Anaesthesia makes up the largest hospital speciality and has a huge role to play in nearly every aspect of any hospital from operating theatres to accident and emergency, to the labour ward, and to intensive care. Our research ranges from basic molecular research into mechanisms of anaesthesia to investigating the clinical impact of novel anaesthetic agents.
Our research covers the entirety of patient’s perioperative journey and through this, we aim to deliver the greatest impact. The section has been pioneering in the development of novel technologies to facilitate the delivery of anaesthetic agents and has also made pivotal in-roads into the mechanism of action of anaesthetic agents and their wider application to other diseases (such as their protective roles in brain injury and in cancer).
@article{Terrando:2010:10.1186/cc9019,
author = {Terrando, N and Fidalgo, AR and Vizcaychipi, MP and Cibelli, M and Ma, D and Monaco, C and Feldmann, M and Maze, M},
doi = {10.1186/cc9019},
journal = {Critical Care (UK)},
pages = {1--9},
title = {The impact of IL-1 modulation on the development of lipopolysaccharide-induced cognitive dysfunction},
url = {http://dx.doi.org/10.1186/cc9019},
volume = {14},
year = {2010}
}
TY - JOUR
AB - IntroductionThe impact of pro-inflammatory cytokines on neuroinflammation and cognitive function after lipopolysaccharide (LPS) challenge remains elusive. Herein we provide evidence that there is a temporal correlation between high-mobility group box 1 (HMGB-1), microglial activation, and cognitive dysfunction. Disabling the interleukin (IL)-1 signaling pathway is sufficient to reduce inflammation and ameliorate the disability.MethodsEndotoxemia was induced in wild-type and IL-1R-/- mice by intra peritoneal injection of E. Coli LPS (1 mg/kg). Markers of inflammation were assessed both peripherally and centrally, and correlated to behavioral outcome using trace fear conditioning.ResultsIncrease in plasma tumor necrosis factor-α (TNFα) peaked at 30 minutes after LPS challenge. Up-regulation of IL-1β, IL-6 and HMGB-1 was more persistent, with detectable levels up to day three. A 15-fold increase in IL-6 and a 6.5-fold increase in IL-1β mRNA at 6 hours post intervention (P < 0.001 respectively) was found in the hippocampus. Reactive microgliosis was observed both at days one and three, and was associated with elevated HMGB-1 and impaired memory retention (P < 0.005). Preemptive administration of IL-1 receptor antagonist (IL-1Ra) significantly reduced plasma cytokines and hippocampal microgliosis and ameliorated cognitive dysfunction without affecting HMGB-1 levels. Similar results were observed in LPS-challenged mice lacking the IL-1 receptor to those seen in LPS-challenged wild type mice treated with IL-1Ra.ConclusionsThese data suggest that by blocking IL-1 signaling, the inflammatory cascade to LPS is attenuated, thereby reducing microglial activation and preventing the behavioral abnormality.
AU - Terrando,N
AU - Fidalgo,AR
AU - Vizcaychipi,MP
AU - Cibelli,M
AU - Ma,D
AU - Monaco,C
AU - Feldmann,M
AU - Maze,M
DO - 10.1186/cc9019
EP - 9
PY - 2010///
SN - 1364-8535
SP - 1
TI - The impact of IL-1 modulation on the development of lipopolysaccharide-induced cognitive dysfunction
T2 - Critical Care (UK)
UR - http://dx.doi.org/10.1186/cc9019
UR - http://ccforum.com/content/14/3/R88
UR - http://hdl.handle.net/10044/1/80576
VL - 14
ER -