{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:46:23Z","timestamp":1760150783225,"version":"build-2065373602"},"reference-count":34,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,12,30]],"date-time":"2023-12-30T00:00:00Z","timestamp":1703894400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"UNAM-PAPIIT","award":["IA205423"],"award-info":[{"award-number":["IA205423"]}]},{"name":"Instituto Nacional de Neurolog\u00eda y Neurocirug\u00eda Manuel Velasco Suarez","award":["IA205423"],"award-info":[{"award-number":["IA205423"]}]},{"name":"Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n","award":["IA205423"],"award-info":[{"award-number":["IA205423"]}]},{"name":"Instituto Polit\u00e9cnico Nacional","award":["IA205423"],"award-info":[{"award-number":["IA205423"]}]},{"name":"Programa de Posgrado Doctorado en Ciencias Quimicobiol\u00f3gicas and TheTuberculosis Research Commonwealth","award":["IA205423"],"award-info":[{"award-number":["IA205423"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Tuberculosis (TB) of the central nervous system (CNS) is a lethal and incapacitating disease. Several studies have been performed to understand the mechanism of bacterial arrival to CNS, however, it remains unclear. Although the interaction of the host, the pathogen, and the environment trigger the course of the disease, in TB the characteristics of these factors seem to be more relevant in the genesis of the clinical features of each patient. We previously tested three mycobacterial clinical isolates with distinctive genotypes obtained from the cerebrospinal fluid of patients with meningeal TB and showed that these strains disseminated extensively to the brain after intratracheal inoculation and pulmonary infection in BALB\/c mice. In this present study, BALB\/c mice were infected through the intranasal route. One of these strains reaches the olfactory bulb at the early stage of the infection and infects the brain before the lungs, but the histological study of the nasal mucosa did not show any alteration. This observation suggests that some mycobacteria strains can arrive directly at the brain, apparently toward the olfactory nerve after infecting the nasal mucosa, and guides us to study in more detail during mycobacteria infection the nasal mucosa, the associated connective tissue, and nervous structures of the cribriform plate, which connect the nasal cavity with the olfactory bulb.<\/jats:p>","DOI":"10.3390\/pathogens13010037","type":"journal-article","created":{"date-parts":[[2023,12,31]],"date-time":"2023-12-31T06:00:21Z","timestamp":1704002421000},"page":"37","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Central Nervous System Tuberculosis in a Murine Model: Neurotropic Strains or a New Pathway of Infection?"],"prefix":"10.3390","volume":"13","author":[{"given":"Daniel","family":"Rembao-Boj\u00f3rquez","sequence":"first","affiliation":[{"name":"Departamento de Neuropatolog\u00eda, Instituto Nacional de Neurolog\u00eda y Neurocirug\u00eda Manuel Velasco Su\u00e1rez, Insurgentes Sur 3877, Tlalpan, Ciudad de M\u00e9xico CP 14269, Mexico"},{"name":"Programa de Doctorado en Ciencias Quimicobiol\u00f3gicas, Escuela Nacional de Ciencias Biol\u00f3gicas, Instituto Polit\u00e9cnico Nacional, Prolongaci\u00f3n de Carpio y Plan de Ayala s\/n, Col. Santo Tom\u00e1s, Ciudad de M\u00e9xico C.P. 11340, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0637-5239","authenticated-orcid":false,"given":"Carlos","family":"S\u00e1nchez-Garibay","sequence":"additional","affiliation":[{"name":"Departamento de Neuropatolog\u00eda, Instituto Nacional de Neurolog\u00eda y Neurocirug\u00eda Manuel Velasco Su\u00e1rez, Insurgentes Sur 3877, Tlalpan, Ciudad de M\u00e9xico CP 14269, Mexico"},{"name":"Red MEDICI, Carrera M\u00e9dico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Tlalnepantla 54090, Mexico"},{"name":"Tuberculosis Research Commonwealth, Mexico City 14269, Mexico"},{"name":"Programa de Doctorado en Ciencias en Investigaci\u00f3n en Medicina, Escuela Superior de Medicina, Instituto Polit\u00e9cnico Nacional, Plan de San Luis y D\u00edaz Mir\u00f3n s\/n, Col. 