[en] To date, long-term consequences of septic encephalopathy on cerebral metabolism, cognition, learning, and memory capabilities and factors involved are poorly understood. In this study, we used a murine sepsis model to demonstrate that bacterial lipopolysaccharide (LPS) causes long-term cognitive deficits in mice. Two months after LPS treatment, wild-type mice committed more working and reference memory errors than controls. The behavioral impairment was independent of the cerebral glucose uptake as evidenced by (18)F-Fluordeoxyglucose small animal positron emission tomography. In contrast, mice deficient for the inducible nitric oxide synthase gene (NOS2-/-) did not show any cognitive changes when challenged with LPS. Immunohistochemical analysis demonstrated that LPS did not lead to neuronal cell death but caused sustained microglial activation in wild-type as compared to NOS2-/- mice. Expression analysis showed that LPS-treated NOS2-/- mice had lower brain mRNA levels for proinflammatory factors compared with wild-type mice. Expression analysis demonstrated distinct changes in the content of synaptic proteins in wild-type mice, which were not observed in the NOS2-/- mice. Together, this data set outlines the importance of the NOS2 activation for long-term cerebral changes after severe sepsis.
Disciplines :
Neurology
Author, co-author :
Weberpals, Marc; Department of Neurology, University of Bonn, 53127 Bonn, Germany
Hermes, Michael; Department of Neurology, University of Bonn, 53127 Bonn, Germany
Hermann, S; Department of Nuclear Medicine, University of Münster, 48149 Münster, Germany
Kummer, Markus P; Department of Neurology, University of Bonn, 53127 Bonn, Germany
Terwel, Dick; Department of Neurology, University of Bonn, 53127 Bonn, Germany
Semmler, Alexander; Department of Neurology, University of Bonn, 53127 Bonn, Germany
Berger, Meike; Department of Physiology I, University of Münster, 48149 Münster, Germany
Schäfers, Michael; European Institute of Molecular Imaging, University of Münster, 48149 Münster, Germany
HENEKA, Michael ; Department of Neurology, University of Bonn, 53127 Bonn, Germany
External co-authors :
yes
Language :
English
Title :
NOS2 gene deficiency protects from sepsis-induced long-term cognitive deficits.
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