Postischemic application of lipid peroxidation inhibitor U-101033E reduces neuronal damage after global cerebral ischemia in rats, Stroke 29

Background and Purpose—The lipid peroxidation inhibitor U-101033E was examined for effects on cerebral blood flow (CBF), cortical tissue hemoglobin oxygen saturation (HbSO2), and neuronal damage. Methods—Fifteen minutes of global cerebral ischemia was induced by two-vessel occlusion and hypobaric hypotension. Wistar rats (n525) were randomized to receive vehicle (n59) or 40 mg/kg U-101033E (n59) intraperitoneally during 2 hours of reperfusion. A sham group (n57) had neither ischemia nor therapy. Histology was evaluated 7 days after ischemia. Results—During late hyperperfusion (at 17 minutes), vehicle-treated animals had a higher (P50.044) cortical tissue HbSO2 (72.061.4%) than did U-101033E–treated animals (65.862.5%). Neuronal counts in the superficial cortex layer found after 7 days correlated negatively with rCBF (r520.76; P,0.001) or cortical tissue HbSO2 (r520.56; P50.028) assessed during the late hyperperfusion phase. U-101033E reduced neuronal damage in hippocampal CA1 from 64.369.2 % to 31.268.4 % (P50.020), as well as in the superficial cortical layer from 53.5614.6 % to 12.8611.7% (P50.046). While animals in the vehicle group had reduced counts in all four examined cortex layers (P,0.05 versus sham group), there was significant cortical neuron loss in the U-101033E group in only one of four areas. U-101033E had no effect on resting CBF or CO2 reactivity. Conclusions—Postischemic application of U-101033E protects hippocampal CA1 and cortical neurons after 15 minutes o