2-BFI ameliorates EAE-induced mouse spinal cord damage: effective therapeutic time window and possible mechanisms

Brain Res. 2012 Nov 5;1483:13-9. doi: 10.1016/j.brainres.2012.09.016. Epub 2012 Sep 14.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Benzofurans / therapeutic use*
  • Calcium-Binding Proteins / metabolism
  • Cytokines / metabolism
  • Disease Models, Animal
  • Encephalomyelitis, Autoimmune, Experimental / chemically induced
  • Encephalomyelitis, Autoimmune, Experimental / complications*
  • Enzyme-Linked Immunosorbent Assay
  • Freund's Adjuvant / toxicity
  • Imidazoles / therapeutic use*
  • Indoles
  • Mice
  • Mice, Inbred C57BL
  • Microfilament Proteins / metabolism
  • Myelin Sheath / pathology
  • Myelin-Oligodendrocyte Glycoprotein / toxicity
  • Nervous System Diseases / drug therapy
  • Nervous System Diseases / etiology
  • Peptide Fragments / toxicity
  • Spinal Cord Injuries / drug therapy*
  • Spinal Cord Injuries / etiology*
  • Spinal Cord Injuries / metabolism
  • Time Factors

Substances

  • Aif1 protein, mouse
  • Benzofurans
  • Calcium-Binding Proteins
  • Cytokines
  • Imidazoles
  • Indoles
  • Microfilament Proteins
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments
  • myelin oligodendrocyte glycoprotein (35-55)
  • Luxol Fast Blue MBS
  • 2-(2-benzofuranyl)-2-imidazoline
  • Freund's Adjuvant