title: Title: role of matrix metalloproteinase -9 in progression of tuberculous meningitis: a pilot study in patients at different stages of the disease.
abstract: TBM (Tuberculous meningitis) is severe form of tuberculosis causing death of one third of the affected individuals or leaving two-third of the survivors disabled. MMP-9 (Matrix metalloproteinase-9) is produced by the central nervous system in a variety of inflammatory conditions and has a role in the breakdown of extracellular matrix and blood-brain barrier.
  
  
  
  In this study, the levels of MMP-9 and its inhibitor, TIMP-1 (tissue inhibitor of metalloproteinases-1), were screened using zymography and reverse zymography in cerebrospinal fluid and serum of tuberculous meningitis patients at different stages of the disease. Further, role of MMP-9 as therapeutic target was studied in C6 glioma cells infected with Mycobacterium tuberculosis H37Rv. Cells were treated with dexamethasone or SB-3CT (specific inhibitor of MMP-9) in combination with conventional antitubercular drugs.
  
  
  
  MMP-9 levels in patients were increased as the disease progressed to advanced stages. The infection led to increased MMP-9 levels in C6 glioma cells and specific inhibition of MMP-9 by SB-3CT augmented bacillary clearance when used along with antitubercular drugs.
  
  
  
  MMP-9 plays a prominent role in progression of tuberculous meningitis from initial to advanced stages. Increased levels of MMP-9 during advancement of the disease leads to degeneration of nervous tissue and blood brain barrier disruption. Hence, MMP-9 can be considered as a therapeutic target for efficient management of TBM and can be explored to inhibit further progression of the disease if used at an early stage.
authors.affiliation: Department of Biochemistry, Postgraduate Institute of Medical Education & Research, Chandigarh, 160012, India.
authors.forename: S
authors.initials: S
authors.lastname: Majeed
authors.affiliation: Department of Neurology, Postgraduate Institute of Medical Education & Research, Chandigarh, 160012, India.
authors.forename: P
authors.initials: P
authors.lastname: Singh
authors.affiliation: Department of Internal Medicine, Postgraduate Institute of Medical Education & Research, Chandigarh, 160012, India.
authors.forename: N
authors.initials: N
authors.lastname: Sharma
authors.affiliation: Department of Biochemistry, Postgraduate Institute of Medical Education & Research, Chandigarh, 160012, India. sadhnabiochem@gmail.com.
authors.forename: S
authors.initials: S
authors.lastname: Sharma
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000494:pharmacology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D003907:Dexamethasone / Q000494:pharmacology; D018450:Disease Progression; D005260:Female; D006573:Heterocyclic Compounds, 1-Ring / Q000494:pharmacology; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood* / Q000134:cerebrospinal fluid*; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology*; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000379:methods; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000472:pathogenicity; D010865:Pilot Projects; D013450:Sulfones / Q000494:pharmacology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood / Q000134:cerebrospinal fluid; D014390:Tuberculosis, Meningeal / Q000201:enzymology* / Q000503:physiopathology
chemical_list: D000995:Antitubercular Agents; D006573:Heterocyclic Compounds, 1-Ring; D061965:Matrix Metalloproteinase Inhibitors; C429533:SB 3CT compound; D013450:Sulfones; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D003907:Dexamethasone; D020780:Matrix Metalloproteinase 9
keywords: Antitubercular drugs; Inflammation; Matrixmetalloproteinase-9; Mycobacterium tuberculosis; SB-3CT; Tissue inhibitor of metalloproteinase-1; Tuberculous meningitis