Dysfunctional Glymphatic System with Disrupted Aquaporin 4 Expression Pattern on Astrocytes Causes Bacterial Product Accumulation in the CSF during Pneumococcal Meningitis

Authors

Jaqueline S Generoso
Sigrun Thorsdottir
Allan Collodel
Diogo Dominguini
Roberta R E Santo
Fabricia Petronilho
Tatiana Barichello
Federico Iovino

Publication Date

10-26-2022

Journal

mBio

Abstract

Pneumococcal meningitis, inflammation of the meninges due to an infection of the Central Nervous System caused by Streptococcus pneumoniae (the pneumococcus), is the most common form of community-acquired bacterial meningitis globally. Aquaporin 4 (AQP4) water channels on astrocytic end feet regulate the solute transport of the glymphatic system, facilitating the exchange of compounds between the brain parenchyma and the cerebrospinal fluid (CSF), which is important for the clearance of waste away from the brain. Wistar rats, subjected to either pneumococcal meningitis or artificial CSF (sham control), received Evans blue-albumin (EBA) intracisternally. Overall, the meningitis group presented a significant impairment of the glymphatic system by retaining the EBA in the CSF compartments compared to the uninfected sham group. Our results clearly showed that during pneumococcal meningitis, the glymphatic system does not function because of a detachment of the astrocytic end feet from the blood-brain barrier (BBB) vascular endothelium, which leads to misplacement of AQP4 with the consequent loss of the AQP4 water channel's functionality.

Keywords

Animals, Rats, Albumins, Aquaporin 4, Astrocytes, Brain, Glymphatic System, Meningitis, Pneumococcal, Rats, Wistar

Comments

Supplementary Material

PMID: 36036510

DOI

10.1128/mbio.01886-22

PMID

36036510

PMCID

PMC9600563

PubMedCentral® Posted Date

August 2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes