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. 2023 Oct 11:29:e941044.
doi: 10.12659/MSM.941044.

The Role of Glucose Concentration and Resveratrol in Modulating Neuroinflammatory Cytokines: Insights from an In Vitro Blood-Brain Barrier Model

Justyna Komorowska  1 , Mateusz Wątroba  2 , Małgorzata Bednarzak  2 , Anna D Grabowska  2 , Dariusz Szukiewicz  2
Affiliations

The Role of Glucose Concentration and Resveratrol in Modulating Neuroinflammatory Cytokines: Insights from an In Vitro Blood-Brain Barrier Model

Justyna Komorowska et al. Med Sci Monit. .

Abstract

BACKGROUND The prevalence of type 2 diabetes mellitus is rising, presumably because of a coexisting pandemic of obesity. Since diabetic neuropathy and neuroinflammation are frequent and significant complications of both prolonged hyperglycemia and iatrogenic hypoglycemia, the effect of glucose concentration and resveratrol (RSV) supplementation on cytokine profile was assessed in an in vitro model of the blood-brain barrier (BBB). MATERIAL AND METHODS The in vitro model of BBB was formed of endothelial cells and astrocytes, which represented the microvascular and brain compartments (MC and BC, respectively). The BC concentrations of selected cytokines - IL-10, IL-12, IL-17A, TNF-alpha, IFN-γ, GM-CSF in response to different glucose concentrations in the MC were studied. The influence of LPS in the BC and RSV in the MC on the cytokine profile in the BC was examined. RESULTS Low glucose concentration (40 mg/dL) in the MC resulted in increased concentration of all the cytokines in the BC except TNF-alpha, compared to normoglycemia-imitating conditions (90 mg/dL) (P<0.05). High glucose concentration (450 mg/dL) in the MC elevated the concentration of all the cytokines in the BC (P<0.05). RSV decreased the level of all cytokines in the BC after 24 h following its administration for all glucose concentrations in the MC (P<0.02). The greatest decline was observed in normoglycemic conditions (P<0.05). CONCLUSIONS Both hypo- and hyperglycemia-simulating conditions impair the cytokine profile in BC, while RSV can normalize it, despite relatively poor penetration through the BBB. RSV exhibits anti-neuroinflammatory effects, especially in the group with normoglycemia-simulating conditions.

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Conflict of interest statement

Conflict of interest: None declared

Figures

Figure 1
Figure 1
Effects of hyperglycemia within central nervous system. Created using Microsoft® PowerPoint® 2013 (154.0.5363.1000) MSO, Microsoft Corporation.
Figure 2
Figure 2
The cross-section scheme of in vitro model of blood–brain barrier containing co-culture of endothelial cells and astrocytes. The basement membrane with pore diameter 0.4 μm. Created using Microsoft® PowerPoint® 2013 (154.0.5363.1000) MSO, Microsoft Corporation.
Figure 3
Figure 3
The diagram illustrating the process of establishing an in vitro blood–brain model and the stages of the study. EC – endothelial cells; AC – astrocytes; MC – microvascular compartment of BBB; BC – brain compartment of BBB; LPS – lipopolysaccharide’ RSV – resveratrol. Created using Microsoft® PowerPoint® 2013 (154.0.5363.1000) MSO, Microsoft Corporation.
Figure 4
Figure 4
Mean values of cytokine concentrations (pg/ml) in brain compartment 24 h after different glucose concentrations applied in microvascular compartment. SEM – standard error of measurement (±10%). Created using Microsoft® PowerPoint® 2013 (154.0.5363.1000) MSO, Microsoft Corporation.
Figure 5
Figure 5
Mean values of cytokine concentrations (pg/ml) in brain compartment 12 h after LPS was been added to brain compartment in the 3 studied groups. In comparison, concentrations of the same cytokines in LPS-free conditions. SEM – standard error of measurement (±10%). Created using Microsoft® PowerPoint® 2013 (154.0.5363.1000) MSO, Microsoft Corporation.
Figure 6
Figure 6
Mean values of cytokine concentrations (pg/ml) in brain compartment 36 h after administration of LPS compared to 12 h after LPS administration in the 3 studied groups. SEM – standard error of measurement (±10%). Created using Microsoft® PowerPoint® 2013 (154.0.5363.1000) MSO, Microsoft Corporation.
Figure 7
Figure 7
Astrocytes from brain compartment after glucose administration. (A) Staining with hematoxylin and eosin. (B) Astrocytes from brain compartment after glucose and LPS administration. Staining with hematoxylin and eosin. No visible changes in the morphology of the astrocytes were observed. Magnification 100×. The picture was captured using LAS-X, the standard microscope imaging software from Leica Microsystems, Wetzlar, Germany.
Figure 8
Figure 8
Mean values of cytokine concentrations in brain compartment (pg/ml) 36 h after administration of LPS and 24 h after addition of RSV to the microvascular compartment. For comparison, concentrations of the same cytokines in the samples to which LPS was added and RSV was not added (control samples are marked with the letter C). SEM – standard error of measurement (±10%). Created using Microsoft® PowerPoint® 2013 (154.0.5363.1000) MSO, Microsoft Corporation.
Figure 9
Figure 9
Mean RSV concentrations (ng/ml) in the brain compartment 12 and 24 h after RSV addition to the microvascular compartment of hypo-, normo-, and hyperglycemia-simulating samples. SEM – standard error of measurement (±10%). Created using Microsoft® PowerPoint® 2013 (154.0.5363.1000) MSO, Microsoft Corporation.
Figure 10
Figure 10
Resveratrol delivery systems. Created using Microsoft® PowerPoint® 2013 (154.0.5363.1000) MSO, Microsoft Corporation.
See this image and copyright information in PMC

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