EFFECTS OF PENTOXIFYLLINE OR DEXAMETHASONE IN COMBINATION WITH AMPHOTERICIN-B IN EXPERIMENTAL MURINE CEREBRAL CRYPTOCOCCOSIS - EVIDENCE OF NEUROEXCITATORY PATHOGENIC MECHANISMS

In a murine model of intracerebral infection by Cryptococcus neoforman s the therapeutic effects of pentoxifylline or dexamethasone were stud ied alone and in combination with amphotericin B. Assessed parameters were mean survival time, brain histopathology index, amounts of glutam ate and gamma-aminobutyric acid in the brain, and yeast CFU per brain. Survival increased significantly in mice treated with dexamethasone, amphotericin B, amphotericin B plus dexamethasone, and amphotericin B plus pentoxifylline; the latter had significantly longer survival than other treated groups. Indices of histopathological damage were simila r in all treated groups. In infected untreated mice, the amounts of gl utamate in the brain were decreased, presumably by depletion. In mice treated with amphotericin B plus dexamethasone, glutamate levels retur ned to the range of control mice. No differences in the amounts of gam ma-aminobutyric acid were found between control and treatment groups. Brain fungal counts were significantly lower in mice treated with amph otericin B, amphotericin B plus dexamethasone, and amphotericin B plus pentoxifylline than in untreated animals. In this model, pentoxifylli ne in combination with amphotericin B improved survival, decreasing th e fungal burden, and has potential as adjuvant therapy in cerebral cry ptococcosis.