Figure 1.

(A) Timeline of rabbit model TBM development. The first experimental model of rabbit TBM was established in 1923 using intra-cisternal inoculation of pathogenic mycobacteria. This model shows the presence of Mycobacteria in the meninges (Rich foci), disease progression with various infection/inoculum doses of different mycobacterial strains (chronic and subacute TBM) and the efficacy of anti-inflammatory drugs, such as thalidomide, on TBM. Since the TBM has a high mortality rate among children, a pediatric model of rabbit TBM was also developed and evaluated for disease progression in this population. Recent developments with the rabbit TBM model have introduced imaging techniques, such as PET scan (¹²⁴I-DPA-713), which is vital in understanding host-drug interactions during TBM treatment. (B) Disease presentation in rabbit model of TBM. The rabbit model of TBM have used different strains of pathogenic Mycobacterium, which demonstrated heterogeneity in the outcome of infection. High- and low-inoculum doses differ in their onset of disease symptoms and the rate of progression of infection. The laboratory Mtb strain H37Rv, clinical Mtb isolate HN878 and a high dose M. bovis Ravenal infection led to elevated cytokine response and severe inflammation of the meninges. These animals had early and robust disease pathology, accompanied by the presence of necrotizing granulomas and dissemination of Mtb to other organs of the body. In contrast, infection by Mtb CDC1551 and a low-dose M. bovis Ravenal, displayed a delayed and moderate-to-low inflammatory response without bacillary dissemination to other organs of the infected animals.