Mult Scler. 2004 Aug;10(4):376-80. Related Articles, Links
Decreased MMP-9 production in primary progressive multiple sclerosis patients.
Sastre-Garriga J, Comabella M, Brieva L, Rovira A, Tintore M, Montalban X.
Unitat de Neuroimmunologia Clinica, Hospital Vail d'Hebron, Barcelona, Espanya. firstname.lastname@example.org
BACKGROUND: An increase in MMP-9 levels has been found in relapsing-remitting (RR) multiple sclerosis (MS) showing correlation with magnetic resonance (MR) parameters mainly during relapses. However, data regarding primary progressive (PP) MS is scarce. OBJECTIVES: To determine both the pro and active forms of MMP-9 in PPMS and transitional progressive (TP) MS, RRMS and healthy controls (HC), and to assess the relationship between MMP-9 levels and clinical and radiological variables in PP/TPMS. METHODS: 73 patients with PP/TPMS, 50 RRMS and 43 HC were studied. Levels of pro and active forms of MMP-9 in serum were measured with ELISA. EDSS and MSFC scores were recorded and T2- and T1-weighted MR scans were obtained at the time of blood sampling and one and two years later for PP/TP MS cases. RESULTS: MMP-9 levels were 202.27 ng/ml for PP/TPMS, 242.20 ng/ml for RRMS and 274.49 ng/ml for HC. MMP-9 levels were significantly lower in PP/TPMS compared to RRMS (P= 0.026) and HC (P= 0.001). No significant correlations were found between MMP-9 levels and clinical scores or radiological parameters. CONCLUSIONS: These results point to different regulatory mechanisms of MMP-9 production and/or activity between PP/TPMS and RRMS.
PMID: 15327032 [PubMed - in process]
The Expression Profile Of Matrix MetalloProteinases (MMPs) And Their Inhibitors (TIMPs) In Lesions And Normal-Appearing White Matter Of Multiple Sclerosis
Raija L. P. Lindberg, Corline J. A. De Groot, Lisette Montagne, Peter Freitag, Paul van der Valk, Ludwig Kappos and David Leppert
Brain, Vol. 124, No. 9, 1743-1753, September 2001
University Hospitals, Departments of Research and Neurology, Basel, Switzerland and; University Hospital Vrije Universiteit, MS Centre for Research and Care, Division of NeuroPathology, Department of Pathology, The Netherlands
In Multiple Sclerosis, Matrix MetalloProteinases (MMPs) are effectors of crucial pathogenetic steps, such as Blood-Brain Barrier breakdown, invasion of Brain Parenchyma by Immune Cells and DeMyelination.
However, only limited data are available on the types of MMPs induced in the course of Multiple Sclerosis, and on the role of their endogenous antagonists, the Tissue Inhibitors of MetalloProteinases (TIMPs).
We quantified the transcriptional expression of six MMPs and the four TIMPs in lesions and in Normal-Appearing White Matter (NAWM) from post-mortem Multiple Sclerosis Brain tissue by real-time polymerase chain reaction, and compared levels with those in Brain tissue from six control patients without Neurological Disease.
The mRNA expression of MMP-7 and -9, but not of other MetalloProteinases [MMP-2 and -3, and Tumour Necrosis Factor-alpha (TNF-)-converting-enzyme] was equally upregulated throughout all stages of lesion formation with active inflammation, and in most of matched NAWM tissue.
The transcription of Cytokines TNF-/ß and InterLeukin-2 (IL-2), known modulators of MMPs, was upregulated only in distinct stages of lesion formation, while their receptors were not induced at all.
Which suggests that additional signalling molecules participate in the sustained upregulation of MMP-7 and -9 in Multiple Sclerosis. None of the TIMPs showed a significant induction over baseline expression of controls.
We hypothesize that an imbalance between MMP and TIMP expression may cause a persistent ProteoLytic overactivity in Multiple Sclerosis, that may be a factor for continuous tissue destruction, and hence for Secondary disease progression.
MMP-9 levels were 202.27 ng/ml for PP/TPMS, 242.20 ng/ml for RRMS and 274.49 ng/ml for HC
I'll just second Deb's comment that our 'discussion' on cognition vs intellect was a side issue, albeit a very important one and probably deserving of it's own thread. Of all the effects of MS cognitive decline is the one that scares me most!
We don't seem to get much or any input into these forum topics from MS researchers or so-called MS experts. I am wondering why
Users browsing this forum: No registered users