Ultrastructural analysis of growth of Nocardia asteroides during invasion of the murine brain

Abstract

BALB/c mice were infected with 106 CFU of log-phase cells of Nocardia asteroides GUH-2 by tail vein injection (at this lethal inoculum dose, approximately 800 to 1,000 CFU becomes deposited in the brain). At 24 h after infection, the ultrastructural interactions of the nocardiae during growth within the murine brain were investigated. The nocardiae grew perivascularly in the pons, substantia nigra, hypothalamus, and thalamus portions of the brain, where they were either within or associated with most brain cell types. There appeared to be a propensity for growth within the soma of neurons and their axonal extensions. The nocardial cells were surrounded by 1 to 30 layers of membrane, and the innermost membrane was usually tightly adherent to the cell wall. This compartmentalization of nocardiae within brain cells could contribute to their failure to induce an inflammatory response or a cytopathic effect. Nevertheless, the bacteria were able to obtain adequate nutrients from the host to grow within the brain. The nocardiae were not completely inert, since some of the brain cells showed signs of degeneration. The myelin sheaths of axons were the most strongly affected, and there was evidence of demyelinization and axonal degeneration. Nocardiae growing within brain cells were

Activation of murine microglial cell lines by lipopolysaccharide and interferon‐γ causes NO‐mediated decreases in mitochondrial and cellular function

“…In addition, there is increasing evidence to support the hypothesis that these neurological disorders result from an inability of these cell populations to protect themselves from oxidative and nitrosative stress imposed upon them by cells such as activated microglia. In this context, microglia have been found in increased numbers in the brain lesions associated with a variety of CNS pathologies including Parkinson's and Alzheimer's diseases (McGeer et al ., 1988; Cras et al ., 1990), Huntington's disease (McGeer et al ., 1987) and multiple sclerosis (Li et al ., 1996), as well as infections within the CNS caused by bacteria (Beaman, 1993), viruses (Dhib‐Jalbut et al ., 1996) and fungi (Blasi et al ., 1992).…”

Nocardiosis cerebral parvosintomática, en pacientes inmunocomprometidos

“…Se sabe que la Nocardia puede penetrar al SNC, sin generar una respuesta inflamatoria ni modificar la barrera hematoencefálica 1,23 , lo que permite mantener el "santuario" inmunológico, protegiendo así el lento desarrollo de la bacteria. Además experimentalmente se ha visto que la Nocardia es capaz de crecer intracelularmente, tanto en neuronas como en células de la glía, condición que también la protegería 24 . Es posible que el desarrollo de estos abscesos o granulomas dentro del SNC protegidos por la barrera sean tan lento que permitan la compensación del sistema, siempre que se mantenga indemne la barrera hematoencefálica, cuya ruptura puede ser el desencadenante de síntomas inespecíficos como cefalea, fiebre o convulsiones aún en ausencia de síntomas focales.…”

Acid‐Fastness of Nocardia asteroides GUH‐2 Cultured in Brain Heart Infusion Broth Supplemented with Paraffin

“…The production of acid-fast properties within many cells of the strain GUH-2 may be enhanced by paraffin and stained red by the acid-fast stain. The utilization of lipids by filamentous nocardiae may, in part, explain the nocardial invasion of the murine brain and the disruption of lipid-rich myelin sheaths in the central nervous system (CNS) (3,17). In addition to the Gram stain, the acid-fast stain appears to be useful for investigating the localization of acid-fast nocardiae in the brain.…”