In this model of transient focal cerebral ischemia, xenon administration improved both functional and histologic outcome.

N-Methyl-D-aspartate receptor antagonism contributes to the anesthetic action of nitrous oxide (N(2)O). We examined the effects of the N-methyl-D-aspartate antagonists N(2)O and dizocilpine on outcome from filament occlusion of the middle cerebral artery (MCAO). Rats breathed 70% nitrogen/30% oxygen or 70% N(2)O/30% oxygen during MCAO. A third group breathed 70% nitrogen/30% oxygen and was given dizocilpine (0.25 mg/kg IV). After 75 min of MCAO, the rats recovered for 3 or 14 days. Pericranial temperature was maintained at 37.5 degrees C +/- 0.2 degrees C during ischemia and for 20 h postischemia. N(2)O did not alter neurologic scores at 3 days (N(2)O, 21 +/- 6; nitrogen, 22 +/- 8; P = 0.95; 0 = normal; 48 = maximal deficit; mean +/- sd; n = 15) or 14 days (N(2)O, 13 +/- 6; nitrogen, 12 +/- 6; P = 0.93; n = 15-16) postischemia. N(2)O had no effect on infarct size at 3 days (N(2)O, 162 +/- 45 mm(3); nitrogen, 162 +/- 61 mm(3); P > 0.99) or 14 days (N(2)O, 147 +/- 56 mm(3); nitrogen, 151 +/- 62 mm(3); P = 0.99) postischemia. Dizocilpine treatment caused smaller infarcts (3 days: 66 +/- 49 mm(3), P < 0.0001 versus nitrogen; 14 days: 84 +/- 50 mm(3), P < 0.006 versus nitrogen) and reduced the neurologic deficit (3 days: 10 +/- 10, P = 0.002 versus nitrogen; 14 days: 6 +/- 7, P = 0.006 versus nitrogen). N(2)O (70%) had no effect on either behavioral or histologic outcome from transient focal cerebral ischemia when compared with results in rats breathing 70% nitrogen. These results indicate that normobaric N(2)O does not alter the response of rat brain to a focal ischemic insult.

Isoflurane improves outcome against cerebral ischemia in the rat. However, the optimal neuroprotective concentration has not been defined. We examined the effects of different isoflurane concentrations on outcome from severe forebrain ischemia in the rat. Fasted rats were subjected to 0.5, 1.0, 1.5, 2.0, or 2.5 minimum alveolar concentration (MAC) isoflurane during 10 min bilateral carotid occlusion plus systemic hypotension. Each isoflurane concentration was administered only before ischemia. Arterial blood pressure was not pharmacologically manipulated. After ischemia, the anesthetic regimen was changed to fentanyl/nitrous oxide and maintained for 2 h. Pericranial temperature was maintained normothermic during the experiment. Neuromotor score, % dead hippocampal CA1 neurons, and cortical injury were measured 5 days postischemia. Preischemic arterial blood pressure decreased as MAC was increased. Animals administered >1.0 MAC frequently exhibited postischemic seizures resulting in increased mortality. There was no difference among MAC conditions for % dead CA1 neurons (93 approximately 95%). In the cortex, neuronal necrosis was less severe with 0.5 MAC and 1.0 MAC isoflurane relative to >1.0 MAC values. The neuromotor score in the 1.0 MAC isoflurane group was superior to the 2.5 MAC group. Dose-dependent effects of preischemic administration of isoflurane on histologic and behavioral outcome after severe forebrain ischemia were observed. Isoflurane MAC values <1.5 provided superior overall outcome relative to larger isoflurane concentrations.