minocycline and Toxoplasmosis--Cerebral

A plethora of evidence shows that activated microglia play a critical role in the pathogenesis of the central nervous system (CNS). Toxoplasmic encephalitis (TE) frequently occurs in HIV/AIDS patients. However, knowledge remains limited on the contributions of activated microglia to the pathogenesis of TE.. A murine model of reactivated encephalitis was generated in a latent infection with Toxoplasma gondii induced by cyclophosphamide. The neuronal apoptosis in the CNS and the profile of pro-inflammatory cytokines were assayed in both in vitro and in vivo experiments.. Microglial cells were found to be activated in the cortex and hippocampus in the brain tissues of mice. The in vivo expression of interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS) were up-regulated in TE mice, and accordingly, the neuronal apoptosis was significantly increased. The results were positively correlated with those of the in vitro experiments. Additionally,apoptosis of the mouse neuroblastoma type Neuro2a (N2a) remarkably increased when the N2a was co-cultured in transwell with microglial cells and Toxoplasma tachyzoites. Both in vivo and in vitro experiments showed that minocycline (a microglia inhibitor) treatment notably reduced microglial activation and neuronal apoptosis.. Activated microglia contribute to neuronal apoptosis in TE and inhibition of microglia activation might represent a novel therapeutic strategy of TE.

Topics: Animals; Anti-Bacterial Agents; Apoptosis; Cell Line; Cerebral Cortex; Cytokines; Gene Expression Regulation; Hippocampus; Mice; Mice, Inbred BALB C; Microglia; Minocycline; Neurons; Toxoplasmosis, Cerebral

HIV-infected patients with opportunistic infections receive therapeutic regimens that often contain numerous drugs and are then exposed to potential drug-to-drug interactions. We report here an unusual case of relapse of toxoplasmic encephalitis in an HIV-infected patient, possibly due to a drug-to-drug interaction between dapsone and minocycline.

Topics: Adult; Dapsone; Drug Interactions; Encephalitis; HIV Infections; HIV-1; Humans; Male; Minocycline; Recurrence; Toxoplasma; Toxoplasmosis, Cerebral

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Clarithromycin; Drug Therapy, Combination; Humans; Male; Minocycline; Toxoplasmosis, Cerebral