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Venous thromboembolism (VTE) is major health problem and is sometimes complicated by lethal pulmonary embolism (PE). Disturbances of the coagulation and anticoagulation systems are important risk factors for VTE. Comparative studies suggest that coagulation and innate immunity have a shared evolutionary origin. It is therefore unsurprising that the immune and coagulation systems are linked, with m
OBJECTIVE: We monitored hepatic lipid content (HLC) and fatty acid (FA) composition in the context of enhanced lipid handling induced by a metabolic high-fat diet (HFD) challenge and fasting.MATERIALS AND METHODS: Mice received a control diet (10% of kilocalories from fat, N = 14) or an HFD (45% or 60% of kilocalories from fat, N = 10 and N = 16, respectively) for 26 weeks. A subset of five mice r
Type 2 diabetes (T2D) is associated with deterioration of brain structure and function. Here, we tested the hypothesis that T2D induces a reorganization of the brain metabolic networks that support brain function. For that, alterations of neuronal and glial energy metabolism were investigated in a T2D model, the Goto-Kakizaki (GK) rat. (13)C magnetic resonance spectroscopy in vivo at 14.1 T was us
Environmental stress can interact with genetic predisposition to increase the risk of developing psychopathology. In this work, we tested the hypothesis that social isolation stress interacts with impaired glutathione synthesis and have cumulative effects on the neurochemical profile of the frontal cortex. A mouse model with chronic glutathione deficit induced by knockout (-/-) of the glutamate-cy
Cerebral function is associated with exceptionally high metabolic activity, and requires continuous supply of oxygen and nutrients from the blood stream. Since the mid-twentieth century the idea that brain energy metabolism is coupled to neuronal activity has emerged, and a number of studies supported this hypothesis. Moreover, brain energy metabolism was demonstrated to be compartmentalized in ne
Barbiturates, commonly used as general anaesthetics, depress neuronal activity and thus cerebral metabolism. Moreover, they are likely to disrupt the metabolic support of astrocytes to neurons, as well as the uptake of nutrients from circulation. By employing (13) C magnetic resonance spectroscopy (MRS) in vivo at high magnetic field, we characterized neuronal and astrocytic pathways of energy met
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A better understanding of BOLD responses stems from a better characterization of the brain's ability to metabolize glucose and oxygen. Non-invasive techniques such as functional magnetic resonance spectroscopy (fMRS) have thus been developed allowing for the reproducible assessment of metabolic changes during barrel cortex (S1BF) activations in rats. The present study aimed at further exploring th
Combustion and its control are essential to our existence on this planet since we knew it. Nowadays, the largest share of the world’s electricity and most of our transportation systems are powered by combustion. In addition, industrial processes also rely heavily upon combustion. In most industrial combustion systems, combustion occurs under turbulent flow conditions that can produce combustion in
Patients with diabetes display a progressive decay in the physiological counter-regulatory response to hypoglycemia, resulting in hypoglycemia unawareness. The mechanism through which the brain adapts to hypoglycemia may involve brain glycogen. We tested the hypothesis that brain glycogen supercompensation following hypoglycemia depends on blood glucose levels during recovery. Conscious rats were
Adverse environmental and social conditions early in life have a strong impact on health. They are major risk factors for mental diseases in adulthood and, in some cases, their effects can be transmitted across generations. The consequences of detrimental stress conditions on brain metabolism across generations are not well known. Using high-field (14.1 T) magnetic resonance spectroscopy, we inves
Carbon-13 nuclear magnetic resonance spectroscopy in combination with the infusion of (13)C-labeled precursors is a unique approach to study in vivo brain energy metabolism. Incorporating the maximum information available from in vivo localized (13)C spectra is of importance to get broader knowledge on cerebral metabolic pathways. Metabolic rates can be quantitatively determined from the rate of (
Many tissues exhibit metabolic compartmentation. In the brain, while there is no doubt on the importance of functional compartmentation between neurons and glial cells, there is still debate on the specific regulation of pathways of energy metabolism at different activity levels. Using (13)C magnetic resonance spectroscopy (MRS) in vivo, we determined fluxes of energy metabolism in the rat cortex
Adenosine is a neuromodulator that protects neurons from hypoxia. This effect is attributed to the ability of adenosine A1 receptors (A1 R) to inhibit excitatory synaptic transmission. However, A1 R activation also protects non-brain tissues from hypoxic insults by controlling metabolism. Thus, we now tested the hypothesis that A1 R-mediated neuroprotection after a hypoxic insult in superfused hip
BACKGROUND AND OBJECTIVE: Venous thrombosis is a common disease annually affecting 1 in 1000 individuals. The multifactorial nature of the disease is illustrated by the frequent identification of one or more predisposing genetic and/or environmental risk factors in thrombosis patients. Most of the genetic defects known today affect the function of the natural anticoagulant pathways and in particul
Reduced fibrinolytic capacity due to increased plasminogen activator inhibitor-1 (PAI-1) activity in plasma is a common finding in patients with coronary heart disease or venous thromboembolism, although its clinical significance is debated. Recently, a dimorphism in the PAI-1 promoter (4G-5G) has been reported and homozygosity for the 4G allele is associated with increased transcription and highe
BACKGROUND: Glutathione (GSH) is the major cellular redox-regulator and antioxidant. Redox-imbalance due to genetically impaired GSH synthesis is among the risk factors for schizophrenia. Here we used a mouse model with chronic GSH deficit induced by knockout (KO) of the key GSH-synthesizing enzyme, glutamate-cysteine ligase modulatory subunit (GCLM).METHODS: With high-resolution magnetic resonanc
A new method to determine the concentration of the free protein S in plasma is described. It is an enzyme-linked ligandsorbent assay (ELSA) which utilises the protein S binding capacity of the natural ligand C4b-binding protein (C4BP) to capture the free protein S from plasma samples. The use of C4BP as ligand in the assay is possible due to the high affinity (Kd = 0.1 nM) of the interaction betwe
The neurochemical profile of the cortex develops in a region and time specific manner, which can be distorted by psychiatric and other neurological pathologies. Pre-clinical studies often involve experimental mouse models. In this study, we determined the neurochemical profile of C57BL/6 mice in a longitudinal study design to provide a reference frame for the normal developing mouse cortex. Using
