Inhibition of cyclooxygenase‐2 protects motor neurons in an organotypic model of amyotrophic lateral sclerosis

The pathogenesis of motor neuron loss in amyotrophic lateral sclerosis (ALS) is thought to involve both glutamate‐mediated excitotoxicity and oxidative damage due to the accumulation of free radicals and other toxic molecules. Cyclooxygenase‐2 (COX‐2) may play a key role in these processes by producing prostaglandins, which trigger astrocytic glutamate release, and by inducing free radical formation. We tested the effects of COX‐2 inhibition in an organotypic spinal cord culture model of ALS. The COX‐2 inhibitor (SC236) provided significant protection against loss of spinal motor neurons in this system, suggesting that it may be useful in the treatment of ALS. Ann Neurol 2000;48:792–795

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