Metabolic dysfunction-associated steatotic liver disease is associated with effects on cerebral perfusion and white matter integrity.

It is unclear whether early metabolic and inflammatory aberrations in the liver are associated with detrimental changes in brain structure and cognitive function. This cross-sectional study examines putative associations between metabolic dysfunction-associated steatotic liver disease (MASLD) and brain health in 36-55 year-old participants with obesity (n = 70) from the BARICO study (BAriatric surgery Rijnstate and Radboudumc neuroImaging and Cognition in Obesity). The participants underwent brain magnetic resonance imaging to study brain volumes and cortical thickness (3T MRI including T1-weighted magnetization-prepared rapid gradient-echo sequence), cerebral blood perfusion (arterial spin labeling) and white matter integrity (diffusion weighted imaging to assess mean-skeletonized mean diffusivity and fluid-attenuated inversion recovery to detect the presence of white matter hyperintensities (WMH)).

Deep learning-based segmentation in MRI-(immuno)histological examination of myelin and axonal damage in normal-appearing white matter and white matter hyperintensities.

The major vascular cause of dementia is cerebral small vessel disease (SVD). Its diagnosis relies on imaging hallmarks, such as white matter hyperintensities (WMH). WMH present a heterogenous pathology, including myelin and axonal loss.

Impact of Microbiota and Metabolites on Intestinal Integrity and Inflammation in Severe Obesity.

Obesity is a multifactorial disease associated with low-grade inflammation. The gut is thought to be involved in obesity-related inflammation, as it is continuously exposed to antigens from food, microbiota and metabolites. However, the exact underlying mechanisms are still unknown.

Additive effects of depression and obesity on neural correlates of inhibitory control.

Background: Depression and obesity are associated with impaired inhibitory control. Behavioral evidence indicates an exacerbating additive effect when both conditions co-occur. However, the underlying neural mechanisms remain unclear.

Three-dimensional identification of microvascular pathology and neurovascular inflammation in severe white matter hyperintensity: a case report.

White matter hyperintensities (WMH) are the most prevalent markers of cerebral small vessel disease (SVD), which is the major vascular risk factor for dementia. Microvascular pathology and neuroinflammation are suggested to drive the transition from normal-appearing white matter (NAWM) to WMH, particularly in individuals with hypertension. However, current imaging techniques cannot capture ongoing NAWM changes.

Long-Term Brain Structure and Cognition Following Bariatric Surgery.

Importance: Weight loss induced by bariatric surgery (BS) is associated with improved cognition and changed brain structure; however, previous studies on the association have used small cohorts and short follow-up periods, making it difficult to determine long-term neurological outcomes associated with BS.

Objective: To investigate long-term associations of weight loss after BS with cognition and brain structure and perfusion.

Design, Setting, And Participants: This cohort study included participants from the Bariatric Surgery Rijnstate and Radboudumc Neuroimaging and Cognition in Obesity study.

Cognitive Control and Weight Loss After Bariatric Surgery: the BARICO Study.

Background And Objectives: Bariatric surgery (BS) is an effective treatment for obesity. However, some individuals experience insufficient weight loss after surgery. Therefore, we investigated whether cognitive control affects weight loss after Roux-en-Y gastric bypass (RYGB).

Factors Associated With Cognitive Improvement After Bariatric Surgery Among Patients With Severe Obesity in the Netherlands.

Importance: Bariatric surgery-induced weight loss is often associated with improved cognitive function. However, improvement in cognitive function is not always exhibited by all patients, and the mechanisms behind cognitive improvement remain unknown.

Objective: To investigate the association of changes in adipokines, inflammatory factors, mood, and physical activity with alterations in cognitive function after bariatric surgery among patients with severe obesity.

The Preventive Effect of Exercise and Oral Branched-Chain Amino Acid Supplementation on Obesity-Induced Brain Changes in Ldlr-/-.Leiden Mice.

Exercise and dietary interventions are promising approaches to tackle obesity and its obesogenic effects on the brain. We investigated the impact of exercise and possible synergistic effects of exercise and branched-chain amino acids (BCAA) supplementation on the brain and behavior in high-fat-diet (HFD)-induced obese Ldlr-/-.Leiden mice.

Association between hypertension and neurovascular inflammation in both normal-appearing white matter and white matter hyperintensities.

The major vascular cause of dementia is cerebral small vessel disease (SVD), including white matter hyperintensities (WMH) amongst others. While the underlying pathology of SVD remains unclear, chronic hypertension and neuroinflammation are recognized as important risk factors for SVD and for the conversion of normal-appearing white matter (NAWM) to WMH. Unfortunately, most studies investigating the role of neuroinflammation in WMH relied on peripheral blood markers, e.

Impact of White Adipose Tissue on Brain Structure, Perfusion, and Cognitive Function in Patients With Severe Obesity: The BARICO Study.

Background And Objective: While underlying pathophysiology linking obesity to brain health is not completely understood, white adipose tissue (WAT) is considered a key player. In obesity, WAT becomes dysregulated, showing hyperplasia, hypertrophy, and eventually inflammation. This disbalance leads to dysregulated secretion of adipokines influencing both (cardio)vascular and brain health.

The pale spear-nosed bat: A neuromolecular and transgenic model for vocal learning.

Vocal learning, the ability to produce modified vocalizations via learning from acoustic signals, is a key trait in the evolution of speech. While extensively studied in songbirds, mammalian models for vocal learning are rare. Bats present a promising study system given their gregarious natures, small size, and the ability of some species to be maintained in captive colonies.

