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Objective To compare the strength of oxidative stress from different concentrations of oxygen administered by the accumulation of hydroxyl radicals during early reperfusion after global brain ischemia.Methods Sixteen adult male Mongolian gerbils with microdialysis probes implanted in the hippocampal CA1 were divided randomly (random number)into two groups (n =8 in each).All gerbils of both groups were subjected to 10 min bilateral carotid artery occlusion (BCAO).Then the following intervention:(a) immediate 30% O2 (near normoxia,NO group ) and (b ) immediate 100% O2 (hyperoxia,HO group).The accumulation of hydroxyl radicals (·OH)in hippocampus during reperfusion was estimated by measuring 2,3-dihydroxybenzoic acid (DHBA ) and 2,5-DHBA in microdialysis perfusate.Results Immediately after the onset of reperfusion,two groups showed markedly elevated DHBA,which returned to baseline gradually.Compared with the NO group,the HO group showed significantly higher peak DHBA and slower recovery.Conclusions Hydroxyl radical accumulation was more sensitive to inhalation of high concentration O2 during early reperfusion of global cerebral ischemia.
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Aim To investigate the effect of fenofibrate on focal cerebral ischemia injury in rats and its mechanism.Methods The rat model of global cerebral ischemia/reperfusion injury was established by bilateral common carotid arteries occlusion combined with hemorrhagic hypotension.Fenofibrate (33, 100, 300 mg·kg~(-1)) was intragastriclly administered 30 min before the operation, MK886 (6 mg·kg~(-1)) was given intraperitoneally 30 min before administration of fenofibrate (300 mg·kg~(-1)).Morris water maze was used to evaluate the ability of spatial learning and memory function.HE staining was used to observe pathological morphological changes of hippocampal neurons. NF-κBp65 expression was detected by immunohistochemistry, SOD activities and MDA contents were analyzed by biochemistry, and IL-1β, IL-6, IL-10, TNF-α levels were detected by ELISA.Results Fenofibrate remarkably improved the spatial learning and memory function, obviously prevented the hippocampal neurons from karyopycnosis and losing induced by I/R. Fenofibrate significantly blunted the increase of MDA, NF-κBp65, TNF-α, IL-1β, IL-6, and the decrease of IL-10 and SOD activities of I/R rats.Conclusions Fenofibrate has an obviously neuroprotective effect on global cerebral ischemia/reperfusion damage by activating PPARα.The anti-inflammation and antioxidative stress of fenofibrate may be involved in the protective mechanism.