Long-term impact of Sepsis-associated Encephalopathy: Mechanisms and therapeutic options
Acronym: SepMech
Principal Investigator: Dr. Silvio Schmidt
Team: Marcus Böhme
Research Area: E Long-term Sequelae
Project Number: E3.2
Duration: 01.05.2011 - 30.04.2013
Module: Start-up Scientist
The Problem
Survivors of severe sepsis often suffer from cognitive impairments and emotional disturbances like depression and anxiety, which is a serious and debilitating long-term consequence of sepsis. This imposes a growing socioeconomic burden as it affects the independence in daily life, competence in profession, quality of life, and social participation. Brain dysfunctions underlying these long-term impairments are believed to be diffusely distributed but the pathophysiology remains unclear.
Results so far
Based on the general relationship between functional and structural alterations, the combination of repeated structural MRI and Deformation Based Morphometry (DBM) is used to screen the whole brain regarding structural changes and to identify brain regions especially vulnerable to sepsis.
Severe sepsis was induced in rats by peritoneal injection of LPS (lipopolysaccharides) to reach a 50% survival of the septic rats. Severity scores worsened continuously over time reaching maximum between 18 and 24 h, and then survivors recovered to baseline levels in the following 4 days. Three-dimensional MRI was performed before as well as 1, 2, 4, 8 and 12 weeks after sepsis induction. The DBM analysis revealed a pattern of temporal volume changes strongest pronounced as tissue shrinkage in the amygdala. Here, bilateral volume loss by around 12% persisted up to two weeks and then recovered to control values following 12 weeks. In parallel to morphologic changes in the amygdala, the behavioural reactivity to a stressful situation was disturbed in the same time-scale as analyzed using the open-field task.
These preliminary results highlight extensive physical stress and limbic structures as central players mediating cognitive and emotional disturbances following sepsis. We hypothesize that our finding constitutes the morphological equivalent of a post-sepsis stress disorder (PSSD). Our novel hypothesis is now tested by speciἀc behavioural experiments and histological investigations using the LPS and additionally the peritoneal contamination and infection model (PCI).
Contact
Tel.: +49 (0)3641 - 9 32 59 00
Universitätsklinikum Jena
Hans-Berger-Klinik für Neurologie
Experimentelle Neurologie
Forschungszentrum Lobeda
Erlanger Allee 101
07747 Jena