title: Adjunctive role of MMP-9 inhibition along with conventional anti-tubercular drugs against experimental tuberculous meningitis.
abstract: Tuberculous meningitis (TBM) is an outcome of neuroinflammatory degeneration caused due to Mycobacterium tuberculosis infection and leads to death or neurological disabilities in the affected individuals. It causes the highest morbidity and mortality amongst all forms of tuberculosis. Matrix metalloproteinase-9 levels increase and cause inflammatory destruction during progression of the disease. Although corticosteroids are usually given as an adjuvant therapy to overcome these complications, treatment outcome is contradictory. This study was designed to evaluate whether specific inhibition of MMP-9 can be beneficial in management of the disease. MMP-9 levels were inhibited using SB-3CT or dexamethasone along with conventional drugs for treatment of tuberculous meningitis. Both SB-3CT and dexamethasone decreased the elevated levels of MMP-9 in sera and tissues of the infected mice. However, dexamethasone administration had an inhibitory effect on bacillary clearance, while SB-3CT potentiated the bacillary clearance, suggesting that MMP-9, if specifically inhibited, can be beneficial in the management of TBM.
authors.affiliation: Department of Biochemistry, Postgraduate Institute of Medical Education & Research, Chandigarh, India.
authors.forename: Shahnawaz
authors.initials: S
authors.lastname: Majeed
authors.affiliation: Department of Histopathology, Postgraduate Institute of Medical Education & Research, Chandigarh, India.
authors.forename: Bishan D
authors.initials: BD
authors.lastname: Radotra
authors.affiliation: Department of Biochemistry, Postgraduate Institute of Medical Education & Research, Chandigarh, India.
authors.forename: Sadhna
authors.initials: S
authors.lastname: Sharma
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D004357:Drug Synergism; D006573:Heterocyclic Compounds, 1-Ring / Q000494:pharmacology*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000302:isolation & purification; D011480:Protease Inhibitors / Q000494:pharmacology*; D013450:Sulfones / Q000494:pharmacology*; D014390:Tuberculosis, Meningeal / Q000378:metabolism* / Q000473:pathology*
chemical_list: D000995:Antitubercular Agents; D006573:Heterocyclic Compounds, 1-Ring; D011480:Protease Inhibitors; C429533:SB 3CT compound; D013450:Sulfones; D003907:Dexamethasone; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse
keywords: Mycobacterium tuberculosis; SB-3CT; inflammation; matrix metalloproteinase-9; tuberculous meningitis