Ferulic acid modulates nitric oxide synthase expression in focal cerebral ischemia

Nitric oxide (NO) is generated by three different NO synthase (NOS) isoforms, endothelial NOS (eNOS), inducible NOS (iNOS), and neuronal NOS (nNOS). It is known that eNOS produces NO, which exerts a protective effect, while iNOS produces NO with neurotoxic effects. Ferulic acid preserves neuronal cells against from cerebral ischemia and glutamate-induced excitotoxicity. This study confirmed the neuroprotective effect of ferulic acid and investigated the levels of three NOS isoforms in focal cerebral ischemia with or without ferulic acid. Rats were immediately treated with ferulic acid (100 mg/kg, i.v.) after middle cerebral artery occlusion (MCAO). Brains tissues were collected at 24 h after the onset of occlusion. The expressions of these three isoforms in cerebral ischemia with ferulic acid were analyzed using Western blot technique. Ferulic acid treatment significantly decreases the number of TUNEL-positive cells in the cerebral cortex against MCAO injury. The levels of eNOS decreased in MCAO-operated animals, while ferulic acid treatment attenuated the MCAO-induced decrease of eNOS. However, iNOS and nNOS expression levels increased during MCAO, and ferulic acid prevented injury-induced increase of these isoforms. Thus, these findings suggest that the up- and down modulation of three isoforms by ferulic acid is associated with a neuroprotective mechanism.