Lysophosphatidic acid (LPA) is a bioactive lysophospholipid that causes neuronal growth cones to collapse and neurites to retract through a RhoA-ROCK mediated pathway. It has been reported that the NSAID ibuprofen improves regeneration after spinal cord injury through a mechanism of inhibiting RhoA. This leads to the hypothesis that ibuprofen should block LPA-mediated growth cone collapse. We tested this hypothesis by treating embryonic chick retinal neurons with ibuprofen followed by LPA. Retinal growth cones collapsed with LPA in the presence of ibuprofen similar to control; however, growth cone collapse was effectively blocked by a ROCK inhibitor. Thus, our results do not support the designation of ibuprofen as a direct RhoA inhibitor.
