Different concentrations (107, 105, 103 cfu/ml) of Candida albicans were injected intracisternally in rabbits. The highest inoculum was fatal within 14 h in all animals. In recipients of 105 and 103 cfu/ml inocula, the mean ± SD peak cerebrospinal fluid (CSF) tumor necrosis factor-α (TNFα) concentrations were 1.6 ± 2.42 and 0.3 ± 0.59 ng/ml, respectively, at 6 h; the mean ± SD CSF leukocyte and protein concentrations were 6291 ± 6515 and 453 ± 674 cells/mm3 (at 24 h) and 118 ± 90 and 109 ± 122 mg/dl (at 12 and 24 h), respectively. At 6-10 days after inoculation, a second peak of TNFα activity was accompanied by increased CSF inflammation. Mortality in the 105 and 103 cfu/ml inoculum groups was 56% and 22%, respectively. Fatal infection was associated with higher second CSF peak TNFα and leukocyte concentrations and a larger proportion of culture-positive CSF samples. Histopathology revealed hyphal invasion, vasculitis, abscesses, and acute and chronic inflammatory infiltration of meninges and brain parenchyma. This model can be useful for evaluation of the pathogenesis and therapy of central nervous system fungal infections.
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