Attenuation of chronic tension headache frequency and severity with daily L-arginine and aged garlic extract dietary supplementation.

A 74-year-old female subject with suboptimal management of episodic tension headache was treated with a daily dose of 1.5 g L-arginine and 1.2 g aged garlic extract (AGE).

Automated Quantitative Analysis of Blood-Brain Barrier Permeability Using Intellesis Machine-Learning.

Background: An increase in blood brain barrier permeability commonly precedes neuro-inflammation and cognitive impairment in models of dementia. Common methods to estimate capillary permeability have potential confounders, or require laborious and subjective semi-manual analysis.

New Method: Here we used snap frozen mouse and rat brain sections that were double-immunofluorescent labeled for immunoglobulin G (IgG; plasma protein) and laminin-α4 (capillary basement membrane).

A Systematic Review of the MDMA Model to Address Social Impairment in Autism.

Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterised by repetitive behaviours, cognitive rigidity/inflexibility, and social-affective impairment. Unfortunately, no gold-standard treatments exist to alleviate the core socio-behavioural impairments of ASD. Meanwhile, the prosocial empathogen/entactogen 3,4-methylene-dioxy-methamphetamine (MDMA) is known to enhance sociability and empathy in both humans and animal models of psychological disorders.

Sodium alginate capsulation increased brain delivery of probucol and suppressed neuroinflammation and neurodegeneration.

Aim: To enhance the bioavailability and brain uptake of probucol and examine whether it attenuates neuroinflammation and neurodegeneration by utilizing a sodium alginate nanoencapsulation technique.

Materials & Methods: Wild-type mice were given either low-fat standard chow, high-fat (HF) diet to induce neuroinflammation and neurodegeneration, HF diet supplemented with nanocapsuled probucol at a concentration of 0.1% (w/w), HF diet supplemented with noncapsulated probucol at the same concentration of 0.

Probucol prevents blood-brain barrier dysfunction and cognitive decline in mice maintained on pro-diabetic diet.

An emerging body of evidence consistently suggests that compromised blood-brain barrier integrity may be causally associated with cognitive decline induced by type-2 diabetes. Our previous studies demonstrated that selected anti-inflammatory/anti-oxidative agents can preserve the integrity of blood-brain barrier and prevent neuroinflammation in mouse models of dysfunctional blood-brain barrier. Therefore, we have tested whether the previously proven blood-brain barrier protective agent, probucol, can prevent blood-brain barrier breakdown and cognitive decline in a dietary-induced murine model of diabetic insulin resistance.

A Multimodal Spectroscopic Imaging Method To Characterize the Metal and Macromolecular Content of Proteinaceous Aggregates ("Amyloid Plaques").

Alzheimer's disease (AD) is a major international health and economic concern. A key pathological feature of AD is so-called "amyloid-β-plaques", or "Aβ-plaques", which are deposits of aggregated protein, enriched with the Aβ fragment of amyloid precursor protein. Despite their name, the deposits are not pure Aβ and have a heterogeneous, chemically complex composition that can include multiple proteins, lipids, and metal ions (Fe, Cu, or Zn).

Dietary fat and physiological determinants of plasma chylomicron remnant homoeostasis in normolipidaemic subjects: insight into atherogenic risk.

TAG depleted remnants of postprandial chylomicrons are a risk factor for atherosclerosis. Recent studies have demonstrated that in the fasted state, the majority of chylomicrons are small enough for transcytosis to arterial subendothelial space and accelerate atherogenesis. However, the size distribution of chylomicrons in the absorptive state is unclear.

Differential regulation of sphingolipid metabolism in plasma, hippocampus, and cerebral cortex of mice administered sphingolipid modulating agents.

Accumulation of ceramide is implicated in mediating the cellular responses to stress and aberrant sphingolipid metabolism is frequently associated with metabolic and neurodegenerative diseases. It is often assumed that (i) peripheral disturbances in sphingolipid concentrations are reflective of processes occurring in the brain, or (ii) circulating sphingolipids directly influence cerebral sphingolipid abundance. In order to address these assumptions, this study explores, in a physiological system, the metabolic pathways regulating sphingolipid metabolism in the brain and plasma of mice.

The Effects of Long-Term Saturated Fat Enriched Diets on the Brain Lipidome.

