Synaptic transmission dysfunction in experimental septic encephalopathy
Acronym: NeuroSOS-Enc
Principal Investigator: Prof. Dr. Christian Geis
Team: Benedikt Grünewald, Holger Haselmann
Research Area: E Long-term Sequelae
Project Number: E3.3
Duration: 01.07.2012 - 30.06.2015
Module: In-house Professorship Group
The Problem
Encephalopathy is a common neurological complication in patients with sepsis, but the underlying pathophysiological mechanisms are only rudimentarily understood. Here, we aim to elucidate the disturbances of synaptic signalling which cause cognitive and memory deficits with electrophysiological methods and high-resolution imaging techniques.
Results so far
In this project, a multifaceted experimental approach is applied to understand synaptic pathology leading to the symptoms of septic encephalopathy (SE). First, we perform neurophysiological and morphological studies in brain slices obtained from mice after experimental SE. We established the paradigms to analyze changes in synaptic long-term plasticity by recording field potentials or by single cell patch-clamp recording in the hippocampus. Using high-resolution microscopy, we are able to study disturbances in the synaptic architecture of animals with SE. In the next step, we will evaluate the role of tumor necrosis alpha (TNF) in the development of SE. Therefore, we will use genetic and pharmacological methods in the mouse model of SE and test for behavioral, morphological and neurophysiological changes. Furthermore, we will investigate the pathogenic potential of SE patient cerebrospinal fluid (CSF). We will analyze patient CSF samples for the expression pattern of proinflammatory mediators, injury marker and neurotransmitters and test pooled samples in-vivo in an innovative passive-transfer model. Therefore, we established an animal model with implanted intrathecal catheters. Patient CSF can be applied directly to the subarachnoidic space, either by single injection or chronically, and the behavior of the recipient animals can be monitored. Electrophysiological and morphological studies can be performed at the end of the experiment after preparing hippocampal brain slices.
Contact
Tel.: +49 (0)3641 - 9 32 34 01
Universitätsklinikum Jena
Hans-Berger-Klinik für Neurologie
Erlanger Allee 101
07747 Jena