Candida albicans causes brain regional invasion and necrosis, and activation of microglia during lethal neonatal neurocandidiasis

Neurocandidiasis is a fungal infection that primarily affects neonates, which is associated with 70% case fatality rates, while pediatric patients who survive infection often have long-term neurological sequelae, making it a clinical requirement to understand the pathogenesis of neonatal neurocandidiasis. Currently, the brain regions to Candida albicans invasion during the neonatal period are not characterized. In this study, 0-day-old mice were infected with C. albicans intravenously to determine dissemination and invasion into the brain at different times post-infection by fungal burden assay and histopathological analysis, additionally cellular death and microglial activation were evaluated by flow cytometry. The results evidenced the dissemination of C. albicans within the first hour of infection in the brain. The meninges were the initial site of invasion during the first 6 hours post infection and then filamentous structures into the brain parenchyma increases during infection, the anatomic regions most susceptible to invasion being the cerebral cortex, thalamus, hypothalamus, midbrain, pons, and medulla oblongata. Furthermore, C. albicans invasion of brain tissue results in cell necrosis and activation of microglia as a consequence of fungal invasion.