DNase Treatment Prevents Cerebrospinal Fluid Block in Early Experimental Pneumococcal Meningitis.
Journal
Annals of neurology
ISSN: 1531-8249
Titre abrégé: Ann Neurol
Pays: United States
ID NLM: 7707449
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
revised:
29
07
2021
received:
08
03
2021
accepted:
31
07
2021
pubmed:
17
8
2021
medline:
15
12
2021
entrez:
16
8
2021
Statut:
ppublish
Résumé
Streptococcus pneumoniae is the most common cause of bacterial meningitis, a disease that, despite treatment with antibiotics, still is associated with high mortality and morbidity worldwide. Diffuse brain swelling is a leading cause of morbidity in S pneumoniae meningitis. We hypothesized that neutrophil extracellular traps (NETs) disrupt cerebrospinal fluid (CSF) transport by the glymphatic system and contribute to edema formation in S pneumoniae meningitis. We used DNase I treatment to disrupt NETs and then assessed glymphatic function by cisterna magna injections of CSF tracers in a rat model of S pneumoniae meningitis. Our analysis showed that CSF influx into the brain parenchyma, as well as CSF drainage to the cervical lymph nodes, was significantly reduced in the rat model of S pneumoniae meningitis. Degrading NETs by DNase treatment restored glymphatic transport and eliminated the increase in brain weight in the rats. In contrast, first-line antibiotic treatment had no such effect on restoring fluid dynamics. This study suggests that CSF accumulation is responsible for cerebral edema formation and identifies the glymphatic system and NETs as possible new treatment targets in S pneumoniae meningitis. ANN NEUROL 2021;90:653-669.
Substances chimiques
Deoxyribonucleases
EC 3.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
653-669Subventions
Organisme : Crafoordska Stiftelsen
Organisme : Knut och Alice Wallenbergs Stiftelse
Organisme : Lundbeckfonden
Organisme : Novo Nordisk Fonden
Organisme : Vetenskapsrådet
ID : 2018-02340
Informations de copyright
© 2021 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
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