Thyroid hormone status defines brown adipose tissue activity and browning of white adipose tissues in mice

The present study aimed to determine the effect of thyroid hormone dysfunction on brown adipose tissue activity and white adipose tissue browning in mice. Twenty randomized female C57BL/6NTac mice per treatment group housed at room temperature were rendered hypothyroid or hyperthyroid. In-vivo small animal 18F-FDG PET/MRI was performed to determine the effects of hypo- and hyperthyroidism on BAT mass and BAT activity. Ex-vivo14C-acetate loading assay and assessment of thermogenic gene and protein expression permitted analysis of oxidative and thermogenic capacities of WAT and BAT of eu-, hyper and hypothyroid mice. 18F-FDG PET/MRI revealed a lack of brown adipose tissue activity in hypothyroid mice, whereas hyperthyroid mice displayed increased BAT mass alongside enhanced 18F-FDG uptake. In white adipose tissue of both, hyper- and hypothyroid mice, we found a significant induction of thermogenic genes together with multilocular adipocytes expressing UCP1. Taken together, these results suggest that both the hyperthyroid and hypothyroid state stimulate WAT thermogenesis most likely as a consequence of enhanced adrenergic signaling or compensation for impaired BAT function, respectively

Hypothesis and theory : a pathophysiological concept of stroke-induced acute phase response and increased intestinal permeability leading to secondary brain damage

Gut integrity impairment leading to increased intestinal permeability (IP) is hypothesized to be a trigger of critically illness. Approximately 15–20% of human ischemic stroke (IS) victims require intensive care, including patients with impaired level of consciousness or a high risk for developing life-threatening cerebral edema. Local and systemic inflammatory reactions are a major component of the IS pathophysiology and can significantly aggravate brain tissue damage. Intracerebral inflammatory processes following IS have been well studied. Until now, less is known about systemic inflammatory responses and IS consequences apart from a frequently observed post-IS immunosuppression. Here, we provide a hypothesis of a crosstalk between systemic acute phase response (APR), IP and potential secondary brain damage during acute and subacute IS stages supported by preliminary experimental data. Alterations of the acute phase proteins (APPs) C-reactive protein and lipopolysaccharide-binding protein and serum level changes of antibodies directed against Escherichia coli-cell extract antigen (IgA-, IgM-, and IgG-anti-E. coli) were investigated at 1, 2, and 7 days following IS in ten male sheep. We found an increase of both APPs as well as a decrease of all anti-E. coli antibodies within 48 h following IS. This may indicate an early systemic APR and increased IP, and underlines the importance of the increasingly recognized gut-brain axis and of intestinal antigen release for systemic immune responses in acute and subacute stroke stages

Hypothesis and Theory: A Pathophysiological Concept of Stroke-Induced Acute Phase Response and Increased Intestinal Permeability Leading to Secondary Brain Damage

Gut integrity impairment leading to increased intestinal permeability (IP) is hypothesized to be a trigger of critically illness. Approximately 15–20% of human ischemic stroke (IS) victims require intensive care, including patients with impaired level of consciousness or a high risk for developing life-threatening cerebral edema. Local and systemic inflammatory reactions are a major component of the IS pathophysiology and can significantly aggravate brain tissue damage. Intracerebral inflammatory processes following IS have been well studied. Until now, less is known about systemic inflammatory responses and IS consequences apart from a frequently observed post- IS immunosuppression. Here, we provide a hypothesis of a crosstalk between systemic acute phase response (APR), IP and potential secondary brain damage during acute and subacute IS stages supported by preliminary experimental data. Alterations of the acute phase proteins (APPs) C-reactive protein and lipopolysaccharide-binding protein and serum level changes of antibodies directed against Escherichia coli-cell extract antigen (IgA-, IgM-, and IgG-anti-E. coli) were investigated at 1, 2, and 7 days following IS in ten male sheep. We found an increase of both APPs as well as a decrease of all anti- E. coli antibodies within 48 h following IS. This may indicate an early systemic APR and increased IP, and underlines the importance of the increasingly recognized gut-brain axis and of intestinal antigen release for systemic immune responses in acute and subacute stroke stages

Cerebral blood flow measurement with oxygen-15 water positron emission tomography

The human brain receives approximately 15 % of the cardiac output and therefore is the most demanding organ in respect to blood flow supply. This fact emphasizes the importance of perfusion as a key factor in a variety of cerebrovascular and other diseases including stroke, migraine, and brain tumors. Today, numerous imaging techniques are able to visualize brain perfusion, but only few of them provide quantitative information. In the field of modern in vivo imaging techniques, positron emission tomography (PET) is considered to be the gold standard to give reliable results about major aspects of cerebral physiology. [15O]H2O allows for quantitative cerebral blood flow (CBF) measurement within a few minutes, and subsequent 15O imaging can provide precise information on oxygen metabolism like cerebral oxygen metabolism and oxygen extraction fraction. As a result, PET has become an extremely useful research tool for defining cerebral blood flow and physiology. However, complex methodological logistics and a limited availability of the imaging system hamper the widespread use of CBF PET in clinical routine. The chapter aims at summarizing the radiosynthesis, data acquisition, and analysis, as well as major preclinical and clinical applications of [15O]H2O PET

Cerebral blood flow measurement with oxygen-15 water positron emission tomography

