Neurochemical Research

, Volume 40, Issue 8, pp 1719–1727 | Cite as

The Use of Agmatine Provides the New Insight in an Experimental Model of Multiple Sclerosis

  • Milica Ninkovic
  • Ivana Stevanovic
  • Ivana Stojanovic
  • Srdjan Ljubisavljevic
  • Jelena Basic
  • Predrag Peric
Original Paper
First Online:
Received:
Revised:
Accepted:

Abstract

The aim of the study is to investigate the hypothesis that agmatine (AGM) enhances blood brain barrier (BBB) compounds properties in experimental autoimmune encephalomyelitis (EAE), which is an established animal model for studying multiple sclerosis (MS). Wild-type (WT) and knockout (KO) CBA/H iNOS−/− mice, 3 months old (15 ± 5 g) were used for EAE induction by myelin basic protein (MBP) dissolved in complete Freund’s adjuvant (CFA). The animals were divided into control, CFA, EAE, EAE + AGM and AGM groups. After the development of full clinical remission, the animals were sacrificed and the immunohistochemical and biochemical examinations were performed in brain homogenates. We had noticed the increased expressions of occludin in WT and KO mice with EAE + AGM, compared to EAE groups in which these expressions were significantly decreased compared to the controls. The significant elevations of matrix metalloproteinases (MMPs)—MMP-3 and MMP-9 in WT and KO EAE animals were decreased during AGM treatment in both groups. AGM application post EAE in WT and KO mice caused decreased level of Iba-1 stain, compared to EAE groups. The obtained results suggest beneficial AGM effects in EAE on BBB components, which might be useful for novel therapeutic strategies in MS.

Keywords

Experimental autoimmune encephalomyelitis Agmatine Occludin Microglia Matrix metalloproteinases 
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Notes

Acknowledgments

This work was supported by a Grant from Scientific Project Number 41018 financed by the Ministry of Education and Science, Republic of Serbia.

Conflict of interest

None.

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Milica Ninkovic
    • 1
  • Ivana Stevanovic
    • 1
  • Ivana Stojanovic
    • 2
  • Srdjan Ljubisavljevic
    • 3
    • 4
  • Jelena Basic
    • 1
  • Predrag Peric
    • 5
  1. 1.Institute for Medical ResearchMilitary Medical AcademyBelgradeSerbia
  2. 2.Faculty of Medicine, Institute for BiochemistryUniversity of NisNisSerbia
  3. 3.Clinic for NeurologyClinical Centre of NisNisSerbia
  4. 4.Faculty of Medicine, Institute for PathophysiologyUniversity of NisNisSerbia
  5. 5.Clinic of NeurosurgeryMilitary Medical AcademyBelgradeSerbia

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