Arachidonic acid-induced oxidative injury to cultured spinal cord neurons

Spinal cord trauma can cause a marked release of free fatty acids, in parti cular, arachidonic acid (AA), from cell membranes, Free fatty acids, and AA by itself, may lead to secondary damage to spinal cord neurons. To study t his hypothesis, cultured spinal cord neurons were exposed to increasing con centrations of AA (0.01-10 mu M). AA-induced injury to spinal cord neurons was assessed by measurements of cellular oxidative stress, intracellular ca lcium levels, activation of nuclear factor-kappa B (NF-kappa B), and cell v iability. AA treatment increased intracellular calcium concentrations and d ecreased cell viability, Oxidative stress increased significantly in neuron s exposed to 1 and 10 mu M AA, In addition, AA treatment activated NF-kappa B and decreased levels of the inhibitory subunit, I kappa B, It is interes ting that manganese superoxide dismutase protein levels and levels of intra cellular total glutathione increased in neurons exposed to this fatty acid for 24 h, consistent with a compensatory response to increased oxidative st ress. These results strongly support the hypothesis that free fatty acids c ontribute to the tissue injury observed following spinal cord trauma.