Mechanisms of the neuroprotective effect of aspirin after oxygen and glucose deprivation in rat forebrain slices.
Acetylsalicylic acid (ASA, Aspirin) is an anti-inflammatory drug with a wide spectrum of pharmacological activities and multiple sites of action. Apart from its preventive actions against stroke due to its antithrombotic properties, recent data in the literature suggest that high concentrations of ASA also exert direct neuroprotective effects. We have used an in vitro model of brain ischaemia using rat forebrain slices deprived of oxygen and glucose to test ASA neuroprotective properties. We have found that ASA inhibits neuronal damage at concentrations lower than those previously reported (0.1-0.5 mM), and that these effects correlate with the inhibition of excitatory amino acid release, of NF-kappaB translocation to the nucleus and iNOS expression caused by ASA. All of these three mechanisms may mediate the neuroprotective effects of this drug. Our results also show that the effects of ASA are independent of COX inhibition. Taken together, our present findings show that ASA is neuroprotective in an in vitro model of brain ischaemia at doses close to those recommended for its antithrombotic effects.
Moro
M A
MA
Departamento de Farmacología, Facultad de Medicina, Universidad Complutense de Madrid (UCM), 28040, Madrid, Spain. nlfucm@eucmax.sim.ucm.es
De Alba
J
J
Cárdenas
A
A
De Cristóbal
J
J
Leza
J C
JC
Lizasoain
I
I
Díaz-Guerra
M J
MJ
Boscá
L
L
Lorenzo
P
P
D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D015153:Blotting, Western; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D004586:Electrophoresis; D018846:Excitatory Amino Acids / Q000378:metabolism; D005947:Glucose / Q000172:deficiency*; D000860:Hypoxia / Q000473:pathology*; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018846:Excitatory Amino Acids; D016328:NF-kappa B; D018696:Neuroprotective Agents; D009569:Nitric Oxide; D007770:L-Lactate Dehydrogenase; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D010751:Phosphopyruvate Hydratase; D005947:Glucose; D001241:Aspirin