Probiotic treatment induces sex-dependent neuroprotection and gut microbiome shifts after traumatic brain injury.

Background: Recent studies have highlighted the potential influence of gut dysbiosis on traumatic brain injury (TBI) outcomes. Alterations in the abundance and diversity of Lactobacillus species may affect immune dysregulation, neuroinflammatory responses, anxiety- and depressive-like behaviors, and neuroprotective mechanisms activated in response to TBI.

Objective: This study aims to evaluate the protective and preventive effects of Pan-probiotic (PP) treatment on the inflammatory response during both the acute and chronic phases of TBI.

The bioenergetics of traumatic brain injury and its long-term impact for brain plasticity and function.

Mitochondria provide the energy to keep cells alive and functioning and they have the capacity to influence highly complex molecular events. Mitochondria are essential to maintain cellular energy homeostasis that determines the course of neurological disorders, including traumatic brain injury (TBI). Various aspects of mitochondria metabolism such as autophagy can have long-term consequences for brain function and plasticity.

Probiotic therapy modulates the brain-gut-liver microbiota axis in a mouse model of traumatic brain injury.

The interplay between gut microbiota and host health is crucial for maintaining the overall health of the body and brain, and it is even more crucial how changes in the bacterial profile can influence the aftermath of traumatic brain injury (TBI). We studied the effects of probiotic treatment after TBI to identify potential changes in hepatic lipid species relevant to brain function. Bioinformatic analysis of the gut microbiota indicated a significant increase in the Firmicutes/Bacteroidetes ratio in the probiotic-treated TBI group compared to sham and untreated TBI groups.

Thyroid hormone T4 mitigates traumatic brain injury in mice by dynamically remodeling cell type specific genes, pathways, and networks in hippocampus and frontal cortex.

The complex pathology of mild traumatic brain injury (mTBI) is a main contributor to the difficulties in achieving a successful therapeutic regimen. Thyroxine (T4) administration has been shown to prevent the cognitive impairments induced by mTBI in mice but the mechanism is poorly understood. To understand the underlying mechanism, we carried out a single cell transcriptomic study to investigate the spatiotemporal effects of T4 on individual cell types in the hippocampus and frontal cortex at three post-injury stages in a mouse model of mTBI.

Exercise epigenetics is fueled by cell bioenergetics: Supporting role on brain plasticity and cognition.

Exercise has the unique aptitude to benefit overall health of body and brain. Evidence indicates that the effects of exercise can be saved in the epigenome for considerable time to elevate the threshold for various diseases. The action of exercise on epigenetic regulation seems central to building an "epigenetic memory" to influence long-term brain function and behavior.

Probiotic treatment causes sex-specific neuroprotection after traumatic brain injury in mice.

Background: Recent studies have shed light on the potential role of gut dysbiosis in shaping traumatic brain injury (TBI) outcomes. Changes in the levels and types of bacteria present might impact the immune system disturbances, neuroinflammatory responses, anxiety and depressive-like behaviors, and compromised neuroprotection mechanisms triggered by TBI.

Objective: This study aimed to investigate the effects of a daily pan-probiotic (PP) mixture in drinking water containing strains of and administered for either two or seven weeks before inducing TBI on both male and female mice.

Altering the Trajectory of Perfusion-Diffusion Deficits Using A BDNF Mimetic Acutely After TBI is Associated with Improved Functional Connectivity.

Traumatic brain injury (TBI) results in metabolic deficits and functionally compromised tissue. The BDNF mimetic R13 has a significant positive effect on both tissue metabolism and behavioral outcome after TBI, indicating a promising therapeutic. To understand the mechanism of action for this intervention, we determined whether there was any association between the underlying metabolic insult and any improvement in resting state functional connectivity (FC) with MRI, or whether R13 acts through mechanisms unrelated to metabolic recovery.

Humanin ameliorates TBI-related cognitive impairment by attenuating mitochondrial dysfunction and inflammation.

Traumatic brain injury (TBI) often results in a reduction of the capacity of cells to sustain energy demands, thus, compromising neuronal function and plasticity. Here we show that the mitochondrial activator humanin (HN) counteracts a TBI-related reduction in mitochondrial bioenergetics, including oxygen consumption rate. HN normalized the disruptive action of TBI on memory function, and restored levels of synaptic proteins (synapsin 1 and p-CREB).

The BDNF mimetic R-13 attenuates TBI pathogenesis using TrkB-related pathways and bioenergetics.

Traumatic brain injury (TBI) is major neurological burden globally, and effective treatments are urgently needed. TBI is characterized by a reduction in energy metabolism and synaptic function that seems a primary cause of neuronal dysfunction. R13, a small drug and BDNF mimetic showed promising results in improving spatial memory and anxiety-like behavior after TBI.

Liver acts as a metabolic gate for the traumatic brain injury pathology: Protective action of thyroid hormone.

