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The Role of Matrix Metalloproteinase 3 and 9 in the Pathogenesis of Acute Neuroinflammation. Implications for Disease Modifying Therapy

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Abstract

Matrix metalloproteinases (MMPs) are proteolytic enzymes that are involved in a variety of physiological and pathological processes, including those in CNS. In this study, plasma values of MMP-3 and MMP-9 have been compared in clinically isolated syndrome (CIS) and relapsing-remitting multiple sclerosis (RRMS) patients during their acute attacks, in relation to the biological activity of disease. Therefore, we compared the MMPs plasma values regarding Expanded Disability Status Scale (EDSS), progression index of disease (PID), acute brain lesion volume seen on magnetic resonance imaging (MRI) and index of blood-brain barrier (BBB) permeability destruction. The obtained results demonstrated higher plasma values of MMPs in both study groups than control values (p < 0.05). No statistical significances have been detected comparing the obtained values of both enzymes between CIS and RRMS group (p > 0.05). In both CIS and RRMS groups, the patients with higher EDSS showed higher MMPs plasma values (p < 0.05). The MMPs values were also significantly higher in both study patients with higher total number comparing to those with lower number of MRI brain lesion (p < 0.05) (beyond MMP-3 in RRMS). All obtained correlations, between MMPs and EDSS, PID, volume of MRI Gd-enhancement brain lesions, and index of BBB permeability, were positive (p < 0.05.) This study demonstrates alterations of both tested MMPs with closed correlation with the disease biological activity. Although MMPs are being implicated in the pathogenesis of acute neuroinflammation, the MMPs modulation might be useful in the future design of disease modifying therapy with the specific target profile.

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Acknowledgments

This work was supported by the grant from the scientific project number 41018 financed by the Ministry of Education and Science, Republic of Serbia. No conflict of interest exists for any of the authors listed in the article.

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Authors and Affiliations

  1. Clinic of Neurology, Clinical Center Nis, Bul. Dr Zorana Djindjica 48, 18000, Nis, Serbia

    Srdjan Ljubisavljevic, S. Vojinovic & G. Djordjevic

  2. Institute for Pathophysiology, Faculty of Medicine, University of Nis, Bul. Dr Zorana Djindjica 81, 18000, Nis, Serbia

    Srdjan Ljubisavljevic

  3. Institute for Biochemistry, Faculty of Medicine, University of Nis, Bul. Dr Zorana Djindjica 81, 18000, Nis, Serbia

    I. Stojanovic, J. Basic & D. Pavlovic

  4. Center for Radiology, Clinical Center Nis, Bul. Dr Zorana Djindjica 48, 18000, Nis, Serbia

    D. Stojanov

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  1. Srdjan Ljubisavljevic
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  2. I. Stojanovic
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  3. J. Basic
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  4. S. Vojinovic
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  5. D. Stojanov
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  6. G. Djordjevic
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  7. D. Pavlovic
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Correspondence to Srdjan Ljubisavljevic.

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Ljubisavljevic, S., Stojanovic, I., Basic, J. et al. The Role of Matrix Metalloproteinase 3 and 9 in the Pathogenesis of Acute Neuroinflammation. Implications for Disease Modifying Therapy. J Mol Neurosci 56, 840–847 (2015). https://doi.org/10.1007/s12031-015-0521-x

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  • DOI: https://doi.org/10.1007/s12031-015-0521-x

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