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

Central nervous system (CNS) tuberculosis is the most lethal and devastating form among the diseases caused by <i>Mycobacterium tuberculosis</i>. The mechanisms by which <i>M. tuberculosis</i> bacilli enter the CNS are still unclear. However, the BBB and the BCSFB have been p...

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Main Authors: 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
Format: Article
Language:English
Published: MDPI AG 2022-06-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/12/6436
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author 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
author_facet 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
author_sort Carlos Sánchez-Garibay
collection DOAJ
description Central nervous system (CNS) tuberculosis is the most lethal and devastating form among the diseases caused by <i>Mycobacterium tuberculosis</i>. The mechanisms by which <i>M. tuberculosis</i> 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 <i>M. tuberculosis</i> 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 <i>M. tuberculosis</i> 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.
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spelling doaj.art-367c1d0eaa3241458989353a9214db352023-11-23T17:00:48ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-06-012312643610.3390/ijms23126436<i>Mycobacterium tuberculosis</i> Infection Induces BCSFB Disruption but No BBB Disruption In Vivo: Implications in the Pathophysiology of Tuberculous MeningitisCarlos Sánchez-Garibay0Citlaltepetl Salinas-Lara1Marcos Artemio Gómez-López2Luis O. Soto-Rojas3Nidia Karen Castillón-Benavides4Omar Jorge Castillón-Benavides5María Elena Hernández-Campos6Rogelio Hernández-Pando7Brenda Marquina-Castillo8Manuel Alejandro Flores-Barrada9José Alberto Choreño-Parra10Juan Carlos León-Contreras11Martha Lilia Tena-Suck12Dulce Adriana Mata-Espinosa13Porfirio Nava14Jessica Medina-Mendoza15Cesar Augusto Rodríguez-Balderas16Departamento de Neuropatología, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Mexico City 14269, MexicoDepartamento de Neuropatología, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Mexico City 14269, MexicoInstituto Nacional de Rehabilitación (INR), “Luis Guillermo Ibarra Ibarra”, Mexico City 14389, MexicoRed MEDICI, Carrera Médico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla 54090, MexicoUnidad de Especialidades Médicas de la Secretaria de la Defensa Nacional, Mexico City 11200, MexicoNeurological Center, American British Cowdry Hospital, Mexico City 05330, MexicoSección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Casco de Santo Tomás, Mexico City 11340, MexicoExperimental Pathology Section, Department of Pathology, National Institute of Medical Science and Nutrition “Salvador Zubirán”, Mexico City 14080, MexicoDepartment of Pathology, National Institute of Medical Science and Nutrition “Salvador Zubirán”, Mexico City 14080, MexicoDivisión Académica Multidisciplinaria de Comalcalco de la Universidad Juárez Autónoma de Tabasco, Comalcalco 86658, MexicoRed MEDICI, Carrera Médico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla 54090, MexicoLaboratorio de Microscopia Electrónica, Departamento de Patología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, MexicoDepartamento de Neuropatología, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Mexico City 14269, MexicoExperimental Pathology Section, Department of Pathology, National Institute of Medical Science and Nutrition “Salvador Zubirán”, Mexico City 14080, MexicoDepartment of Physiology, Biophysics and Neuroscience, Mexico City 07360, MexicoRed MEDICI, Carrera Médico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla 54090, MexicoDepartamento de Bioterio, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Mexico City 14269, MexicoCentral nervous system (CNS) tuberculosis is the most lethal and devastating form among the diseases caused by <i>Mycobacterium tuberculosis</i>. The mechanisms by which <i>M. tuberculosis</i> 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 <i>M. tuberculosis</i> 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 <i>M. tuberculosis</i> 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.https://www.mdpi.com/1422-0067/23/12/6436tuberculosiscentral nervous systemmeningitisblood-brain barrierblood-cerebrospinal fluid barrierchoroid plexus
spellingShingle 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
<i>Mycobacterium tuberculosis</i> Infection Induces BCSFB Disruption but No BBB Disruption In Vivo: Implications in the Pathophysiology of Tuberculous Meningitis
International Journal of Molecular Sciences
tuberculosis
central nervous system
meningitis
blood-brain barrier
blood-cerebrospinal fluid barrier
choroid plexus
title <i>Mycobacterium tuberculosis</i> Infection Induces BCSFB Disruption but No BBB Disruption In Vivo: Implications in the Pathophysiology of Tuberculous Meningitis
title_full <i>Mycobacterium tuberculosis</i> Infection Induces BCSFB Disruption but No BBB Disruption In Vivo: Implications in the Pathophysiology of Tuberculous Meningitis
title_fullStr <i>Mycobacterium tuberculosis</i> Infection Induces BCSFB Disruption but No BBB Disruption In Vivo: Implications in the Pathophysiology of Tuberculous Meningitis
title_full_unstemmed <i>Mycobacterium tuberculosis</i> Infection Induces BCSFB Disruption but No BBB Disruption In Vivo: Implications in the Pathophysiology of Tuberculous Meningitis
title_short <i>Mycobacterium tuberculosis</i> Infection Induces BCSFB Disruption but No BBB Disruption In Vivo: Implications in the Pathophysiology of Tuberculous Meningitis
title_sort i mycobacterium tuberculosis i infection induces bcsfb disruption but no bbb disruption in vivo implications in the pathophysiology of tuberculous meningitis
topic tuberculosis
central nervous system
meningitis
blood-brain barrier
blood-cerebrospinal fluid barrier
choroid plexus
url https://www.mdpi.com/1422-0067/23/12/6436
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