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DNase Treatment Prevents Cerebrospinal Fluid Block in Early Experimental Pneumococcal Meningitis
Author(s) -
Pavan Chiara,
L. R. Xavier Anna,
Ramos Marta,
Fisher Jane,
Kritsilis Marios,
Linder Adam,
Bentzer Peter,
Nedergaard Maiken,
Lundgaard Iben
Publication year - 2021
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.26186
Subject(s) - streptococcus pneumoniae , cerebrospinal fluid , meningitis , medicine , glymphatic system , parenchyma , cisterna magna , antibiotics , immunology , microbiology and biotechnology , pathology , biology , surgery
Objective 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. Methods 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. Results 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. Interpretation 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