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 mm3) and saline (230.1+/-3.9 mm3, p=0.15). In contrast, ASA therapy in temporary ischemia (87.2+/-6.2 mm3) reduced infarct size significantly compared to placebo (155.6+/-4.8 mm3, 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.
Berger
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Department of Neurology, University of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany. christian.berger@urz.uni-heidelberg.de
Stauder
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A
Xia
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F
Sommer
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C
Schwab
S
S
D000704:Analysis of Variance; D000818:Animals; D001241:Aspirin / Q000627:therapeutic use*; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D002544:Cerebral Infarction / Q000209:etiology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects; D018698:Glutamic Acid / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000150:complications* / Q000188:drug therapy; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009195:Peroxidase / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D015850:Interleukin-6; D018696:Neuroprotective Agents; D016760:Proto-Oncogene Proteins c-fos; D018698:Glutamic Acid; D009195:Peroxidase; D001241:Aspirin