Departamento de Neuropatología, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Mexico City 14269, Mexico.
Red MEDICI, Carrera Médico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla 54090, Mexico.
Int J Mol Sci. 2022 Jun 9;23(12):6436. doi: 10.3390/ijms23126436.
Central nervous system (CNS) tuberculosis is the most lethal and devastating form among the diseases caused by . The mechanisms by which 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 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 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.
中枢神经系统（CNS）结核是由分枝杆菌引起的疾病中最致命和最具破坏性的形式。分枝杆菌进入中枢神经系统的机制仍不清楚。然而，血脑屏障和脉络丛被认为是进入大脑的可能途径。我们之前报道过某些结核分枝杆菌菌株具有在慢性进展性肺结核的小鼠模型中引起继发性中枢神经系统感染的增强能力。在这里，我们评估了中枢神经系统屏障的形态结构和分子完整性。为此，我们通过透射电子显微镜分析了来自感染两种分枝杆菌菌株的动物的脑实质微血管和脉络丛上皮的超微结构。此外，我们通过免疫技术测定了连接蛋白和细胞因子的表达。结果表明，存在结核分枝杆菌会导致脉络丛被破坏，但血脑屏障未被破坏，而且这种损伤的严重程度与菌株有关，这表明不同菌株引起中枢神经系统疾病的能力差异也可能与其直接或间接破坏这些屏障的能力有关。了解中枢神经系统结核中涉及的病理生理机制可能有助于建立新的生物标志物和治疗靶点。
