Obesity Exacerbates Sepsis‐Induced Inflammation and Microvascular Dysfunction in Mouse Brain

Abstract

These findings suggest that the increased morbidity to sepsis in obesity may result from exaggerated microvascular inflammatory and thrombogenic responses that include the activation of endothelial cells with subsequent expression of adhesion molecules, such as P-selectin.

Increased Brain Microvascular MMP-9 and Incidence of Haemorrhagic Transformation in Obese Mice after Experimental Stroke

“…Conventional risk factors for HT include hyperglycaemia and hypertension (Paciaroni et al, 2008), both of which are common in obese subjects. However, these factors are unlikely to account for the increased frequency of HT in the present study, because pre-ischaemic blood glucose levels were similar in lean and obese mice, and previous studies have not found significant differences in blood pressure (Vachharajani et al, 2005). Thrombolytic treatment also predisposes to HT (Zhao et al, 2007).…”

The association between body-mass index and patient outcome in septic shock: a retrospective cohort study

“…Initial data indicated that obesity is a risk factor for the development of sepsis and septic shock [6], and obese patients with sepsis have been reported to have higher mortality rates than their lean counterparts [7]. Experimental models have provided evidence that obesity may exacerbate sepsis-induced inflammation and microvascular dysfunction in the intestinal tract and brain of rodents [8,9]. Nevertheless, it is unknown whether body mass and commonly defined weight categories have an influence on septic shock mortality in humans.…”

“…Von allen Patienten wurde der BMI, demographische, klinische und laborchemische Parameter gemeinsam mit Outcomevariabeln dokumentiert. Die Studienpatienten wurden wie folgt anhand des BMI kategorisiert: BMI < 18,5 kg/m², Untergewicht; BMI 18,[5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24]9 kg/m², Normalgewicht;9 kg/m², Übergewicht; BMI > 30 kg/m², Fettleibigkeit. Bivariate und multivariate logistische Regressionsmodelle wurden verwendet, um den Zusammenhang zwischen dem BMI und Outcomevariabeln zu untersuchen.…”

Phenotypic Heterogeneity of the Endothelium

“…77 Cecal ligation puncture in mice resulted in increased P-selectin protein expression in brain, kidney, stomach, small bowel, and large bowel, an effect that was greatly accentuated in obese animals. 81 In a mouse model of sickle cell disease, constitutive expression of P-selectin was increased in several tissues, whereas E-selectin was increased in only the penis. 82 Interestingly, inflammatory mediators such as interleukin-1 and TNF-␣ induce P-selectin mRNA expression in mice, but not primates, 83 underscoring the importance of interspecies differences in transcriptional control.…”