Anti-inflammatory and Oto-Protective Effect of the Small Heat Shock Protein Alpha B-Crystallin (HspB5) in Experimental Pneumococcal Meningitis.

Erni, Silvia T.; Fernandes, Gabriella; Buri, Michelle; Perny, Michael; Rutten, Rolf Jan; van Noort, Johannes M; Senn, Pascal; Grandgirard, Denis; Roccio, Marta; Leib, Stephen (2019). Anti-inflammatory and Oto-Protective Effect of the Small Heat Shock Protein Alpha B-Crystallin (HspB5) in Experimental Pneumococcal Meningitis. Frontiers in neurology, 10(570), p. 570. Frontiers Media S.A. 10.3389/fneur.2019.00570

[img]
Preview
Text
fneur-10-00570.pdf - Published Version
Available under License Creative Commons: Attribution (CC-BY).

Download (3MB) | Preview

Sensorineural hearing loss is the most common long-term deficit after pneumococcal meningitis (PM), occurring in up to 30% of surviving patients. The infection and the following overshooting inflammatory host response damage the vulnerable sensory cells of the inner ear, resulting in loss of hair cells and spiral ganglion neurons, ultimately leading to elevated hearing thresholds. Here, we tested the oto-protective properties of the small heat shock protein alpha B-crystallin (HspB5) with previously reported anti-inflammatory, anti-apoptotic and neuroprotective functions, in an experimental model of PM-induced hearing loss. We analyzed the effect of local and systemic delivery of HspB5 in an infant rat model of PM, as well as ex vivo, using whole mount cultures. Cytokine secretion profile, hearing thresholds and inner ear damage were assessed at predefined stages of the disease up to 1 month after infection. PM was accompanied by elevated pro-inflammatory cytokine concentrations in the cerebrospinal fluid (CSF), leukocyte and neutrophil infiltration in the perilymphatic spaces of the cochlea with neutrophils extracellular trap formation during the acute phase of the disease. Elevated hearing thresholds were measured after recovery from meningitis. Intracisternal but not intraperitoneal administration of HspB5 significantly reduced the levels of TNF-α, IL-6 IFN-γ and IL-10 in the acute phase of the disease. This resulted in a greater outer hair cell survival, as well as improved hearing thresholds at later stages. These results suggest that high local concentrations of HspB5 are needed to prevent inner ear damage in acute PM. HspB5 represents a promising therapeutic option to improve the auditory outcome and counteract hearing loss after PM.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases
04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Ear, Nose and Throat Disorders (ENT)
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases > Research

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Erni, Silvia; Fernandes Pires, Gabriella Patrizia; Buri, Michelle; Perny, Michael; Grandgirard, Denis; Roccio, Marta and Leib, Stephen

Subjects:

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

ISSN:

1664-2295

Publisher:

Frontiers Media S.A.

Funders:

[4] Swiss National Science Foundation
[18] European Research Council

Projects:

[UNSPECIFIED] This work was supported by a Eurostars project (HEARit, Project ID: E!10491) through Innosuisse (Swiss Innovation Agency), and by the Swiss National Science Foundation (grant 162583).

Language:

English

Submitter:

Stephen Leib

Date Deposited:

18 Sep 2019 16:22

Last Modified:

02 Nov 2019 18:29

Publisher DOI:

10.3389/fneur.2019.00570

PubMed ID:

31244750

Uncontrolled Keywords:

HspB5 S.pneumoniae hair cells inflammation neutrophil infiltration oto-protection sensorineural hearing loss

BORIS DOI:

10.7892/boris.133326

URI:

https://boris.unibe.ch/id/eprint/133326

Actions (login required)

Edit item Edit item
Provide Feedback