Isoflurane enhanced hemorrhagic transformation by impairing antioxidant enzymes in hyperglycemic rats with middle cerebral artery occlusion
BACKGROUND AND PURPOSE: Because the potential neuroprotective effect of isoflurane is controversial, we attempted to study whether isoflurane after treatment provides neuroprotection in a rat model of hyperglycemia-induced ischemic hemorrhagic transformation. METHODS: Rats received an injection of 50% dextrose (6 mL/kg intraperitoneally) and had a middle cerebral artery occlusion 30 minutes later. Four groups were included: sham-operated, ischemia/reperfusion, isoflurane treatment, and vehicle groups. In the treatment group, after 2 hours of ischemia, 2% isoflurane was administered at the onset of reperfusion. We measured the level of blood glucose at 0, 2.5, 4.5, and 6.5 hours after dextrose injection. Infarct and hemorrhagic volumes, neurological scores, oxidative stress (malondialdehyde, 4-hydroxy-2-nonenal, and nitrotyrosine) and the activities of superoxide dismutase and catalase were measured at 24 hours after ischemia. RESULTS: Isoflurane had no effects on blood glucose, it failed to reduce infarct, hemorrhage volume, and brain edema, and it enhanced neurobehavioral deficits when compared with the ischemia/reperfusion group at 24 hours after middle cerebral artery occlusion. On the contrary, isoflurane exacerbated these parameters compared with the vehicle group. In addition, it increased the expressions of malondialdehyde, 4-hydroxy-2-nonenal, and nitrotyrosine, and it decreased the activities of superoxide dismutase and catalase compared to the vehicle group. CONCLUSIONS: Isoflurane after treatment worsened physiological and neurological outcomes in this ischemia hyperglycemia-induced hemorrhagic transformation possibly by impairing the antioxidant defense system.
Hu, Qin; Ma, Qingyi; Zhan, Yan; He, Zhaohui; Tang, Jiping; Zhou, Changman; and Zhang, John H., "Isoflurane enhanced hemorrhagic transformation by impairing antioxidant enzymes in hyperglycemic rats with middle cerebral artery occlusion" (2011). LLU Faculty Publications. 367.