Mycobacterium tuberculosis Infection Induces BCSFB Disruption but No BBB Disruption In Vivo: Implications in the Pathophysiology of Tuberculous Meningitis

Carlos Sánchez-Garibay, Citlaltepetl Salinas-Lara, Marcos Artemio Gómez-López, Luis O. Soto-Rojas, Nidia Karen Castillón-Benavides, Omar Jorge Castillón-Benavides, María Elena Hernández-Campos, Rogelio Hernández-Pando, Brenda Marquina-Castillo, Manuel Alejandro Flores-Barrada, José Alberto Choreño-Parra, Juan Carlos León-Contreras, Martha Lilia Tena-Suck, Dulce Adriana Mata-Espinosa, Porfirio Nava, Jessica Medina-Mendoza, Cesar Augusto Rodríguez-Balderas

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Central nervous system (CNS) tuberculosis is the most lethal and devastating form among the diseases caused by Mycobacterium tuberculosis. The mechanisms by which M. tuberculosis bacilli enter the CNS are still unclear. However, the BBB and the BCSFB have been proposed as possible routes of access into the brain. We previously reported that certain strains of M. tuberculosis possess an enhanced ability to cause secondary CNS infection in a mouse model of progressive pulmonary tuberculosis. Here, we evaluated the morphostructural and molecular integrity of CNS barriers. For this purpose, we analyzed through transmission electron microscopy the ultrastructure of brain parenchymal microvessels and choroid plexus epithelium from animals infected with two mycobacterial strains. Additionally, we determined the expression of junctional proteins and cytokines by immunological techniques. The results showed that the presence of M. tuberculosis induced disruption of the BCSFB but no disruption of the BBB, and that the severity of such damage was related to the strain used, suggesting that variations in the ability to cause CNS disease among distinct strains of bacteria may also be linked to their capacity to cause direct or indirect disruption of these barriers. Understanding the pathophysiological mechanisms involved in CNS tuberculosis may facilitate the establishment of new biomarkers and therapeutic targets.

Original languageEnglish
Article number6436
JournalInternational Journal of Molecular Sciences
Volume23
Issue number12
DOIs
StatePublished - 1 Jun 2022

Keywords

  • blood-brain barrier
  • blood-cerebrospinal fluid barrier
  • central nervous system
  • choroid plexus
  • meningitis
  • neuro-inflammation
  • tuberculosis

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