The inflammatory response and neuronal injury in Streptococcus suis meningitis

Jana Seele,Andreas Beineke,Peter Valentin-Weigand,Asparouh I Iliev,Nicole De Buhr,Stephanie Bunkowski,Wolfgang Brück,Roland Nau,Christoph G Baums,Simone C Tauber

doi:10.1186/s12879-018-3206-6

Abstract

BackgroundMany of the currently used models of bacterial meningitis have limitations due to direct inoculation of pathogens into the cerebrospinal fluid or brain and a relatively insensitive assessment of long-term sequelae. The present study evaluates the utility of a Streptococcus (S.) suis intranasal infection model for the investigation of experimental therapies in meningitis.MethodsWe examined the brains of 10 piglets with S. suis meningitis as well as 14 control piglets by histology, immunohistochemistry and in-situ tailing for morphological alterations in the hippocampal dentate gyrus and microglial activation in the neocortex.ResultsIn piglets with meningitis, the density of apoptotic neurons was significantly higher than in control piglets. Moreover, scoring of microglial morphology revealed a significant activation of these cells during meningitis. The slight increase in the density of dividing cells, young neurons and microglia observed in piglets suffering from meningitis was not statistically significant, probably because of the short time frame between onset of clinical signs and organ sampling.ConclusionsThe morphological changes found during S. suis meningitis are in accordance with abnormalities in other animal models and human autopsy cases. Therefore, the pig should be considered as a model for evaluating effects of experimental therapeutic approaches on neurological function in bacterial meningitis.

Highlights

Many of the currently used models of bacterial meningitis have limitations due to direct inoculation of pathogens into the cerebrospinal fluid or brain and a relatively insensitive assessment of long-term sequelae
In this study the brains of piglets which had been infected intranasally with S. suis serotype 2 strain 10 were analysed for leukocyte infiltration, microglial and astrocyte density, ischemia, axonal injury, neuronal apoptosis and neural proliferation in the dentate gyrus of the hippocampal formation as well as microglial activation in the neocortical layers I-III
In the present study we aimed at assessing whether the morphological alterations seen in the brains of piglets with S. suis meningitis are comparable to the abnormalities observed in human autopsy cases and in rodent models of bacterial meningitis

Summary

Introduction

Many of the currently used models of bacterial meningitis have limitations due to direct inoculation of pathogens into the cerebrospinal fluid or brain and a relatively insensitive assessment of long-term sequelae. The present study evaluates the utility of a Streptococcus (S.) suis intranasal infection model for the investigation of experimental therapies in meningitis. Streptococcus (S.) suis is an important pathogen in veterinary medicine. Prevention and treatment of S. suis infections contribute substantially to the high rate of antibiotic consumption in the pig producing industry [1]. More than 50% of the cases in pigs occur below the age of 12 weeks [2]. Transmission to humans usually occurs by close contact with sick or asymptomatic carrier pigs or contaminated food. S. suis is the most frequent cause of human bacterial meningitis in

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