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(Stroke. 1998;29:1240-1247.)
© 1998 American Heart Association, Inc.

Original Contributions

Postischemic Application of Lipid Peroxidation Inhibitor U-101033E Reduces Neuronal Damage After Global Cerebral Ischemia in Rats

Martin Soehle, cand. med.; Axel Heimann, DVM; Oliver Kempski, MD, PhD

From the Institute for Neurosurgical Pathophysiology, Johannes Gutenberg University, Mainz, Germany.

Correspondence toUniv-Prof Dr med O. Kempski, Institute for Neurosurgical Pathophysiology, Johannes Gutenberg University, Langenbeckstr 1, 55101 Mainz, Germany. E-mail kempski{at}nc-patho.klinik.uni-mainz.de

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 (n=25) were randomized to receive vehicle (n=9) or 40 mg/kg U-101033E (n=9) intraperitoneally during 2 hours of reperfusion. A sham group (n=7) 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 (P=0.044) cortical tissue HbSO₂ (72.0±1.4%) than did U-101033E–treated animals (65.8±2.5%). Neuronal counts in the superficial cortex layer found after 7 days correlated negatively with rCBF (r=-0.76; P<0.001) or cortical tissue HbSO₂ (r=-0.56; P=0.028) assessed during the late hyperperfusion phase. U-101033E reduced neuronal damage in hippocampal CA1 from 64.3±9.2% to 31.2±8.4% (P=0.020), as well as in the superficial cortical layer from 53.5±14.6% to 12.8±11.7% (P=0.046). 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 of global cerebral ischemia. The results indicate that free radical–induced lipid peroxidation contributes to reperfusion injury, a process that can be inhibited by antioxidants such as U-101033E.

Editorial Comment

Costantino Iadecola, MD, Guest Editor

University of Minnesota, Laboratory of Cerebrovascular Biology and Stroke, Department of Neurology, Minneapolis, Minnesota

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