The antidepressant fluoxetine protects the hippocampus from brain damage in experimental pneumococcal meningitis.

Liechti, F D; Grandgirard, Denis; Leib, Stephen (2015). The antidepressant fluoxetine protects the hippocampus from brain damage in experimental pneumococcal meningitis. Neuroscience, 297, pp. 89-94. Elsevier 10.1016/j.neuroscience.2015.03.056

[img] Text
__nas-ifik.unibe.ch_ifik_Forschung_Gr_Leib_SHARED GROUP FOLDER_Manuscripts_ACCEPTED_Fluoxetine in PM_Submission Neuroscience_The antidepressant fluoxetine protects the hippocampus from brain damage in experimental pneumococcal meningitis.pdf - Published Version
Restricted to registered users only
Available under License Publisher holds Copyright.

Download (262kB) | Request a copy

BACKGROUND High mortality and morbidity rates are observed in patients with bacterial meningitis (BM) and urge for new adjuvant treatments in addition to standard antibiotic therapies. In BM the hippocampal dentate gyrus is injured by apoptosis while in cortical areas ischemic necrosis occurs. Experimental therapies aimed at reducing the inflammatory response and brain damage have successfully been evaluated in animal models of BM. Fluoxetine (FLX) is an anti-depressant of the selective serotonin reuptake inhibitors (SSRI) and was previously shown to be neuroprotective in vitro and in vivo. We therefore assessed the neuroprotective effect of FLX in experimental pneumococcal meningitis. METHODS Infant rats were infected intracisternally with live Streptococcus pneumoniae. Intraperitoneal treatment with FLX (10mgkg(-1)d(-1)) or an equal volume of NaCl was initiated 15min later. 18, 27, and 42h after infection, the animals were clinically (weight, clinical score, mortality) evaluated and subject to a cisternal puncture and inflammatory parameters (i.e., cyto-/chemokines, myeloperoxidase activity, matrix metalloproteinase concentrations) were measured in cerebrospinal fluid (CSF) samples. At 42h after infection, animals were sacrificed and the brains collected for histomorphometrical analysis of brain damage. RESULTS A significant lower number of animals treated with FLX showed relevant hippocampal apoptosis when compared to littermates (9/19 animals vs 18/23, P=0.038). A trend for less damage in cortical areas was observed in FLX-treated animals compared to controls (13/19 vs 13/23, P=ns). Clinical and inflammatory parameters were not affected by FLX treatment. CONCLUSION A significant neuroprotective effect of FLX on the hippocampus was observed in acute pneumococcal meningitis in infant rats.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases
04 Faculty of Medicine > Faculty Institutions > Teaching Staff, Faculty of Medicine
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases > Research

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Grandgirard, Denis and Leib, Stephen

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

0306-4522

Publisher:

Elsevier

Funders:

[4] Swiss National Science Foundation
[24] Gottfried und Julia Bangerter- Rhyner Stiftung

Language:

English

Submitter:

Stephen Leib

Date Deposited:

05 May 2015 14:56

Last Modified:

27 Apr 2016 08:02

Publisher DOI:

10.1016/j.neuroscience.2015.03.056

PubMed ID:

25839149

Uncontrolled Keywords:

Streptococcus pneumoniae, hippocampus, neuroinfection, neuroinflammation, stem cell niche

BORIS DOI:

10.7892/boris.68009

URI:

https://boris.unibe.ch/id/eprint/68009

Actions (login required)

Edit item Edit item
Provide Feedback