Journal of Clinical Microbiology and Antimicrobials
Open Access

Abstract

MMP-9 the prominent mediator of neurological damage in tuberculous meningitis

Shahnawaz Majeed

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[1]. The main cause of disabilities and death is the neurological destruction mainly caused by immense inflammatory response.[2] 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. [3].Moreover, the correlation between tuberculosis infection and MMP-9 is an earlier known fact.[4, 5]   Methodology & Theoretical Orientation: This study was designed to evaluate the role of MMP-9 in advancement of TBM and therapeutic role of targeting MMP-9 against TBM. 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 and mouse model of TBM infected with Mycobacterium tuberculosis H37Rv. Infected cells and mice were treated with dexamethasone or SB-3CT (specific inhibitor of MMP-9) in combination with conventional antitubercular drugs. Findings: MMP-9 levels in patients were increased as the disease progressed to advanced stages. The infection lead to increased MMP-9 levels in C6 glioma cells and mice. The specific inhibition of MMP-9 by SB-3CT augmented bacillary clearance when used along with antitubercular drugs in both infected C6 glioma cells and mice model of TBM.