XXXX in blood and brain tissue following intra-carotid injections in normal and @entity64 -induced @entity35 .

@entity64 @entity2806 @entity63 @entity2500 @entity870 @entity205 @entity1188 @entity35
Administration of @entity205 ( @entity870 ) to @entity35 undergoing reversible global or focal @entity63 has been demonstrated to be variably neuroprotective. As @entity870 does not readily cross the blood-brain barrier, the variability may be due to differences in bioavailability of @entity870 to the @entity63 brain. We have, therefore, quantitated @entity870 levels in blood and brain following intra-carotid injection in @entity35 undergoing permanent right @entity2500 using a three-vessel model of focal @entity2806 . After 30 min of three-vessel occlusion, @entity870 (10 mg/kg) was injected into the left external carotid artery followed by reversal of the left common carotid artery occlusion. At various times post-injection, blood samples were collected from the vena cava and samples of @entity63 or sham-operated cortex were obtained for @entity870 quantitation by tandem mass spectrometry. Pharmacokinetic parameters were determined using non-linear mixed-effects modeling. @entity870 areas under the curve between normal and @entity64 -induced @entity35 were not significantly different in blood (18355 vs. 19405 ng x h/ml, NS) or in brain tissue (15664 vs. 14931 ng x h/g, NS). These results demonstrate that intra-carotid injection of @entity870 results in high levels in brain (brain-blood ratio from 0.5 to 1). No significant differences in blood and brain exposure were observed between normal and @entity64 -induced @entity35 . Therefore, reduced cerebral blood flow in the @entity63 territory did not limit @entity870 availability to the cortex. In addition, @entity870 intra-carotid administration was neuroprotective following 24 h recovery as there was a significant decrease in the @entity1188 area of the affected hemisphere compared to saline injected @entity35 as estimated by TTC staining of viable tissue.
