Gut Microbiota Reconstruction Following Host Infection with Blood-stage Plasmodium berghei ANKA Strain in a Murine Model.

Malaria remains a global health problem. The relationship between Plasmodium spp. and the gut microbiota as well as the impact of Plasmodium spp. on the gut microbiota in vertebrate hosts is unclear. The aim of the current study was to evaluate the effect of blood-stage Plasmodium parasites on the gut microbiota of mice. The gut microbiota was analyzed by 16S rRNA sequencing and bioinformatic analyses at three stages. The gut microbiota changed during the three phases: the healthy stage, the infection stage, and the cure stage (on the 9th day after malarial elimination). Moreover, the gut microbiota of these infected animals did not recover after malaria infection. There were 254 operational taxonomic units (OTUs) across all three stages, and there were unique strains or OTUs at each stage of the experiment. The percentages of community abundance of 8 OTUs changed significantly (P<0.05). The dominant OTU in both the healthy mice and the mice with malaria was OTU265, while that in the cured mice was OTU234. In addition, the changes in OTU147 were the most noteworthy. Its percentage of community abundance varied greatly, with higher values during malaria than before malaria infection and after malaria elimination. These results indicated that the external environment influenced the gut microbiota after host C57BL/6 mice were infected with blood-stage P. berghei ANKA and that the same was true during and after elimination of blood-stage P. berghei ANKA. In addition, we could not isolate OTU147 for further study. This study identified gut microbiota components that were reconstructed after infection by and elimination of blood-stage P. berghei ANKA in host C57BL/6 mice, and this process was affected by P. berghei ANKA and the external environment of the host.

Ablation of cyclooxygenase-2 in forebrain neurons is neuroprotective and dampens brain inflammation after status epilepticus.

Cyclooxygenase-2 (COX-2), a source of inflammatory mediators and a multifunctional neuronal modulator, is rapidly induced in select populations of cortical neurons after status epilepticus. The consequences of rapid activity-triggered induction of COX-2 in neurons have been the subject of much study and speculation. To address this issue directly, we created a mouse in which COX-2 is conditionally ablated in selected forebrain neurons. Results following pilocarpine-induced status epilepticus indicate that neuronal COX-2 promotes early neuroprotection and then delayed neurodegeneration of CA1 pyramidal neurons, promotes neurodegeneration of nearby somatostatin interneurons in the CA1 stratum oriens and dentate hilus (which themselves do not express COX-2), intensifies a broad inflammatory reaction involving numerous cytokines and other inflammatory mediators in the hippocampus, and is essential for development of a leaky blood-brain barrier after seizures. These findings point to a profound role of seizure-induced neuronal COX-2 expression in neuropathologies that accompany epileptogenesis.