OBJECTIVETo determine 5-lipoxygenase (5-LOX) expression and the effect of zileuton, a selective 5-LOX inhibitor,on hippocampal neuron injury induced by global cerebral ischemia in rats.

METHODSGlobal cerebral ischemia was induced by bilateral common carotid artery occlusion combined with hypotension in rats. 5-LOX expression was detected by Western blot analyses and 5-LOX localization was visualized by immunohistochemistry and double immunofluorescence methods. The 5-LOX inhibitor zileuton (10, 30, 50 mg/kg) was orally administered for 3 d after ischemia.

RESULTSThe 5-LOX expression was increased in the ischemic hippocampus on d1-7 (peaked at d3), and 5-LOX protein was primarily localized in neurons and translocated to the nuclei in the hippocampal CA1 region after ischemia. The 5-LOX inhibitor zileuton (30, 50 mg/kg) reduced ischemia-induced hippocampal neurons death 3d after ischemia.

CONCLUSION5-LOX is involved in global cerebral ischemic damage in rats, and the 5-LOX inhibitor zileuton has a protective effect on neuronal damage in the rat hippocampus following global cerebral ischemia.

Animals ; Arachidonate 5-Lipoxygenase ; metabolism ; physiology ; Brain Ischemia ; metabolism ; pathology ; CA1 Region, Hippocampal ; metabolism ; pathology ; Disease Models, Animal ; Hydroxyurea ; analogs & derivatives ; pharmacology ; Lipoxygenase Inhibitors ; pharmacology ; Male ; Neurons ; drug effects ; pathology ; Rats ; Rats, Sprague-Dawley