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OBJECTIVE To determine spatio-temporal properties of 5-lipoxygenase (5-LOX) expression and the effect of zileuton, a selective 5-LOX inhibitor, on the hippocampal neuron injury following global cerebral ischemia (GCI).METHODS GCI 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 immunoflurescence.The 5-LOX inhibitor zileuton (10, 30, 50 mg· kg-1) were orally administered.RESULTS The 5-LOX expression was significantly upregulated in the hippocampus 1, 3 and 7 d (peaked at 3 d) after ischemia.In the hippocampal CA1 region, 5-LOX protein was primarily localized in the neurons.The 5-LOX inhibitor zileuton (30, 50 mg·kg-1) markedly reduced hippocampal CA1 neuron damage at 3 d after ischemia.Protective effect of zileuton (30 mg· kg-1, 7 consecutive days) is still evident 14 d after the ischemia episode.CONCLUSION 5-LOX is involved in global cerebral ischemic damage, the 5-LOX selective inhibitor zileuton possesses neuroprotective effect on neuronal damage in the rat hippocampus following GCI.