Clinical evidence indicates that injury to the brain elicits systemic metabolic disturbances that contributes to the brain pathology. Since dietary fructose is metabolized in the liver, we explored mechanisms by which traumatic brain injury (TBI) and dietary fructose influence liver function and their possible repercussions to brain. Consumption of fructose contributed to the detrimental effects of TBI on liver operation, in terms of glucose and lipid metabolism, de novo lipogenesis, lipid peroxidation.

Traumatic brain injury alters the gut-derived serotonergic system and associated peripheral organs.

Most efforts to understand the pathology of traumatic brain injury (TBI) have been centered on the brain, ignoring the role played by systemic physiology. Gut-derived serotonin is emerging as a major regulator of systemic homeostasis involving various organs and tissues throughout the body. Here, we shed light on the roles occupied by gut-derived serotonin and its downstream metabolic targets in the systemic pathogenesis of TBI.

Joint cell segmentation and cell type annotation for spatial transcriptomics.

RNA hybridization-based spatial transcriptomics provides unparalleled detection sensitivity. However, inaccuracies in segmentation of image volumes into cells cause misassignment of mRNAs which is a major source of errors. Here, we develop JSTA, a computational framework for joint cell segmentation and cell type annotation that utilizes prior knowledge of cell type-specific gene expression.

Mild traumatic brain injury induces microvascular injury and accelerates Alzheimer-like pathogenesis in mice.

Introduction: Traumatic brain injury (TBI) is considered as the most robust environmental risk factor for Alzheimer's disease (AD). Besides direct neuronal injury and neuroinflammation, vascular impairment is also a hallmark event of the pathological cascade after TBI. However, the vascular connection between TBI and subsequent AD pathogenesis remains underexplored.

Dietary fructose as a model to explore the influence of peripheral metabolism on brain function and plasticity.

High consumption of fructose has paralleled an explosion in metabolic disorders including obesity and type 2 diabetes. Even more problematic, sustained consumption of fructose is perceived as a threat for brain function and development of neurological disorders. The action of fructose on peripheral organs is an excellent model to understand how systemic physiology impacts the brain.

The interaction between brain and liver regulates lipid metabolism in the TBI pathology.

To shed light on the impact of systemic physiology on the pathology of traumatic brain injury (TBI), we examine the effects of TBI (concussive injury) and dietary fructose on critical aspects of lipid homeostasis in the brain and liver of young-adult rats. Lipids are integral components of brain structure and function, and the liver has a role on the synthesis and metabolism of lipids. Fructose is mainly metabolized in the liver with potential implications for brain function.

Diet and depression: exploring the biological mechanisms of action.

The field of nutritional psychiatry has generated observational and efficacy data supporting a role for healthy dietary patterns in depression onset and symptom management. To guide future clinical trials and targeted dietary therapies, this review provides an overview of what is currently known regarding underlying mechanisms of action by which diet may influence mental and brain health. The mechanisms of action associating diet with health outcomes are complex, multifaceted, interacting, and not restricted to any one biological pathway.

Multi-Tissue Multi-Omics Nutrigenomics Indicates Context-Specific Effects of Docosahexaenoic Acid on Rat Brain.

Scope: The influence of docosahexaenoic acid (DHA) on cardiometabolic and cognitive phenotypes, and multi-omic alterations in the brain under two metabolic conditions is explored to understand context-specific nutritional effects.

Methods And Results: Rats are randomly assigned to a DHA-rich or a control chow diet while drinking water or high fructose solution, followed by profiling of metabolic and cognitive phenotypes and the transcriptome and DNA methylome of the hypothalamus and hippocampus. DHA reduces serum triglyceride and improves insulin resistance and memory exclusively in the fructose-consuming rats.

Cerebral Fructose Metabolism as a Potential Mechanism Driving Alzheimer's Disease.

The loss of cognitive function in Alzheimer's disease is pathologically linked with neurofibrillary tangles, amyloid deposition, and loss of neuronal communication. Cerebral insulin resistance and mitochondrial dysfunction have emerged as important contributors to pathogenesis supporting our hypothesis that cerebral fructose metabolism is a key initiating pathway for Alzheimer's disease. Fructose is unique among nutrients because it activates a survival pathway to protect animals from starvation by lowering energy in cells in association with adenosine monophosphate degradation to uric acid.

Host Genetic Background and Gut Microbiota Contribute to Differential Metabolic Responses to Fructose Consumption in Mice.

Background: It is unclear how high fructose consumption induces disparate metabolic responses in genetically diverse mouse strains.

Objective: We aimed to investigate whether the gut microbiota contributes to differential metabolic responses to fructose.

Methods: Eight-week-old male C57BL/6J (B6), DBA/2J (DBA), and FVB/NJ (FVB) mice were given 8% fructose solution or regular water (control) for 12 wk.