The mood-stabilizer lithium prevents hippocampal apoptosis and improves spatial memory in experimental meningitis.

Liechti, Fabian D; Stüdle, Nicolas; Theurillat, Regula; Grandgirard, Denis; Thormann, Wolfgang; Leib, Stephen (2014). The mood-stabilizer lithium prevents hippocampal apoptosis and improves spatial memory in experimental meningitis. PLoS ONE, 9(11), e113607. Public Library of Science 10.1371/journal.pone.0113607

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Pneumococcal meningitis is associated with high morbidity and mortality rates. Brain damage caused by this disease is characterized by apoptosis in the hippocampal dentate gyrus, a morphological correlate of learning deficits in experimental paradigms. The mood stabilizer lithium has previously been found to attenuate brain damage in ischemic and inflammatory diseases of the brain. An infant rat model of pneumococcal meningitis was used to investigate the neuroprotective and neuroregenerative potential of lithium. To assess an effect on the acute disease, LiCl was administered starting five days prior to intracisternal infection with live Streptococcus pneumoniae. Clinical parameters were recorded, cerebrospinal fluid (CSF) was sampled, and the animals were sacrificed 42 hours after infection to harvest the brain and serum. Cryosections of the brains were stained for Nissl substance to quantify brain injury. Hippocampal gene expression of Bcl-2, Bax, p53, and BDNF was analyzed. Lithium concentrations were measured in serum and CSF. The effect of chronic lithium treatment on spatial memory function and cell survival in the dentate gyrus was evaluated in a Morris water maze and by quantification of BrdU incorporation after LiCl treatment during 3 weeks following infection. In the hippocampus, LiCl significantly reduced apoptosis and gene expression of Bax and p53 while it increased expression of Bcl-2. IL-10, MCP-1, and TNF were significantly increased in animals treated with LiCl compared to NaCl. Chronic LiCl treatment improved spatial memory in infected animals. The mood stabilizer lithium may thus be a therapeutic alternative to attenuate neurofunctional deficits as a result of pneumococcal meningitis.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases > Research
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases > Laboratory for Clinical Pharmacology

UniBE Contributor:

Theurillat, Regula; Grandgirard, Denis; Thormann, Wolfgang and Leib, Stephen

Subjects:

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

ISSN:

1932-6203

Publisher:

Public Library of Science

Funders:

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

Language:

English

Submitter:

Stephen Leib

Date Deposited:

06 Feb 2015 16:34

Last Modified:

16 Mar 2021 14:34

Publisher DOI:

10.1371/journal.pone.0113607

PubMed ID:

25409333

BORIS DOI:

10.7892/boris.61932

URI:

https://boris.unibe.ch/id/eprint/61932

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