Morphological Changes in the Brain of Mice with Systemic Candidiasis Treated with Composition of Amphotericin B and Oxidized Dextran

Abstract

We observed morphological manifestation of encephalitis 3, 7, 10 and 28 days after intravenous infection of adult male CBA mice with Candida albicans. Compounds were administered intraperitoneally every other day starting from the next day postinfection. Untreated animals (100%) died over the period between days 18 and 20 postinfection; 60% animals receiving oxidized dextran alone survived by day 28 of observation. All animals treated with amphotericin B and composition of amphotericin B and oxidized dextran survived. On day 3 postinfection, the count of macrophage infiltrates and granulomas in the cerebral interstitium of mice treated with amphotericin B was equal to that in untreated mice, but was sufficiently lower in animals treated with the composition or oxidized dextran alone. On day 10, this index was similar in all groups and was approximately 5 times lower than in untreated animals on day 3. On day 28, macrophage infiltrates and granulomas were absent in the brain of all treated mice. These data suggest that oxidized dextran produced a therapeutic effect, which manifested earlier than the effect of amphotericin B and potentiated its effect, probably due to its competition with Candida albicans for mannose receptors on the brain-blood barrier endothelium.

Targeting the C-type Lectins-Mediated Host-Pathogen Interactions with Dextran

“…Targeting the MR is suggested for vaccine development (201), for delivery of cargo into macrophages (202) or liver cells (195). Dextran can play a role in the prevention of pathogen binding, entry and signaling in MR-expressing myeloid cells wich participate in blood-brain barrier disruption in neuroinvasive infections (208): this was probably the case in prevention of C. albicans infection in the brain (168). Skewing the T helper responses could be a mechanism that allowed dextran derivatives to decrease tissue remodelling in the BCG infection model (159, 166) (Figure 4).…”

“…In a model of systemic candidiasis, the number of granulomas in the brain decreased eightfold after OD treatment compared with antifungal amphotericin B. While the control group of mice died, 60% of OD-treated mice survived (168). …”