| Objective: To investigate the change of metal ion levels (Cu, Zn, Mn, Fe and Al) of global cerebral ischemia/reperfusion rat cortex and its mechanism.Methods: The rat model of global cerebral ischemia/reperfusion was established by bilateral common carotid arteries occlusion combined with haemospasia hypotension. Morris water maze was used to evaluate the ability of spatial learning and memory function of rats. Pathomorphology changes of cortical neurons were observed by HE staining. The cortical metal ion level was determined by inductively coupled plasma optical emission spectrometer (ICP-OES). The dye Evans blue was used to monitor the blood-brain barrier permeability of the rat brain. COX-2, 5-LO, MMP-2, MMP-9, and DMT-1 expression in rat cortex were detected by immunohistochemistry, and transferrin level was measured by Elisa. The COX-2 inhibitor meloxicam (1 mg·kg-1 and 5 mg·kg-1) and 5-LO inhibitor caffeic acid (10 mg·kg - 1 and 50 mg·kg - 1) were intraperitoneally administered 30 min before I/R, respectively. Results: The spatial learning and memory function of model rats was significantly impaired compared with that of sham group. In model rats, cortical neurons showed obviously karyopycnosis and loss. The metal ion levels (Fe, Mn, Al, Cu and Zn) in cortex remarkably increased after global cerebral I/R in rats, and still in 30d after I/R. Meloxicam and caffeic acid significantly prevented rats from learning and memory function impairment and cortical neuron damage induced by I/R rats. Meloxicam and caffeic acid also obviously decreased the metal ion concentration and blood-brain barrier permeability and downregulated the cortical neuronal expression of DMT-1, MMP-2, MMP-9, COX-2, and 5-LO as well as the transferrin level.Conclusions: The metal ion levels in cortical neuron significantly increased in global cerebral I/R rats. The mechanism may be related to the inflammatory reaction and the increasing of blood-brain barrier permeability induced by global cerebral I/R.
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