The effect of systemic inflammation on human brain barrier function

Elwood, Elliot; Lim, Zhi Wei; Naveed, Hammad; Galea, Ian

doi:10.1016/j.bbi.2016.10.020

Cited by 96 publications

(87 citation statements)

References 30 publications

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“…Future studies may use DCE‐MRI to explore (1) physiological variation in BBB function related to variables such as age (Elwood et al . ) or sex (Maggioli et al . ); (2) BBB changes in pathology; (3) the effect of different physiological states on the BBB; and (4) the evaluation of pharmacological agents which prevent or reverse BBB disruption.…”

Section: Discussionmentioning

confidence: 99%

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Blood–brain barrier permeability measured using dynamic contrast‐enhanced magnetic resonance imaging: a validation study

Varatharaj

Liljeroth

Darekar

et al. 2018

The Journal of Physiology

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Key points The blood–brain barrier (BBB) is an important and dynamic structure which contributes to homeostasis in the central nervous system.BBB permeability changes occur in health and disease but measurement of BBB permeability in humans is not straightforward.Dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) can be used to model the movement of gadolinium contrast into the brain, expressed as the influx constant K i.Here evidence is provided that K i as measured by DCE‐MRI behaves as expected for a marker of overall BBB leakage.These results support the use of DCE‐MRI for in vivo studies of human BBB permeability in health and disease. AbstractBlood–brain barrier (BBB) leakage can be measured using dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) as the influx constant K i. To validate this method we compared measured K i with biological expectations, namely (1) higher K i in healthy individual grey matter (GM) versus white matter (WM), (2) GM/WM cerebral blood volume (CBV) ratio close to the histologically established GM/WM vascular density ratio, (3) higher K i in visibly enhancing multiple sclerosis (MS) lesions versus MS normal appearing white matter (NAWM), and (4) higher K i in MS NAWM versus healthy individual NAWM. We recruited 13 healthy individuals and 12 patients with MS and performed whole‐brain 3D DCE‐MRI at 3 T. K i and CBV were calculated using Patlak modelling for manual regions of interest (ROI) and segmented tissue masks. K i was higher in control GM versus WM (P = 0.001). CBV was higher in GM versus WM (P = 0.005, mean ratio 1.9). K i was higher in visibly enhancing MS lesions versus MS NAWM (P = 0.002), and in MS NAWM versus controls (P = 0.014). Bland–Altman analysis showed no significant difference between ROI and segmentation methods (P = 0.638) and an intra‐class correlation coefficient showed moderate single measure consistency (0.610). K i behaves as expected for a compound marker of permeability and surface area. The GM/WM CBV ratio measured by this technique is in agreement with the literature. This adds evidence to the validity of K i measured by DCE‐MRI as a marker of overall BBB leakage.

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Section: Discussionmentioning

confidence: 99%

“…BBB permeability is a physiological phenomenon, present in the healthy state; however, it increases with age and in disease (Elwood et al . ). Measuring BBB permeability in humans is not straightforward.…”

Section: Introductionmentioning

confidence: 97%

Blood–brain barrier permeability measured using dynamic contrast‐enhanced magnetic resonance imaging: a validation study

Varatharaj

Liljeroth

Darekar

et al. 2018

The Journal of Physiology

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“…Related to the genesis and worsening of these is the increased blood-brain barrier (BBB) permeability, an endothelial structure which controls the influx and efflux of components between blood flow and central nervous system (CNS) (Abbott 2000). Low chronic systemic inflammation during aging, known as 'inflammaging', has been proposed to increase BBB permeability (Elwood et al 2017), which has been measured through peripheral levels of neuronalderived proteins, such as S100β and neuronal-specific enolase (NSE) (Marchi et al 2004, Sağ et al 2017). S100β protein is composed by two isometric subunits being expressed primarily by astrocytes and found predominately in astroglial and Scwann cells, while NSE is a 78kD gammahomodimer that represents the mainly enolase-enzyme found in neurons , Haque et al 2016.…”

Section: Introductionmentioning

confidence: 99%

Exercise and taurine in inflammation, cognition, and peripheral markers of blood-brain barrier integrity in older women

Chupel

Minuzzi

Furtado

et al. 2018

Appl. Physiol. Nutr. Metab.

