The first attempts to enhance remyelination using growth factors stemmed from the work on IGF-I expression in the cuprizone, cryogenic and EAE models, and involved daily intravenous or sub-cutaneous delivery of IGF-I after induction of EAE by passive transfer of MBP-reactive T-lymphocytes in Lewis rats (Yao et al., 1995a (Yao et al., , 1996 .