CSF infusion of TrkB agonist, 7,8-dihydroxyflavone, is ineffective in promoting remyelination in cuprizone and EAE models of multiple sclerosis

Abstract

Small molecular weight functional mimetics of brain-derived neurotrophic factor (BDNF) which act via the TrkB receptor have been developed to overcome the pharmacokinetic limitations of BDNF as a therapeutic for neurological disease. Activation of TrkB on oligodendrocytes has been identified as a potential strategy for myelin repair in demyelinating conditions. Here, we tested the efficacy of intracerebroventricular infusion of TrkB agonist 7,8-dihydroxyflavone (DHF) to promote myelin repair in the cuprizone model and alter the course of experimental autoimmune encephalomyelitis (EAE). In these two distinct mouse models used for the preclinical testing of remyelinating therapeutics, we found..