Research Report2-BFI ameliorates EAE-induced mouse spinal cord damage: Effective therapeutic time window and possible mechanisms

Our previous studies showed that ligands to type 2 imidazoline receptors (I2R), including 2-(2-Benzofuranyl)-2-imidazoline (2-BFI) and Idazoxan, were effective in reducing spinal cord inflammation caused by experimental autoimmune encephalomyelitis (EAE). In the present study, we determined the effective therapeutic time window of 2-BFI and found that administration of 2-BFI in mice before the appearance of ascending flaccid paralysis (1-10 days post immunization), but not during the period when neurological deficits occurred (11-20 days post immunization), significantly ameliorated EAE-induced neurobehavioral deficits, reduced the infiltration of inflammatory cells into the spinal cord, and reduced the level of demyelination. More interestingly, giving 2-BFI during 1-10 days post immunization selectively suppressed IL-17 levels in the peripheral blood, which strongly suggests that IL-17 may be a good early marker to indicate EAE progression and that 2-BFI may target CD4+ T lymphocytes, especially Th17 cells to reduce IL-17 expression. Collectively, these studies led us to envisage that 2-BFI can be a useful drug to treat multiple sclerosis (MS) when used in combination with an early indicator of MS progression, such as IL-17.

► 2-BFI, a ligand to type 2 imidazoline receptor, is effective in reducing spinal cord inflammation caused by EAE. ► 2-BFI is effective when given before the appearance of ascending flaccid paralysis. ► 2-BFI inhibits IL-17 expression in the peripheral blood, which can be a companion early biomarker to indicate 2-BFI efficacy.