Il1-β involvement in cognitive impairment after sepsis.
Sepsis is defined as the host's reaction to infection and characterised by a systemic inflammatory response with important clinical implications. Central nervous system dysfunction secondary to sepsis is associated with local generation of pro- and anti-inflammatory cytokines, impaired cerebral microcirculation, an imbalance of neurotransmitters, apoptosis and cognitive impairment. It's known that the IL-1β is one of the first cytokines to be altered. Thus, the objective of this study was to evaluate the role of IL-1β in cognitive parameters in brain tissue through the use of an IL-1β (IL-1ra) receptor antagonist up to 10 days and to assess blood-brain barrier permeability, cytokine levels, oxidative parameters and energetic metabolism up to 24 h, after sepsis induction. To this aim, we used sham-operated Wistar rats or submitted to the cecal ligation and perforation (CLP) procedure. Immediately after, the animals received one dose of 10 μg of IL-1ra. After 24 h, the rats were killed and were evaluated for biochemical parameters in the pre-frontal cortex, hippocampus and striatum. After 10 days, the animals were submitted to the habituation to the open field and step-down inhibitory avoidance task. We observed that the use of IL-1ra reverted the increase of blood-brain barrier permeability in the pre-frontal cortex, hippocampus and striatum; the increase of IL-1β, IL1-6 and TNF-α levels in the pre-frontal cortex and striatum; the decrease of complex I activity in the pre-frontal, hippocampus and striatum; the increase of oxidative parameters in pre-frontal cortex, hippocampus and striatum; and cognitive impairment. In conclusion, the results observed in this study reinforce the role of acute brain inflammatory response, in particular, the IL1β response, in the cognitive impairment associated with sepsis.
Laboratory of Neurosciences and National Institute for Translational Medicine (INCT-TM), Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, 88806-000, Criciúma, SC, Brazil.
Francielle
F
Mina
Clarissa M
CM
Comim
Diogo
D
Dominguini
Omar J
OJ
Cassol
Dhébora M
DM
Dall Igna
Gabriela K
GK
Ferreira
Milena C
MC
Silva
Leticia S
LS
Galant
Emílio L
EL
Streck
João
J
Quevedo
Felipe
F
Dal-Pizzol
D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D003072:Cognition Disorders / Q000378:metabolism* / Q000473:pathology; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D008297:Male; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000378:metabolism* / Q000523:psychology
D053583:Interleukin-1beta