Vergleich des Verlaufes bakterieller Infektionen des zentralen Nervensystems bei alten und jungen Mäusen am Beispiel der Escherichia coli- und Streptococcus pneumoniae-Meningitis

Comparison of the course of bacterial infections of the central nervous systems between old and young mice using the example of Escherichia coli- and Streptococcus pneumoniae-meningitis

by Anja Manig
Doctoral thesis
Date of Examination:2015-04-01
Date of issue:2015-03-25
Advisor:PD Dr. Sandra Schütze
Referee:PD Dr. Sandra Schütze
Referee:PD Dr. Michael Weig
Persistent Address: http://dx.doi.org/10.53846/goediss-4994

 

 

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Abstract

English

Bacterial meningitis, as well as other bacterial infections, shows a more severe disease course, a higher rate of complications and higher mortality in elderly patients when compared with younger patients. As such, in the context of the aging population, a better understanding of this clinical phenomenon is needed. With both old and young C57BL/6-mice the course of bacterial meningitis for the agents E. coli und S. pneumoniae was investigated. The mice were infected intracerebrally with the agent and the course of the disease was monitored via control of weight, evaluation of the state of health and the assessment of motor skills by means of the tightrope test. The bacterial concentration in the blood, the cerebellum and the spleen were measured following death or sacrifice at 15 days. In addition the cytokine concentrations in the serum and cerebellum were measured via ELISA and the degree of meningeal inflammation via staining of neutrophilic granulocytes in histological slices was evaluated. In accordance with clinical findings, for the course of the E. coli-meningitis there was a higher mortality rate for the old mice with 73 % in comparison to the young mice with 46 %. There also was earlier clinical deterioration and higher weight loss of the old mice. Old mice were less able to eliminate the agent E. coli after the infection compared to young mice, which may be the result of reduced phagocytic ability of microglia and macrophages in old age. In addition, 24 hours after intracerebral infection with a lethal dose of E. coli the old mice showed a lower cytokine concentration of IL-6 and KC within the serum, which is a sign of reduced systemic inflammatory response. Regarding the S. pneumoniae-meningitis no differences between old and young mice concerning mortality, course of disease and bacterial concentration were detected. The reduced resistance and impaired coping mechanisms for infections of the central nervous system appears to therefore be agent specific. In this study, the clinical phenomenon of higher mortality and more severe disease progression of bacterial meningitis in the elderly was demonstrated with a mouse model of E. coli-meningitis. On the basis of this model new strategies for prevention and therapy of bacterial meningitis in elderly patients could potentially be developed and tested.
Keywords: meningitis; streptococcus pneumoniae; mice; age; elderly; escherichia coli
Schlagwörter: Meningitis; Streptococcus pneumoniae; Escherichia coli; Maus; Alter
 
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