DNase treatment prevents CSF block in early experimental pneumococcal meningitis
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
DNase treatment prevents CSF block in early experimental pneumococcal meningitis. / Pavan, Chiara; Xavier, Anna LR; Ramos, Marta; Fisher, Jane; Kritsilis, Marios; Linder, Adam; Bentzer, Peter; Nedergaard, Maiken; Lundgaard, Iben.
In: Annals of Neurology, Vol. 90, No. 4, 2021, p. 653-669.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - DNase treatment prevents CSF block in early experimental pneumococcal meningitis
AU - Pavan, Chiara
AU - Xavier, Anna LR
AU - Ramos, Marta
AU - Fisher, Jane
AU - Kritsilis, Marios
AU - Linder, Adam
AU - Bentzer, Peter
AU - Nedergaard, Maiken
AU - Lundgaard, Iben
PY - 2021
Y1 - 2021
N2 - Objective S. pneumoniae is the most common cause of bacterial meningitis, a disease that, despite treatment with antibiotics, still is associated with a 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 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, were significantly reduced in the rat model of S. pneumoniae meningitis. Degrading neutrophil extracellular traps (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. This article is protected by copyright. All rights reserved.
AB - Objective S. pneumoniae is the most common cause of bacterial meningitis, a disease that, despite treatment with antibiotics, still is associated with a 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 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, were significantly reduced in the rat model of S. pneumoniae meningitis. Degrading neutrophil extracellular traps (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. This article is protected by copyright. All rights reserved.
KW - Cerebrospinal Fluid
KW - DNase
KW - Glymphatic system
KW - meningitis
KW - NETs
KW - neutrophil extracellular traps
KW - S. pneumoniae
U2 - 10.1002/ana.26186
DO - 10.1002/ana.26186
M3 - Journal article
C2 - 34397111
VL - 90
SP - 653
EP - 669
JO - Annals of Neurology
JF - Annals of Neurology
SN - 0364-5134
IS - 4
ER -
ID: 276648015