Protection of cortical neurons from excitotoxicity by conjugated linoleic acid

Conjugated linoleic acid (CLA) is an isomeric mixture of 18-carbon polyunsaturated fatty acids with conjugated double bonds derived from linoleic acid. CLA is sourced nutritionally from dairy products and ruminant animal meat and is associated with beneficial heath effects in several disorders, including cancer, atherosclerosis, diabetes, obesity, and inflammation. We investigated the potential for CLA to protect neurons from death in stroke simulated by exposing cultured mouse embryonic cortical neurons to glutamate. CLA (10 30 μM) significantly protected neuronal survival in response to glutamate (3 μM) excitotoxicity when given concurrently with glutamate. CLA (30 μM) also reduced neuron death when given up to 5 h after glutamate exposure (73.1 ± 13.3% protection, p < 0.01), suggesting potential utility as a post-injury therapeutic tool. The cis-9, trans-11 CLA isomer, which comprises about 40% of the commercial CLA mixture used, was identified as the active neuroprotective species. The other major species, trans-10, cis-12 CLA (40%) was without significant neuroprotective effect. CLA significantly increased neuronal Bcl-2 levels when given with glutamate and attenuated glutamate-induced dissipation of mitochondrial membrane potential, suggesting a stabilizing influence on mitochondrial function. These results show that CLA is capable of strong neuroprotective effects in glutamate excitotoxicity at concentrations likely achieved by consumption of CLA as a dietary supplement.