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1Exercise and taurine in inflammation, cognition, and peripheral markers of blood-brain barrier integrity in older women Authors:Matheus Abstract:Immunosenescence contribute to increase the blood-brain barrier (BBB) permeability, leading cognitive impairment and neurodegeneration. Thus, we investigated the anti-inflammatory effect of exercise and taurine supplementation on peripheral markers of blood-brain barrier, inflammation, and cognition of elderly women. Forty-eight elderly women (83.58±6.9 years) participated in the study, and were allocated into combined exercise training (CET: n=13), taurine supplementation (TAU: n=12), exercise training associated with taurine (CET+TAU: n=11), or control group (CG: n=12). Exercise was applied twice a week (multi-modal exercise). Taurine ingestion was 1.5g., once a day. Participants were evaluated before and after 14-weeks of intervention. Plasma levels of IL-1β, IL-1ra, IL-6, IL-10, IL-17, TNF-α, and serum concentration of S100β and neuron specific enolase (NSE) were determined. The mini mental state examination (MMSE) was also applied.Concentrations of S100β were maintained in all intervention groups, while a subtle increase in the CG was found. NSE levels increased only in TAU group (p<0.05). CET reduced TNF-α, IL-6, and IL-1β/IL-1ra, IL-6/IL10, TNF-α/IL-10 ratios (p<0.05). TAU decreased the IL-1β/IL-1ra ratio (p<0.05). MMSE score increased only in CET+TAU group (p<0.05). Multiple regression analysisshowed that there was a trend for changes in IL-1β and CCI to be independently associated with changes in S100β. Exercise and taurine decreased inflammation, and maintained the BBB integrity in elderly women. Exercise emerged as an important tool to improve brain health even when started at advanced ages.

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“…Trajectory of serum CRP levels from baseline (preoperatively) to postoperative days 1 through 5. Finally, animal and human studies show that CRP (in a clinically plausible range of 10-20 μg/mL) can induce blood-brain disruption especially in patients with preexistent brain pathology [54][55][56]. The solid line depicts the median value of CRP leves in patients (N = 34 to 41, varying to the number of available samples).…”

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confidence: 99%

The trajectory of C‐reactive protein serum levels in older hip fracture patients with postoperative delirium

Slor

Witlox

Adamis

et al. 2019

Int J Geriat Psychiatry

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Objectives Important precipitating risk factors for delirium such as infections, vascular disorders, and surgery are accompanied by a systemic inflammatory response. Systemic inflammatory mediators can induce delirium in susceptible individuals. Little is known about the trajectory of systemic inflammatory markers and their role in the development and outcome of delirium. Methods This is a prospective cohort study of older patients undergoing acute surgery for hip fracture. Baseline characteristics were assessed preoperatively. During hospital admission, presence of delirium was assessed daily according to the Confusion Assessment Method criteria. This study compared the trajectory of serum levels of the C‐reactive protein (CRP) between people with and without postoperative delirium. Blood samples were taken at baseline and at postoperative day 1 through postoperative day 5. Results Forty‐one out of 121 patients developed postoperative delirium after hip fracture surgery. Longitudinal analysis of the trajectory of serum CRP levels using the Generalized Estimating Equations (GEE) method identified that higher CRP levels were associated with postoperative delirium. CRP levels were higher from postoperative day 2 through postoperative day 5. No significant differences in serum CRP levels were found when we compared patients with short (1‐2 days) and more prolonged delirium (3 days or more). Conclusions Delirium is associated with an increased systemic inflammatory response, and our results suggest that CRP plays a role in the underlying (inflammatory‐vascular) pathological pathway of postoperative delirium.

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The effect of systemic inflammation on human brain barrier function

Cited by 96 publications

References 30 publications

Blood–brain barrier permeability measured using dynamic contrast‐enhanced magnetic resonance imaging: a validation study

Blood–brain barrier permeability measured using dynamic contrast‐enhanced magnetic resonance imaging: a validation study

Exercise and taurine in inflammation, cognition, and peripheral markers of blood-brain barrier integrity in older women

The trajectory of C‐reactive protein serum levels in older hip fracture patients with postoperative delirium

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