Brain protection conferred by long-term administration of 2-(2-benzofuranyl)-2-imidazoline against experimental autoimmune encephalomyelitis.

ABSTRACT

Our previous studies showed that 2-(2-benzofuranyl)-2-imidazoline (2-BFI), a ligand to type 2 imidazoline receptor, was protective against brain and spinal cord injury caused by experimental autoimmune encephalomyelitis (EAE). In the present study, we investigated the effect of long-term administration of 2-BFI and the dose-dependent response relationship of long-term administration of 2-BFI with neuroprotection. Treatment with 2-BFI at doses of 5, 10, and 20 mg/kg for 14 days significantly reduced hind limb paralysis and the severity of EAE compared with the EAE control group. Long-term use of 2-BFI was not only safe to mice, but also dose-dependently reduced the expression of inflammatory cytokines, including TNF-α, Interferon-γ and Interleukin-17A, compared with the EAE control group. Expressions of neuronal injury markers, including cytochrome c, AIF and ß-APP, were also reduced significantly in response to long-term 2-BFI treatment. Together, these results provided new evidence to demonstrate that 2-BFI is a safe and effective candidate for further development as a therapeutic drug for treatment of multiple sclerosis.