1 The aim of this study was to investigate whether delayed treatment with the anti-oxidant and antiin¯ammatory agent ebselen reduces the volume of infarction in a rodent model of permanent focal cerebral ischaemia. 2 Ebselen (10 or 30 mg kg 71 ) or vehicle was administered by gavage 30 min and 12 h after the induction of cerebral ischaemia by permanent occlusion of the left middle cerebral artery (MCA). Animals were killed 24 h following MCA occlusion, and the volumes of ischaemic damage in the ebselen and control groups were evaluated by quantitative histopathology. 3 Ebselen was quickly absorbed following oral (gavage) administration and reached peak levels in the plasma by 1 h post-administration (plasma selenium level of 0.68+0.04 and 0.84+0.1 mg ml 71 for 10 and 30 mg kg
71, respectively, compared to control level of 0.51+0.02 mg kg
71). 4 Treatment with the lower dose of ebselen (10 mg kg 71 ) signi®cantly (P50.01) reduced the volume of infarction in the cerebral hemisphere and cerebral cortex (by 31.8% and 36.7%, respectively compared with the placebo group). 5 The neuroprotective ecacy of the higher dose ebselen (30 mg kg 71 ) was less than that of the lower dose ebselen (10 mg kg 71 ). The volume of ischaemic damage in the cerebral hemisphere was reduced by 23.7% (P50.02), and cerebral cortex by 27.5% (P50.01). 6 Both doses of ebselen (10, 30 mg kg
71) had no therapeutic ecacy on the caudate nucleus, where ischaemia was most severe, in this model. 7 Free radical-mediated injury is normally associated with reperfusion of ischaemic tissue. The present results suggest that oxidative injury is also a signi®cant contributor to brain damage in models of maintained (permanent) ischaemia and that ebselen is eective in attenuating this free radical-induced damage.
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