TY - JOUR
T1 - Mycobacterium tuberculosis Infection Induces BCSFB Disruption but No BBB Disruption In Vivo
T2 - Implications in the Pathophysiology of Tuberculous Meningitis
AU - Sánchez-Garibay, Carlos
AU - Salinas-Lara, Citlaltepetl
AU - Gómez-López, Marcos Artemio
AU - Soto-Rojas, Luis O.
AU - Castillón-Benavides, Nidia Karen
AU - Castillón-Benavides, Omar Jorge
AU - Hernández-Campos, María Elena
AU - Hernández-Pando, Rogelio
AU - Marquina-Castillo, Brenda
AU - Flores-Barrada, Manuel Alejandro
AU - Choreño-Parra, José Alberto
AU - León-Contreras, Juan Carlos
AU - Tena-Suck, Martha Lilia
AU - Mata-Espinosa, Dulce Adriana
AU - Nava, Porfirio
AU - Medina-Mendoza, Jessica
AU - Rodríguez-Balderas, Cesar Augusto
N1 - Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/6/1
Y1 - 2022/6/1
N2 - 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.
AB - 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.
KW - blood-brain barrier
KW - blood-cerebrospinal fluid barrier
KW - central nervous system
KW - choroid plexus
KW - meningitis
KW - neuro-inflammation
KW - tuberculosis
UR - http://www.scopus.com/inward/record.url?scp=85131665926&partnerID=8YFLogxK
U2 - 10.3390/ijms23126436
DO - 10.3390/ijms23126436
M3 - Artículo
C2 - 35742886
AN - SCOPUS:85131665926
SN - 1661-6596
VL - 23
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 12
M1 - 6436
ER -