Evaluation of the Safety and Impact of Heat-Treated KM2 Fermentation on Gut Microbiome Architecture.

Postbiotics, bioactive compounds from the fermentation process by probiotics, are gaining attention for their potential health benefits as safer alternatives to live probiotic microbes. is a well-studied probiotic species known for promoting gut health and immune modulation. However, the safety and effects of its postbiotic formulations on the gut microbiome structure remain less explored.

Exploring the Characteristics of Gut Microbiota Associated with Depression via the Depression Assessment Scales.

Depression is a prevalent mental disorder with an increasing economic burden, and its pathogenesis remains poorly understood. Given the emerging evidence linking the gut microbiota to mental health, a better understanding of microbial profiles associated with depression is necessary. Here, we explore the association between gut microbiota and depression by utilizing 16S rRNA amplicon sequencing and depression assessment scales, including the Hamilton Depression Rating Scale (HDRS) and the Beck Depression Inventory (BDI).

Stress hyperglycemia exacerbates inflammatory brain injury after stroke.

Post-stroke hyperglycemia occurs in 30% - 60% of ischemic stroke patients as part of the systemic stress response, but neither clinical evidence nor pre-clinical studies indicate whether post-stroke hyperglycemia affects stroke outcome. Here we investigated this issue using a mouse model of permanent ischemia. Mice were maintained either normoglycemic or hyperglycemic during the interval of 17 - 48 hours after ischemia onset.

Neuronal Oxidative Stress Promotes α-Synuclein Aggregation In Vivo.

Both genetic and environmental factors increase risk for Parkinson's disease. Many of the known genetic factors influence α-synuclein aggregation or degradation, whereas most of the identified environmental factors produce oxidative stress. Studies using in vitro approaches have identified mechanisms by which oxidative stress can accelerate the formation of α-synuclein aggregates, but there is a paucity of evidence supporting the importance of these processes over extended time periods in brain.

Recovery of consolidation after sleep following stroke-interaction of slow waves, spindles, and GABA.

Sleep is known to promote recovery after stroke. Yet it remains unclear how stroke affects neural processing during sleep. Using an experimental stroke model in rats along with electrophysiological monitoring of neural firing and sleep microarchitecture, here we show that sleep processing is altered by stroke.

Blast-induced axonal degeneration in the rat cerebellum in the absence of head movement.

Blast exposure can injure brain by multiple mechanisms, and injury attributable to direct effects of the blast wave itself have been difficult to distinguish from that caused by rapid head displacement and other secondary processes. To resolve this issue, we used a rat model of blast exposure in which head movement was either strictly prevented or permitted in the lateral plane. Blast was found to produce axonal injury even with strict prevention of head movement.

Coordinated increase of reliable cortical and striatal ensemble activations during recovery after stroke.

Skilled movements rely on a coordinated cortical and subcortical network, but how this network supports motor recovery after stroke is unknown. Previous studies focused on the perilesional cortex (PLC), but precisely how connected subcortical areas reorganize and coordinate with PLC is unclear. The dorsolateral striatum (DLS) is of interest because it receives monosynaptic inputs from motor cortex and is important for learning and generation of fast reliable actions.

α-synuclein aggregates induce c-Abl activation and dopaminergic neuronal loss by a feed-forward redox stress mechanism.

Oxidative stress and α-synuclein aggregation both drive neurodegeneration in Parkinson's disease, and the protein kinase c-Abl provides a potential amplifying link between these pathogenic factors. Suppressing interactions between these factors may thus be a viable therapeutic approach for this disorder. To evaluate this possibility, pre-formed α-synuclein fibrils (PFFs) were used to induce α-synuclein aggregation in neuronal cultures.

Hip and Subtrochanteric or Femoral Shaft Fractures after Bisphosphonate Use in Korean Women, Using Korean National Sample Cohort.

Background: Concern about bisphosphonate-associated subtrochanteric and femoral shaft (ST/FS) fractures has been raised. However, its real risk is still debatable, because there is no study to estimate risk and benefit of bisphosphonate. The objective of this study was to evaluate the risk of typical hip fractures and ST/FS fractures among bisphosphonate users using nationwide database.

Cofilin-actin rod formation in experimental stroke is attenuated by therapeutic hypothermia and overexpression of the inducible 70 kD inducible heat shock protein (Hsp70).

Background And Purpose: Cofilin-actin rods are covalently linked aggregates of cofilin-1 and actin. Under ischemic conditions, these rods have been observed in neuronal dendrites and axons and may contribute to the loss of these processes. Hypothermia (Hypo) and the 70 kD inducible heat shock protein (Hsp70) are both known to improve outcomes after stroke, but the mechanisms are uncertain.

Anterior Cortical Window Technique Instead of Extended Trochanteric Osteotomy in Revision Total Hip Arthroplasty: A Minimum 10-Year Follow-up.

Background: The anterior cortical window technique was developed to facilitate stem removal in revision total hip arthroplasty (THA). In this technique, only the anterior cortex of the proximal femur is osteomized; the trochanter, lateral cortex, and medial cortex remain intact. Therefore, a new stem can be press-fitted into the femur and mediolateral stability can be obtained.

Emergent modular neural control drives coordinated motor actions.

A remarkable feature of motor control is the ability to coordinate movements across distinct body parts into a consistent, skilled action. To reach and grasp an object, 'gross' arm and 'fine' dexterous movements must be coordinated as a single action. How the nervous system achieves this coordination is currently unknown.

Cofilin-actin rod formation in neuronal processes after brain ischemia.

