of nitrous oxide on dynamic change in extracellular glutamate concentration was also determined. [Materials and methods] Under 1% halothane anesthesia in 30% oxygen, fifty gerbils (weighing 71.0±5.6 g) were randomly assigned to a group receiving 70% nitrous oxide (N2O group, n=25) and a group receiving 70% nitrogen (N2 group, n=25). In the first experiment, forebrain ischemia was performed by occlusion of bilateral common carotid arteries for 3, 5 or 7 minutes (n=6 in each group). During ischemia, direct current potential was recorded from the bilateral hippocampal CA1 regions. Histological evaluation of bilateral hippocampal CA1 regions was performed 5 days after the ischemia. Relationships of neuronal damage with ischemic duration and duration of ischemic depolarization were determined by logistic regression curves. In the second experiment, forebrain ischemia was performed for 5 minutes by the same procedure as that used in the first experiment (n=7 in each group). Right hippocampal extracellular glutamate was measured using microdialysis and high-performance liquid chromatography every minute from 5 minutes before to 30 minutes after the ischemia. During the experimental period, nitrous oxide or nitrogen administration was continued, cerebral and rectal temperatures were maintained at 37.0±0.5 °C. [Results] Onset time of ischemic depolarization was shorter in the N2O group (1.65±0.46 minutes) than in the N2 group (1.92±0.38 minutes, p<0.01). In the case of 5-minute ischemia, the percentage of damaged neurons in the N2O group (81.5±22.4 %) was higher than that in the N2 group (38.9±13.3 %, p<0.01). Logistic regression curves in the N2O group shifted to the direction that neuronal damage was increased, ischemic durations causing 50% neuronal damage in the N2O group and N2 group were 4.43 minutes and 5.29 minutes, respectively (p<0.05). The 95% confidence intervals did not overlap from 3.80 to 5.85 minutes of ischemic duration and from 5.35 to 7.97 minutes of ischemic depolarization. There was no difference in both groups on dynamic change in extracellular glutamate concentration. Peak extracellular glutamate concentrations in the N2O group and N2 group were 61.0±39.6 mcM and 70.0±31.3 mcM, respectively (p=0.64). [Conclusion] Nitrous oxide accelerated neuronal damage during cerebral ischemia. In the N2O group, onset time was shorter and logistic regression curves were shifted to the direction that neuronal damage was increased compared with those in the N2 group. However, dynamic changes in extracellular glutamate concentration had no difference in the both groups. These results suggested that the acceleration of neuronal damage by nitrous oxide was predominantly affected by a factor other than the amount of extracellular glutamate release during ischemic depolarization.
|Journal||Journal of Cerebral Blood Flow and Metabolism|
|Issue number||SUPPL. 1|
|Publication status||Published - Nov 13 2007|
ASJC Scopus subject areas
- Clinical Neurology
- Cardiology and Cardiovascular Medicine