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Health Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1128\/CMR.00042-07","article-title":"Central Nervous System Tuberculosis: Pathogenesis and Clinical Aspects","volume":"21","author":"Rock","year":"2008","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"94","DOI":"10.2174\/156652409787581655","article-title":"Pathogenesis of Central Nervous System Tuberculosis","volume":"9","author":"Be","year":"2009","journal-title":"Curr. Mol. Med. J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"321","DOI":"10.2174\/1871524911106040321","article-title":"Tuberculosis Infections of the Central Nervous System","volume":"11","author":"Bartzatt","year":"2012","journal-title":"Cent. Nerv. Syst. Agents Med. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.tcb.2005.03.009","article-title":"The Trojan Horse: Survival Tactics of Pathogenic Mycobacteria in Macrophages","volume":"15","author":"Nguyen","year":"2005","journal-title":"Trends Cell Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1212\/WNL.50.6.1827","article-title":"Tuberculosis Molecular Variation in CNS Infection Evidence for Strain-Dependent Neurovirulence","volume":"50","author":"Arvanitakis","year":"1998","journal-title":"Neurology"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Caws, M., Thwaites, G., Dunstan, S., Hawn, T.R., Lan, N.T.N., Thuong, N.T.T., Stepniewska, K., Huyen, M.N.T., Nguyen, D.B., and Tran, H.L. (2008). The Influence of Host and Bacterial Genotype on the Development of Disseminated Disease with Mycobacterium Tuberculosis. PLoS Pathog., 4.","DOI":"10.1371\/journal.ppat.1000034"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.tube.2010.05.002","article-title":"Specific Bacterial Genotypes of Mycobacterium Tuberculosis Cause Extensive Dissemination and Brain Infection in an Experimental Model","volume":"90","author":"Aguilar","year":"2010","journal-title":"Tuberculosis"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3934","DOI":"10.1128\/JCM.01181-06","article-title":"Beijing Genotype of Mycobacterium Tuberculosis Is Significantly Associated with Human Immunodeficiency Virus Infection and Multidrug Resistance in Cases of Tuberculous Meningitis","volume":"44","author":"Caws","year":"2006","journal-title":"J. Clin. Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.tube.2018.02.007","article-title":"Experimental Animal Models of Central Nervous System Tuberculosis: A Historical Review","volume":"110","year":"2018","journal-title":"Tuberculosis"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1038\/s41590-018-0119-x","article-title":"Tuberculous Meningitis: A Roadmap for Advancing Basic and Translational Research","volume":"19","author":"Jain","year":"2018","journal-title":"Nat. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.femsim.2005.01.002","article-title":"Detection of Mycobacterium Leprae in Nasal Mucosa Biopsies by the Polymerase Chain Reaction","volume":"44","author":"Goulart","year":"2005","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"177","DOI":"10.2500\/ajra.2009.23.3301","article-title":"Contribution of Nasal Biopsy to Leprosy Diagnosis","volume":"23","author":"Naves","year":"2009","journal-title":"Am. J. Rhinol. Allergy"},{"key":"ref_15","first-page":"579","article-title":"Nasal Mucosa Study of Leprosy Contacts with Positive Serology for the Phenolic Glycolipid 1 Antigen","volume":"76","author":"Miranda","year":"2010","journal-title":"Braz. J. Otorhinolaryngol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/S0092-8674(00)81927-3","article-title":"Neural Targeting of Mycobacterium Leprae Mediated by the G Domain of the Laminin-\u03b12 Chain","volume":"88","author":"Rambukkana","year":"1997","journal-title":"Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.1126\/science.282.5396.2076","article-title":"Role of A-Dystroglycan as a Schwann Cell Receptor for Mycobacterium Leprae","volume":"282","author":"Rambukkana","year":"1998","journal-title":"Science"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"9857","DOI":"10.1073\/pnas.96.17.9857","article-title":"A 21-KDa Surface Protein of Mycobacterium Leprae Binds Peripheral Nerve Laminin-2 and Mediates Schwann Cell Invasion","volume":"96","author":"Shimoji","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/S0092-8674(00)00142-2","article-title":"Role of the Cell Wall Phenolic Glycolipid-1 in the Peripheral Nerve Predilection of Mycobacterium Leprae","volume":"103","author":"Ng","year":"2000","journal-title":"Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.bbrc.2011.05.159","article-title":"Heparin-Binding Hemagglutinin HBHA from Mycobacterium Tuberculosis Affects Actin Polymerisation","volume":"410","author":"Esposito","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_21","first-page":"136","article-title":"Common Themes in Microbial Pathogenicity Revisited","volume":"61","author":"Finlay","year":"1997","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Skerry, C., Pokkali, S., Pinn, M., Be, N.A., Harper, J., Karakousis, P.C., and Jain, S.K. (2013). Vaccination with Recombinant Mycobacterium Tuberculosis PknD Attenuates Bacterial Dissemination to the Brain in Guinea Pigs. