Tsenova L, Sokol K, Freedman V H, Kaplan G
Laboratory of Cellular Physiology and Immunology, Laboratory Animal Research Center, Rockefeller University, New York, New York 10021, USA.
J Infect Dis. 1998 Jun;177(6):1563-72. doi: 10.1086/515327.
Tuberculous meningitis (TBM) is a devastating form of tuberculosis that occurs predominantly in children and in immunocompromised adults. To study the pathogenesis of TBM, a rabbit model of acute mycobacterial central nervous system infection was set up (8-day study). Inoculation of live Mycobacterium bovis Ravenel intracisternally induced leukocytosis (predominantly mononuclear cells), high protein levels, and release of tumor necrosis factor-alpha (TNF-alpha) into the cerebrospinal fluid within 1 day. Histologically, severe meningitis with thickening of the leptomeninges, prominent vasculitis, and encephalitis was apparent, and mortality was 75% by day 8. In animals treated with antituberculous antibiotics only, the inflammation and lesions of the brain persisted despite a decrease in mycobacteria; 50% of the rabbits died. When thalidomide treatment was combined with antibiotics, there was a marked reduction in TNF-alpha levels, leukocytosis, and brain pathology. With this combination treatment, 100% of the infected rabbits survived, suggesting a potential clinical use for thalidomide in TBM.
结核性脑膜炎（TBM）是一种严重的结核病形式，主要发生在儿童和免疫功能低下的成年人中。为了研究TBM的发病机制，建立了一种急性分枝杆菌中枢神经系统感染的兔模型（为期8天的研究）。脑池内接种活的牛分枝杆菌Ravenel在1天内诱导白细胞增多（主要是单核细胞）、高蛋白水平以及肿瘤坏死因子-α（TNF-α）释放到脑脊液中。组织学上，可见严重的脑膜炎，伴有软脑膜增厚、明显的血管炎和脑炎，到第8天死亡率为75%。仅用抗结核抗生素治疗的动物，尽管分枝杆菌数量减少，但脑内的炎症和病变仍持续存在；50%的兔子死亡。当沙利度胺治疗与抗生素联合使用时，TNF-α水平、白细胞增多和脑病理学有明显降低。采用这种联合治疗，100%的感染兔子存活，这表明沙利度胺在TBM中具有潜在的临床应用价值。
