Postischemic application of lipid peroxidation inhibitor U-101033E reduces neuronal damage after global cerebral ischemia in rats.
OBJECTIVE
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.
Soehle
M
M
Institute for Neurosurgical Pathophysiology, Johannes Gutenberg University, Mainz, Germany.
Heimann
A
A
Kempski
O
O
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002245:Carbon Dioxide / Q000494:pharmacology; D002452:Cell Count; D002560:Cerebrovascular Circulation / Q000187:drug effects; D007022:Hypotension / Q000503:physiopathology; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D017078:Laser-Doppler Flowmetry; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D009474:Neurons / Q000166:cytology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010108:Oxyhemoglobins / Q000032:analysis; D011743:Pyrimidines / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology
D000975:Antioxidants; D018696:Neuroprotective Agents; D010108:Oxyhemoglobins; D011743:Pyrimidines; D011759:Pyrrolidines; C101923:U 101033E; D014665:Vasodilator Agents; D002245:Carbon Dioxide