Neuroprotection by aspirin and sodium salicylate through blockade of NF-kappaB activation.
Aspirin (acetylsalicylic acid) is a commonly prescribed drug with a wide pharmacological spectrum. At concentrations compatible with amounts in plasma during chronic anti-inflammatory therapy, acetylsalicylic acid and its metabolite sodium salicylate were found to be protective against neurotoxicity elicited by the excitatory amino acid glutamate in rat primary neuronal cultures and hippocampal slices. The site of action of the drugs appeared to be downstream of glutamate receptors and to involve specific inhibition of glutamate-mediated induction of nuclear factor kappa B. These results may contribute to the emerging theme of anti-inflammatory drugs and neurodegeneration.
Grilli
M
M
Division of Pharmacology, Department of Biomedical Sciences and Biotechnologies, University of Brescia Medical School, Brescia, I-25123 Italy. mpharm@master.cci.unibs.it
Pizzi
M
M
Memo
M
M
Spano
P
P
D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018698:Glutamic Acid / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D016202:N-Methylaspartate / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017966:Pyramidal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012980:Sodium Salicylate / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D015854:Up-Regulation
D016328:NF-kappa B; D018696:Neuroprotective Agents; D018808:Transcription Factor AP-1; D018698:Glutamic Acid; D016202:N-Methylaspartate; D001241:Aspirin; D002118:Calcium; D012980:Sodium Salicylate