Long-term cognitive impairment, neuronal loss and reduced cortical cholinergic innervation after recovery from sepsis in a rodent model.
Sepsis is a disease with a high and growing prevalence worldwide. Most studies on sepsis up to date have been focused on reduction of short-term mortality. This study investigates cognitive and neuroanatomical long-term consequences of sepsis in a rat model. Sepsis was induced in male Wistar rats weighing 250-300 g by an i.p. injection of bacterial lipopolysaccharide (LPS, 10 mg/kg). Three months after complete recovery from sepsis, animals showed memory deficits in the radial maze and changes in open field exploratory patterns but unaffected inhibitory avoidance learning. Behavioral findings were matched by sepsis-induced loss of neurons in the hippocampus and the prefrontal cortex on serial sections after NeuN-staining and reduced cholinergic innervation in the parietal cortex measured by immunoradiography of vesicular acetylcholine transporter (VAChT). Together these results suggest that sepsis can induce persistent behavioral and neuroanatomical changes and warrant studies of the neurological long-term consequences of sepsis in humans.
Semmler
Alexander
A
Department of Neurology, Sigmund-Freud-Strasse 25, University Hospital Bonn, 53105 Bonn, Germany. alexander.semmler@ukb.uni-bonn.de
Frisch
Christian
C
Debeir
Thomas
T
Ramanathan
Mutiah
M
Okulla
Thorsten
T
Klockgether
Thomas
T
Heneka
Michael T
MT
D000818:Animals; D002540:Cerebral Cortex / Q000473:pathology*; D003072:Cognition Disorders / Q000209:etiology*; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011134:Polysaccharides; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000502:physiology*; D018805:Sepsis / Q000139:chemically induced / Q000150:complications / Q000473:pathology*; D013997:Time Factors; D033921:Vesicular Transport Proteins / Q000378:metabolism*
D011134:Polysaccharides; D033921:Vesicular Transport Proteins; D010751:Phosphopyruvate Hydratase