The brain is highly enriched in lipids, where they influence neurotransmission, synaptic plasticity and inflammation. Non-pathological modulation of the brain lipidome has not been previously reported and few studies have investigated the interplay between plasma lipid homeostasis relative to cerebral lipids. This study explored whether changes in plasma lipids induced by chronic consumption of a well-tolerated diet enriched in saturated fatty acids (SFA) was associated with parallel changes in cerebral lipid homeostasis.

Plasma triglyceride and high density lipoprotein cholesterol are poor surrogate markers of pro-atherogenic chylomicron remnant homeostasis in subjects with the metabolic syndrome.

Background: Subjects with metabolic syndrome (MetS) exhibit impaired lipoprotein metabolism and have an increased risk of cardiovascular disease. Although the risk is attributed primarily to the risk associated with individual components, it is also likely affected by other associated metabolic defects. Remnants of postprandial lipoproteins show potent atherogenicity in cell and animal models of insulin resistance and in pre-diabetic subjects with postprandial dyslipidemia.

The Association of Vitamin D Status with Dyslipidaemia and Biomarkers of Endothelial Cell Activation in Older Australians.

Background/aims: Vitamin D has been investigated for many non-skeletal effects. The objective of this study was to determine whether circulating lipids, systemic inflammation, and biomarkers of endothelial cell activation varied with the vitamin D status of older Australians.

Methods: One hundred and one participants were proportionately and randomly sampled across tertiles of 25 hydroxy vitamin D (25(OH)D) from a larger cohort of free living older adults (T1 median = 97; T2 median = 74.

Hypertriglyceridemic subjects exhibit an accumulation of small dense chylomicron particles in the fasting state.

Aim: Normocholesterolemic subjects with elevated fasting plasma triglycerides are at increased risk of atherosclerosis through mechanisms that are not yet delineated. We hypothesized that elevated plasma triglyceride is associated with increased vascular exposure to pro-atherogenic lipoprotein remnants. To test this hypothesis, the abundance, and size distribution of chylomicron particles were determined in individuals with and without hypertriglyceridemia.

Serum 25-hydroxyvitamin D is associated with reduced verbal episodic memory in healthy, middle-aged and older adults.

Background: There is increasing evidence supporting an association of higher serum vitamin D concentration with better cognitive performance in older individuals. However, to date, consideration of the putative association between vitamin D and cognition has been based principally on studies investigating clinical participant samples manifesting vitamin D deficiency, particularly in older people. Moreover, relationships between vitamin D and cognition are typically not considered in the context of counter-regulatory calcium-modulating hormones or calcium homeostasis.

The vitamin D, ionised calcium and parathyroid hormone axis of cerebral capillary function: therapeutic considerations for vascular-based neurodegenerative disorders.

Blood-brain barrier dysfunction characterised by brain parenchymal extravasation of plasma proteins may contribute to risk of neurodegenerative disorders, however the mechanisms for increased capillary permeability are not understood. Increasing evidence suggests vitamin D confers central nervous system benefits and there is increasing demand for vitamin D supplementation. Vitamin D may influence the CNS via modulation of capillary function, however such effects may be indirect as it has a central role in maintaining calcium homeostasis, in concert with calcium regulatory hormones.

Blood-brain barrier dysfunction developed during normal aging is associated with inflammation and loss of tight junctions but not with leukocyte recruitment.

Background: Functional loss of blood-brain barrier (BBB) is suggested to be pivotal to pathogenesis and pathology of vascular-based neurodegenerative disorders such as Alzheimer's disease. We recently reported in wild-type mice maintained on standard diets, progressive deterioration of capillary function with aging concomitant with heightened neuroinflammation. However, the mice used in this study were relatively young (12 months of age) and potential mechanisms for loss of capillary integrity were not investigated per se.

Nicotine Attenuates Disruption of Blood-Brain Barrier Induced by Saturated-Fat Feeding in Wild-Type Mice.

Introduction: Emerging evidence suggests that integrity of blood-brain barrier (BBB) is pivotal to pathology and pathogenesis of vascular-based neurodegenerative disorders. We have recently reported BBB protective effects of nutraceutical agents with anti-inflammatory properties in an established dietary-induced BBB dysfunction model. Studies also reported that nicotine exhibits anti-oxidative/-inflammatory effects and improve cognitive impairment in Alzheimer's disease.