Functional impairment after brain ischemia results in part from loss of neuronal spines and dendrites, independent of neuronal death. Cofilin-actin rods are covalently linked aggregates of cofilin-1 and actin that form in neuronal processes (neurites) under conditions of ATP depletion and oxidative stress, and which cause neurite degeneration if not disassembled. ATP depletion and oxidative stress occur with differing severity, duration, and time course in different ischemic conditions.

EAAC1 gene deletion reduces adult hippocampal neurogenesis after transient cerebral ischemia.

Several studies have demonstrated that excitatory amino acid carrier-1 (EAAC1) gene deletion exacerbates hippocampal and cortical neuronal death after ischemia. However, presently there are no studies investigating the role of EAAC1 in hippocampal neurogenesis. In this study, we tested the hypothesis that reduced cysteine transport into neurons by EAAC1 knockout negatively affects adult hippocampal neurogenesis under physiological or pathological states.

Effects of Veliparib on Microglial Activation and Functional Outcomes after Traumatic Brain Injury in the Rat and Pig.

The inflammation response induced by brain trauma can impair recovery. This response requires several hours to develop fully and thus provides a clinically relevant therapeutic window of opportunity. Poly(ADP-ribose) polymerase inhibitors suppress inflammatory responses, including brain microglial activation.

Bioenergetic state regulates innate inflammatory responses through the transcriptional co-repressor CtBP.

The innate inflammatory response contributes to secondary injury in brain trauma and other disorders. Metabolic factors such as caloric restriction, ketogenic diet, and hyperglycemia influence the inflammatory response, but how this occurs is unclear. Here, we show that glucose metabolism regulates pro-inflammatory NF-κB transcriptional activity through effects on the cytosolic NADH:NAD ratio and the NAD(H) sensitive transcriptional co-repressor CtBP.

A data-driven approach for evaluating multi-modal therapy in traumatic brain injury.

Combination therapies targeting multiple recovery mechanisms have the potential for additive or synergistic effects, but experimental design and analyses of multimodal therapeutic trials are challenging. To address this problem, we developed a data-driven approach to integrate and analyze raw source data from separate pre-clinical studies and evaluated interactions between four treatments following traumatic brain injury. Histologic and behavioral outcomes were measured in 202 rats treated with combinations of an anti-inflammatory agent (minocycline), a neurotrophic agent (LM11A-31), and physical therapy consisting of assisted exercise with or without botulinum toxin-induced limb constraint.

Microglial activation induced by the alarmin S100B is regulated by poly(ADP-ribose) polymerase-1.

Brain injury resulting from stroke or trauma can be exacerbated by the release of proinflammatory cytokines, proteases, and reactive oxygen species by activated microglia. The microglial activation resulting from brain injury is mediated in part by alarmins, which are signaling molecules released from damaged cells. The nuclear enzyme poly(ADP-ribose) polymerase-1 (PARP-1) has been shown to regulate microglial activation after brain injury, and here we show that signaling effects of the alarmin S100B are regulated by PARP-1.

Neuronal Glutathione Content and Antioxidant Capacity can be Normalized In Situ by N-acetyl Cysteine Concentrations Attained in Human Cerebrospinal Fluid.

N-acetyl cysteine (NAC) supports the synthesis of glutathione (GSH), an essential substrate for fast, enzymatically catalyzed oxidant scavenging and protein repair processes. NAC is entering clinical trials for adrenoleukodystrophy, Parkinson's disease, schizophrenia, and other disorders in which oxidative stress may contribute to disease progression. However, these trials are hampered by uncertainty about the dose of NAC required to achieve biological effects in human brain.

Targeted Lipid Profiling Discovers Plasma Biomarkers of Acute Brain Injury.

Prior efforts to identify a blood biomarker of brain injury have relied almost exclusively on proteins; however their low levels at early time points and poor correlation with injury severity have been limiting. Lipids, on the other hand, are the most abundant molecules in the brain and readily cross the blood-brain barrier. We previously showed that certain sphingolipid (SL) species are highly specific to the brain.

Melatonin Reduces Hypoglycemia-Induced Neuronal Death in Rats.

Melatonin, N-aceyl-5-methoxytryptamine, is the main secretory product of the pineal gland and has neuroprotective effects on several brain injuries, including ischemic stroke. In the present study, we hypothesized that exogenous melatonin may decrease hypoglycemia-induced neuronal death through the prevention of superoxide generation. To test our hypothesis, hypoglycemia was induced by injecting human insulin (10 U/kg, i.

Robust neuroprosthetic control from the stroke perilesional cortex.

Intracortical brain-machine interfaces (BMIs) may eventually restore function in those with motor disability after stroke. However, current research into the development of intracortical BMIs has focused on subjects with largely intact cortical structures, such as those with spinal cord injury. Although the stroke perilesional cortex (PLC) has been hypothesized as a potential site for a BMI, it remains unclear whether the injured motor cortical network can support neuroprosthetic control directly.

Assessment at the single-cell level identifies neuronal glutathione depletion as both a cause and effect of ischemia-reperfusion oxidative stress.

Oxidative stress contributes to neuronal death in brain ischemia-reperfusion. Tissue levels of the endogenous antioxidant glutathione (GSH) are depleted during ischemia-reperfusion, but it is unknown whether this depletion is a cause or an effect of oxidative stress, and whether it occurs in neurons or other cell types. We used immunohistochemical methods to evaluate glutathione, superoxide, and oxidative stress in mouse hippocampal neurons after transient forebrain ischemia.

An automated behavioral box to assess forelimb function in rats.

Background: Rodent forelimb reaching behaviors are commonly assessed using a single-pellet reach-to-grasp task. While the task is widely recognized as a very sensitive measure of distal limb function, it is also known to be very labor-intensive, both for initial training and the daily assessment of function.

New Method: Using components developed by open-source electronics platforms, we have designed and tested a low-cost automated behavioral box to measure forelimb function in rats.