Short-Term Colony-Stimulating Factor 1 Receptor Inhibition-Induced Repopulation After Stroke Assessed by Longitudinal F-DPA-714 PET Imaging.

Studies on colony-stimulating factor 1 receptor (CSF-1R) inhibition-induced microglia depletion indicated that inhibitor withdrawal allowed the renewal of the microglia compartment via repopulation and resolved the inflammatory imbalance. Therefore, we investigated for the first time (to our knowledge) the effects of microglia repopulation on inflammation and functional outcomes in an ischemic mouse model using translocator protein (TSPO)-PET/CT and MR imaging, ex vivo characterization, and behavioral tests. Eight C57BL/6 mice per group underwent a 30-min transient occlusion of the middle cerebral artery.

Milk fat globule membrane attenuates high fat diet-induced neuropathological changes in obese Ldlr-/-.Leiden mice.

Background: Milk-fat globule membrane (MFGM) is a complex structure secreted by the mammary gland and present in mammalian milk. MFGM contains lipids and glycoproteins as well as gangliosides, which may be involved in myelination processes. Notably, myelination and thereby white matter integrity are often altered in obesity.

The continued need for animals to advance brain research.

Policymakers aim to move toward animal-free alternatives for scientific research and have introduced very strict regulations for animal research. We argue that, for neuroscience research, until viable and translational alternatives become available and the value of these alternatives has been proven, the use of animals should not be compromised.

The Impact of Voluntary Exercise on Stroke Recovery.

Stroke treatment is limited to time-critical thrombectomy and rehabilitation by physiotherapy. Studies report beneficial effects of exercise; however, a knowledge gap exists regarding underlying mechanisms that benefit recovery of brain networks and cognition. This study aims to unravel therapeutic effects of voluntary exercise in stroke-induced mice to develop better personalized treatments.

A Longitudinal PET/MRI Study of Colony-Stimulating Factor 1 Receptor-Mediated Microglia Depletion in Experimental Stroke.

Microglia-induced neuroinflammation after stroke contributes to the exacerbation of postischemic damage but also supports neurorestorative events. Longitudinal molecular imaging of microglia-targeted therapies will support the assessment of target engagement, therapy efficacy, and deciphering of the mode of action. We investigated the effects of chronic colony-stimulating factor 1 receptor (CSF-1R) inhibitor-mediated microglia depletion on translocator protein (TSPO)-dependent neuroinflammation and cerebrovascular parameters using PET/MRI.

Impact of hydroxytyrosol on stroke: tracking therapy response on neuroinflammation and cerebrovascular parameters using PET-MR imaging and on functional outcomes.

Immune cells have been implicated in influencing stroke outcomes depending on their temporal dynamics, number, and spatial distribution after ischemia. Depending on their activation status, immune cells can have detrimental and beneficial properties on tissue outcome after stroke, highlighting the need to modulate inflammation towards beneficial and restorative immune responses. Novel dietary therapies may promote modulation of pro- and anti-inflammatory immune cell functions.

How the COVID-19 pandemic highlights the necessity of animal research.

Recently, a petition was offered to the European Commission calling for an immediate ban on animal testing. Although a Europe-wide moratorium on the use of animals in science is not yet possible, there has been a push by the non-scientific community and politicians for a rapid transition to animal-free innovations. Although there are benefits for both animal welfare and researchers, advances on alternative methods have not progressed enough to be able to replace animal research in the foreseeable future.

Automated Analysis of Stroke Mouse Trajectory Data With Traja.

Quantitative characterization of mouse activity, locomotion and walking patterns requires the monitoring of position and activity over long periods of time. Manual behavioral phenotyping, however, is time and skill-intensive, vulnerable to researcher bias and often stressful for the animals. We present examples for using a platform-independent open source trajectory analysis software, Traja, for semi-automated analysis of high throughput mouse home-cage data for neurobehavioral research.

Impaired mitochondrial complex I function as a candidate driver in the biological stress response and a concomitant stress-induced brain metabolic reprogramming in male mice.

Mitochondria play a critical role in bioenergetics, enabling stress adaptation, and therefore, are central in biological stress responses and stress-related complex psychopathologies. To investigate the effect of mitochondrial dysfunction on the stress response and the impact on various biological domains linked to the pathobiology of depression, a novel mouse model was created. These mice harbor a gene trap in the first intron of the Ndufs4 gene (Ndufs4 mice), encoding the NDUFS4 protein, a structural component of complex I (CI), the first enzyme of the mitochondrial electron transport chain.

Propionic acid and not caproic acid, attenuates nonalcoholic steatohepatitis and improves (cerebro) vascular functions in obese Ldlr .Leiden mice.

The obesity epidemic increases the interest to elucidate impact of short-chain fatty acids on metabolism, obesity, and the brain. We investigated the effects of propionic acid (PA) and caproic acid (CA) on metabolic risk factors, liver and adipose tissue pathology, brain function, structure (by MRI), and gene expression, during obesity development in Ldlr .Leiden mice.

Gut microbiota from persons with attention-deficit/hyperactivity disorder affects the brain in mice.

Background: The impact of the gut microbiota on host physiology and behavior has been relatively well established. Whether changes in microbial composition affect brain structure and function is largely elusive, however. This is important as altered brain structure and function have been implicated in various neurodevelopmental disorders, like attention-deficit/hyperactivity disorder (ADHD).

Vascular reserve in brain resilience: pipes or perfusion?

This scientific commentary refers to ‘Hippocampal vascular reserve associated with cognitive performance and hippocampal volume’, by Perosa (doi: 10.1093/brain/awz383).