Disruption of the Blood–CSF Barrier in Tuberculous and Non-Tuberculous Meningitis: Mechanisms, Diagnosis, and Clinical Impact

Abstract

The blood–cerebrospinal fluid barrier (BCSFB) is an important interface in the central nervous system (CNS), controlling immune surveillance, waste removal, and pathogen invasion. Breakdown of the BCSFB is a characteristic of meningitis, such as tuberculous meningitis (TBM) and non-tuberculous meningitis (non-TBM), due to bacterial, viral, fungal, or parasitic infection. This review examines the physiology and function of the BCSFB, its contribution to CNS homeostasis, and the mechanisms with which neurotropic pathogens violate the barrier to cause meningitis. We explain the differential pathophysiological profiles of TBM, including granulomatous inflammation, and non-TBM, having purulent or lymphocytic reactions, and their corresponding cerebrospinal fluid (CSF) profiles. Diagnostic issues are discussed, pointing out novel biomarker-based methods, like CSF metabolomics, to distinguish TBM from non-TBM. Clinical implication of the disruption of BCSFB, such as neuroinflammation, neuronal dysfunction, and elevated mortality, is assessed, stressing the necessity for more effective diagnostic and therapeutic interventions in order to reduce the global burden of meningitis.