The protective effect of the blood brain barrier from systemic cytokines in an animal femur fracture model
ABSTRACT Previous studies of head trauma have shown profound release of cytokines in the brain. These changes were not expressed in peripheral tissues. The intent of this study was to take an animal model of femur fracture, monitor the expression of biochemical markers in the periphery, and compare this to their expression in the brain.
Rats were subjected to a weight-drop, femur fracture model, and then killed at various times. Samples of muscle, liver, serum, and brain were analyzed for concentrations of cytokines, and compared with controls.
Statistically significant (p < 0.05) results from the study were found in the liver. Interleukin (IL)-2, IL-10, IL-11, and other acute phase reactants were elevated at 24 hours after injury, compared with in controls. Analysis of these cytokines in the brain showed no significant increase when compared with those of controls. Further analysis also demonstrated an increase in plasma C-reactive protein and leptin in the fracture group. These results differ from our previous brain trauma study, which demonstrated no increased expression of cytokines in liver or plasma.
This animal model of peripheral injury demonstrates that there is a significant rise in acute phase reactants in liver tissue and plasma within 24 hours after injury, without a corresponding rise in cytokine concentration in the brain. These results suggest that although the brain is potentially exposed to the biochemical response to injury, the brain parenchyma itself is protected from up-regulation of proinflammatory cytokines. Interestingly, this is the opposite effect seen in our isolated brain injury study.
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ABSTRACT: Aging and neurodegenerative disease predispose to delirium and are both associated with increased activity of the innate immune system resulting in an imbalance between pro- and anti-inflammatory mediators in the brain. We examined whether hip fracture patients who develop postoperative delirium have altered levels of inflammatory mediators in cerebrospinal fluid (CSF) prior to surgery. Patients were 75 years and older and admitted for surgical repair of an acute hip fracture. CSF samples were collected preoperatively. In an exploratory study, we measured 42 cytokines and chemokines by multiplex analysis. We compared CSF levels between patients with and without postoperative delirium and examined the association between CSF cytokine levels and delirium severity. Delirium was diagnosed with the Confusion Assessment Method; severity of delirium was measured with the Delirium Rating Scale Revised-98. Mann--Whitney U tests or Student t-tests were used for between-group comparisons and the Spearman correlation coefficient was used for correlation analyses. Sixty-one patients were included, of whom 23 patients (37.7%) developed postsurgical delirium. Concentrations of Fms-like tyrosine kinase-3 (P=0.021), Interleukin-1 receptor antagonist (P=0.032) and Interleukin-6 (P=0.005) were significantly lower in patients who developed delirium postoperatively. Our findings fit the hypothesis that delirium after surgery results from a dysfunctional neuroinflammatory response: stressing the role of reduced levels of anti-inflammatory mediators in this process.Trial registration: The Effect of Taurine on Morbidity and Mortality in the Elderly Hip Fracture Patient.Registration number: NCT00497978. Local ethical protocol number: NL16222.094.07.Journal of Neuroinflammation 10/2013; 10(1):122. DOI:10.1186/1742-2094-10-122 · 4.90 Impact Factor