Aspirin Soothes Overexcited Rat Nerves

Aspirin appears to protect against damage to rat nerve cells inflicted by the amino acid glutamate, which has been implicated in some chronic degenerative diseases. But some experts are skeptical about whether the test-tube findings, reported in today's issue of Science, are relevant to humans.

Glutamate transmits messages in the brain. But at high concentrations, it becomes a potent excitotoxin that kills brain cells. Scientists have uncovered evidence in the past few years that glutamate's toxic effects may play a role in nerve-cell death seen in chronic neurodegenerative diseases such as Huntington's and amyotrophic lateral sclerosis, or Lou Gehrig's Disease.

Knowing that neurodegeneration often accompanies inflammation, and that aspirin dampens the inflammatory response, pharmacologist Mariagrazia Grilli and colleagues at the University of Brescia Medical School in Italy set out to see if aspirin could prevent neurodegeneration. They exposed rat brain cells to toxic glutamate levels and either a cocktail of aspirin and its metabolite sodium salicylate, or a second anti-inflammatory drug, indomethacin. Only the aspirin cocktail, at concentrations equivalent to those in people who take aspirin, protected against glutamate toxicity.

Grilli's team traced aspirin's protective effects to its ability to inhibit glutamate's activation of two proteins--nuclear factor kappa B and Rel. The proteins are transcription factors that switch on genes involved in immune function and the inflammatory response. But it's unclear how damping the transcription factors thwarts neurotoxicity.

By no means do the findings suggest that aspirin wards off Huntington's or other chronic neurodegenerative diseases, says a drug company scientist who requested anonymity. The scientist, who is developing aspirin substitutes, says that the popular painkiller has manifold effects in cell culture at concentrations used in the study. "Aspirin has been on the market for a hundred years," he says. "I think we would have seen this before." Nevertheless, says Johns Hopkins University glutamate researcher Jeffrey Rothstein, the findings "sound really intriguing" and should be followed up.

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