Neuroprotection and glutamate attenuation by acetylsalicylic acid in temporary but not in permanent cerebral ischemia

To assess the effects of acetylsalicylic acid (ASA) on glutamate and interleukin-6 (IL-6) release in the striatum of rats suffering from cerebral ischemia, we used the microdialysis technique with probes implanted 2 h Prior to stroke onset. A total of 36 rats were randomly assigned to either temporary (90 min, n= 18) or permanent (n= 18) middle cerebral artery occlusion (MCAO). Animals received either a bolus of 40 mg/kg ASA or saline as control 30 min after stroke onset. Permanent MCAO led to large infarct volumes with no differences between treatment with ASA (239.8 +/- 4.1 mm(3)) and saline (230.1 +/- 3.9 mm(3), p=0.15). In contrast, ASA therapy in temporary ischemia (87.2 +/- 6.2 mm(3)) reduced infarct size significantly compared to placebo (155.6 +/- 4.8 mm(3), p<0.0001). Only in temporary ischemia, ASA application reduced glutamate significantly at the time points 90, 120, and 150 min after MCAO. Pooled post-ischemic microdialysate concentrations of IL-6 in temporary MCAO were significantly higher after ASA treatment (215 +/- 81 pg/mL, p=0.0297) than in saline-treated rats (80 +/- 13 pg/mL). In the permanent MCAO group, no difference in IL-6 between the ASA (125 +/- 21 pg/mL) and saline group (68 +/- 34 pg/mL) was noted. No differences were seen for c-fos positive neurons in the penumbra and hippocampus between all groups. These results suggest that the neuroprotective effect of ASA is reflected by glutamate attenuation and IL-6 induction even if given after stroke onset, but only if reperfusion is achieved. (C) 2007 Elsevier Inc. All rights reserved.