The human brain receives approximately 15% of the cardiac output and therefore is the most demanding organ in respect to blood flow supply. This fact emphasizes the importance of perfusion as a key factor in a variety of cerebrovascular and other diseases including stroke, migraine, and brain tumors. Today, numerous imaging techniques are able to visualize brain perfusion, but only few of them provide quantitative information. In the field of modern in vivo imaging techniques, positron emission tomography (PET) is considered to be the gold standard to give reliable results about major aspects of cerebral physiology. [15O]H2O allows for quantitative cerebral blood flow (CBF) measurement within a few minutes, and subsequent 15O[O2] imaging can provide precise information on oxygen metabolism like cerebral oxygen metabolism and oxygen extraction fraction. As a result, PET has become an extremely useful research tool for defining cerebral blood flow and physiology. However, complex methodological logistics and a limited availability of the imaging system hamper the widespread use of CBF PET in clinical routine. The chapter aims at summarizing the radiosynthesis, data acquisition, and analysis, as well as major preclinical and clinical applications of [15O]H2O PET

Fully automated calculation of image-derived input function in simultaneous PET/MRI in a sheep model

Background Obtaining the arterial input function (AIF) from image data in dynamic positron emission tomography (PET) examinations is a non-invasive alternative to arterial blood sampling. In simultaneous PET/magnetic resonance imaging (PET/MRI), high-resolution MRI angiographies can be used to define major arteries for correction of partial-volume effects (PVE) and point spread function (PSF) response in the PET data. The present study describes a fully automated method to obtain the image-derived input function (IDIF) in PET/MRI. Results are compared to those obtained by arterial blood sampling. Methods To segment the trunk of the major arteries in the neck, a high-resolution time-of-flight MRI angiography was postprocessed by a vessel-enhancement filter based on the inertia tensor. Together with the measured PSF of the PET subsystem, the arterial mask was used for geometrical deconvolution, yielding the time-resolved activity concentration averaged over a major artery. The method was compared to manual arterial blood sampling at the hind leg of 21 sheep (animal stroke model) during measurement of blood flow with O15-water. Absolute quantification of activity concentration was compared after bolus passage during steady state, i.e., between 2.5- and 5-min post injection. Cerebral blood flow (CBF) values from blood sampling and IDIF were also compared. Results The cross-calibration factor obtained by comparing activity concentrations in blood samples and IDIF during steady state is 0.98 ± 0.10. In all examinations, the IDIF provided a much earlier and sharper bolus peak than in the time course of activity concentration obtained by arterial blood sampling. CBF using the IDIF was 22 % higher than CBF obtained by using the AIF yielded by blood sampling. Conclusions The small deviation between arterial blood sampling and IDIF during steady state indicates that correction of PVE and PSF is possible with the method presented. The differences in bolus dynamics and, hence, CBF values can be explained by the different sampling locations (hind leg vs. major neck arteries) with differences in delay/dispersion. It will be the topic of further work to test the method on humans with the perspective of replacing invasive blood sampling by an IDIF using simultaneous PET/MRI

Hypothesis and Theory: A Pathophysiological Concept of Stroke-Induced Acute Phase Response and Increased Intestinal Permeability Leading to Secondary Brain Damage

Gut integrity impairment leading to increased intestinal permeability (IP) is hypothesized to be a trigger of critically illness. Approximately 15–20% of human ischemic stroke (IS) victims require intensive care, including patients with impaired level of consciousness or a high risk for developing life-threatening cerebral edema. Local and systemic inflammatory reactions are a major component of the IS pathophysiology and can significantly aggravate brain tissue damage. Intracerebral inflammatory processes following IS have been well studied. Until now, less is known about systemic inflammatory responses and IS consequences apart from a frequently observed post- IS immunosuppression. Here, we provide a hypothesis of a crosstalk between systemic acute phase response (APR), IP and potential secondary brain damage during acute and subacute IS stages supported by preliminary experimental data. Alterations of the acute phase proteins (APPs) C-reactive protein and lipopolysaccharide-binding protein and serum level changes of antibodies directed against Escherichia coli-cell extract antigen (IgA-, IgM-, and IgG-anti-E. coli) were investigated at 1, 2, and 7 days following IS in ten male sheep. We found an increase of both APPs as well as a decrease of all anti- E. coli antibodies within 48 h following IS. This may indicate an early systemic APR and increased IP, and underlines the importance of the increasingly recognized gut-brain axis and of intestinal antigen release for systemic immune responses in acute and subacute stroke stages

Hypothesis and Theory: A Pathophysiological Concept of Stroke-Induced Acute Phase Response and Increased Intestinal Permeability Leading to Secondary Brain Damage

Gut integrity impairment leading to increased intestinal permeability (IP) is hypothesized to be a trigger of critically illness. Approximately 15–20% of human ischemic stroke (IS) victims require intensive care, including patients with impaired level of consciousness or a high risk for developing life-threatening cerebral edema. Local and systemic inflammatory reactions are a major component of the IS pathophysiology and can significantly aggravate brain tissue damage. Intracerebral inflammatory processes following IS have been well studied. Until now, less is known about systemic inflammatory responses and IS consequences apart from a frequently observed post- IS immunosuppression. Here, we provide a hypothesis of a crosstalk between systemic acute phase response (APR), IP and potential secondary brain damage during acute and subacute IS stages supported by preliminary experimental data. Alterations of the acute phase proteins (APPs) C-reactive protein and lipopolysaccharide-binding protein and serum level changes of antibodies directed against Escherichia coli-cell extract antigen (IgA-, IgM-, and IgG-anti-E. coli) were investigated at 1, 2, and 7 days following IS in ten male sheep. We found an increase of both APPs as well as a decrease of all anti- E. coli antibodies within 48 h following IS. This may indicate an early systemic APR and increased IP, and underlines the importance of the increasingly recognized gut-brain axis and of intestinal antigen release for systemic immune responses in acute and subacute stroke stages