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0066310"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/j.tube.2011.07.003","article-title":"Strain-Dependent CNS Dissemination in Guinea Pigs after Mycobacterium Tuberculosis Aerosol Challenge","volume":"91","author":"Be","year":"2011","journal-title":"Tuberculosis"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.imbio.2017.11.002","article-title":"Regulatory T Cells: Friends or Foe in Human Mycobacterium Leprae Infection?","volume":"223","author":"Chaves","year":"2018","journal-title":"Immunobiology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/j.abd.2021.08.006","article-title":"Leprosy: Clinical and Immunopathological Characteristics","volume":"97","author":"Froes","year":"2022","journal-title":"An. Bras. Dermatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1111\/j.1574-695X.2002.tb00547.x","article-title":"Di\u00a1erential Microbial Clearance and Immunoresponse of Balb\/c (Nramp1 Susceptible) and DBA2 (Nramp1 Resistant) Mice Intracerebrally Infected with Mycobacterium Bovis BCG (BCG)","volume":"14","author":"Mazzolla","year":"2002","journal-title":"Immunol. Med. Microbiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1086\/511273","article-title":"A New Murine Model to Study the Pathogenesis of Tuberculous Meningitis","volume":"195","author":"Wieland","year":"2007","journal-title":"J. Infect. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Be, N.A., Bishai, W.R., and Jain, S.K. (2012). Role of Mycobacterium Tuberculosis PknD in the Pathogenesis of Central Nervous System Tuberculosis. BMC Microbiol., 12.","DOI":"10.1186\/1471-2180-12-7"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.1086\/592447","article-title":"Murine Model to Study the Invasion and Survival of Mycobacterium Tuberculosis in the Central Nervous System","volume":"198","author":"Be","year":"2008","journal-title":"J. Infect. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1046\/j.1365-2249.2003.02194.x","article-title":"Susceptibility to Tuberculosis-the Importance of the Pathogen as Well as the Host","volume":"133","author":"Mcshane","year":"2003","journal-title":"Clin. Exp. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.jneumeth.2012.02.015","article-title":"The Contribution of a Murine CNS-TB Model for the Understanding of the Host-Pathogen Interactions in the Formation of Granulomas","volume":"206","author":"Zucchi","year":"2012","journal-title":"J. Neurosci. Methods"},{"key":"ref_32","first-page":"27","article-title":"Chest Radiographic Findings in Neurotuberculosis without Pulmonary Signs and Symptoms","volume":"18","author":"Aurangzeb","year":"2008","journal-title":"J. Coll. Physicians Surg.-Pak."},{"key":"ref_33","first-page":"2770","article-title":"Tuberculous Meningitis Diagnosis and Treatment in Adults: A Series of 189 Suspected Cases","volume":"16","author":"Luo","year":"2018","journal-title":"Exp. Ther. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"17","DOI":"10.4103\/0976-3147.91925","article-title":"The Evaluation of the Clinical, Laboratory and the Radiological Findings of the Fifty-Five Cases Diagnosed with Tuberculous, Brucellar and Pyogenic Spondylodiscitis","volume":"3","author":"Yasar","year":"2012","journal-title":"J. Neurosci. Rural Pract."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/13\/1\/37\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:44:39Z","timestamp":1760132679000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/13\/1\/37"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,30]]},"references-count":34,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["pathogens13010037"],"URL":"https:\/\/doi.org\/10.3390\/pathogens13010037","relation":{},"ISSN":["2076-0817"],"issn-type":[{"type":"electronic","value":"2076-0817"}],"subject":[],"published":{"date-parts":[[2023,12,30]]}}}