Long-term probucol therapy continues to suppress markers of neurovascular inflammation in a dietary induced model of cerebral capillary dysfunction.

Background: Probucol has been shown to prevent cerebral capillary disturbances characterized by blood-to-brain extravasation of plasma derived proteins and neurovascular inflammation in mice maintained on western-styled diets for 12 weeks. However the effect of probucol on capillary integrity in aging models with capillary dysfunction is not known.

Methods: Wild-type C57BL6 mice were randomized to a low-fat (LF); saturated-fat (SFA); or SFA + Probucol diet for up to12 months of intervention.

Neuropsychological performance is positively associated with plasma albumin in healthy adults.

Background: Albumin serves a range of physiological functions that are vital to overall brain and cognitive health. Indeed, associations between cognitive performance and albumin have been demonstrated in individuals with chronic liver or kidney disease and in patients with a high urinary excretion of albumin. However, an association of plasma albumin with cognitive performance has not been reported in otherwise healthy participants with clinically acceptable plasma albumin concentrations.

The Serum Concentration of the Calcium Binding Protein S100B is Positively Associated with Cognitive Performance in Older Adults.

S100B is a calcium binding peptide produced predominantly by astroglial cells in the central nervous system. S100B paradoxically has neurotrophic and apoptotic effects, dependent on extracellular concentration. This study investigated the relationship between serum S100B levels and neuropsychological performance across a range of cognitive domains in healthy older aged adults.

Nutraceutical agents with anti-inflammatory properties prevent dietary saturated-fat induced disturbances in blood-brain barrier function in wild-type mice.

Background: Emerging evidence suggests that disturbances in the blood-brain barrier (BBB) may be pivotal to the pathogenesis and pathology of vascular-based neurodegenerative disorders. Studies suggest that heightened systemic and central inflammations are associated with BBB dysfunction. This study investigated the effect of the anti-inflammatory nutraceuticals garlic extract-aged (GEA), alpha lipoic acid (ALA), niacin, and nicotinamide (NA) in a murine dietary-induced model of BBB dysfunction.

Adjustment of ionized calcium concentration for serum pH is not a valid marker of calcium homeostasis: implications for identifying individuals at risk of calcium metabolic disorders.

Background: Ionized calcium (iCa) is the biologically active form of this micronutrient. Serum determination of iCa is measured via ion-electrode potentiometry (IEP) and reporting iCa relative to pH 7.4 is normally utilized to avoid the potential confounding effects of ex vivo changes to serum pH.

Probucol prevents blood-brain barrier dysfunction in wild-type mice induced by saturated fat or cholesterol feeding.

Dysfunction of the blood-brain barrier (BBB) is an early pathological feature of vascular dementia and Alzheimer's disease (AD) and is triggered by inflammatory stimuli. Probucol is a lipid-lowering agent with potent anti-oxidant properties once commonly used for the treatment of cardiovascular disease. Probucol therapy was found to stabilize cognitive symptoms in elderly AD patients, whereas in amyloid transgenic mice probucol was shown to attenuate amyloidosis.

ApoA-1 infusion reduces arterial cholesterol and myocardial lesions in a rat model of cardiac dysfunction and insulin resistance.

Objective: Low plasma high-density lipoprotein cholesterol (HDL-C) concentration is associated with the metabolic syndrome (MetS) and increased prevalence of cardiovascular disease (CVD). Animal and human studies report infusion of apolipoprotein A-1 (apoA-1) can reduce endothelial dysfunction, and/or induce regression of atherosclerosis. However, the direct mechanisms underlying the vascular benefits of either apoA-1 or HDL-C remain unclear.

The chronic effects of fish oil with exercise on postprandial lipaemia and chylomicron homeostasis in insulin resistant viscerally obese men.

Background: Visceral obesity and insulin resistance are associated with a postprandial accumulation of atherogenic chylomicron remnants that is difficult to modulate with lipid-lowering therapies. Dietary fish oil and exercise are cardioprotective interventions that can significantly modify the metabolism of TAG-rich lipoproteins. In this study, we investigated whether chronic exercise and fish oil act in combination to affect chylomicron metabolism in obese men with moderate insulin resistance.