Abstract
The administration of microbial neuraminidase into the brain ventricular cavities of rodents represents a model of acute aseptic neuroinflammation. Ependymal cell death and hydrocephalus are unique features of this model. Here we demonstrate that activated microglia participates in ependymal cell death. Co-cultures of pure microglia with ependymal cells (both obtained from rats) were performed, and neuraminidase or lipopolysaccharide were used to activate microglia. Ependymal cell viability was unaltered in the absence of microglia or inflammatory stimulus (neuraminidase or lipopolysaccharide). The constitutive expression by ependymal cells of receptors for cytokines released by activated microglia, such as IL-1β, was demonstrated by qPCR. Besides, neuraminidase induced the overexpression of both receptors in ventricular wall explants. Finally, ependymal viability was evaluated in the presence of functional blocking antibodies against IL-1β and TNFα. In the co-culture setting, an IL-1β blocking antibody prevented ependymal cell death, while TNFα antibody did not. These results suggest that activated microglia are involved in the ependymal damage that occurs after the administration of neuraminidase in the ventricular cavities, and points to IL-1β as possible mediator of such effect. The relevance of these results lies in the fact that brain infections caused by neuraminidase-bearing pathogens are frequently associated to ependymal death and hydrocephalus.
Highlights
Ependymal cells form a cuboidal monostratified epithelium that covers the wall of the cerebral ventricles and the central canal of the spinal cord
Ependymal damage in ventricular wall explants co‐cultured with NA activated microglia Activated microglia overexpress the pro-inflammatory cytokines Interleukin 1 beta (IL-1β) and Tumor necrosis factor-alpha (TNFα) [6, 34, 43]
In a previous work by our group using pure microglial cultures obtained from mice, the addition of NA to the culture media provoked an increase in the expression, measured by Quantitative polymerase chain reaction (qPCR), of the cytokines IL-1β, TNFα and IL-6 [40]
Summary
Ependymal cells form a cuboidal monostratified epithelium that covers the wall of the cerebral ventricles and the central canal of the spinal cord. One of their distinctive morphological characteristics is that they are multiciliated, which allows them to perform an asymmetric shake that generates a constant flow of cerebrospinal fluid (CSF) [1, 2]. Neuraminidase (NA) is a sialidase found in the membranes or cell walls of certain viruses and bacteria Some of these microorganisms displaying NA in their coats induce damage in ependymal cells when invading the Fernández‐Arjona et al Fluids Barriers CNS (2021) 18:15 central nervous system (CNS), as occurs with Streptococcus pneumoniae. NA-bearing viruses from orthomyxoviridae family (influenza viruses), and paramyxoviridae family (causing mumps and measles) have been associated to ependymal death and hydrocephalus [19,20,21,22,23,24,25,26,27,28]
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