Experimental autoimmune encephalomyelitis were induced into C57/B6 mice as previously described (9). All procedures involving animals were performed according to the animal protocol guidelines prescribed by the Institutional Animal Care and Use Committee authorization no. 643 at San Raffaele Scientific Institute (Milan, Italy). Imipramine (20 mg kg−1, Sigma) was injected into the peritoneum on the day of clinical onset; control mice were injected with the saline solution in which imipramine was dissolved. Injections were repeated every day and mice were weighed and scored for clinical signs daily up to the day of culling. Clinical assessment of EAE was performed according to the following scoring criteria: 0 = healthy; 1 = limp tail; 2 = ataxia and/or paresis of hindlimbs; 3 = paralysis of hindlimbs and/or paresis of forelimbs; 4 = tetraparalysis; and 5 = moribund or death.