Oxidative stress alters mitochondrial homeostasis in isolated brain capillaries.

Background: Neurovascular deficits and blood-brain barrier (BBB) dysfunction are major hallmarks of brain trauma and neurodegenerative diseases. Oxidative stress is a prominent contributor to neurovascular unit (NVU) dysfunction and can propagate BBB disruption. Oxidative damage results in an imbalance of mitochondrial homeostasis, which can further drive functional impairment of brain capillaries.

Longitudinal changes in neural responses to fearful faces in adolescents with anorexia nervosa - A fMRI study.

Objective: Although proven neuronal changes are correlated with anorexia nervosa (AN), where these changes occur and how they change during the course of this disease are often unclear; this is especially true regarding emotion processing, e.g., of anxiety, despite a growing body of literature on its importance for the pathophysiology and clinical course of patients with AN.

Dendritic/antigen presenting cell mediated provision of T-cell receptor gamma delta (TCRγδ) expressing cells contributes to improving antileukemic reactions ex vivo.

T-cell receptor gamma delta (TCRγδ) expressing T-cells are known to mediate an MHC-independent immune response and could therefore qualify for immune therapies. We examined the influence of dendritic cells(DC)/antigen presenting cell (APC) generated from blast-containing whole blood (WB) samples from AML and MDS patients on the provision of (leukemia-specific) TCRγδ expressing T-cells after mixed lymphocyte culture (MLC). Kit-M (granulocyte-macrophage colony-stimulating factor (GM-CSF) + prostaglandin E1 (PGE1)) or Kit-I (GM-CSF + Picibanil) were used to generate leukemia derived APC/DC (DC)from WB, which were subsequently used to stimulate T-cell enriched MLC.

Glioblastoma Standard of Care: Effects on Tumor Evolution and Reverse Translation in Preclinical Models.

Glioblastoma (GBM) presents a significant public health challenge as the deadliest and most common malignant brain tumor in adults. Despite standard-of-care treatment, which includes surgery, radiation, and chemotherapy, mortality rates are high, underscoring the critical need for advancing GBM therapy. Over the past two decades, numerous clinical trials have been performed, yet only a small fraction demonstrated a benefit, raising concerns about the predictability of current preclinical models.

Optimization, Characterization, and Comparison of Two Luciferase-Expressing Mouse Glioblastoma Models.

Glioblastoma (GBM) is the most aggressive brain cancer. To model GBM in research, orthotopic brain tumor models, including syngeneic models like GL261 and genetically engineered mouse models like TRP, are used. In longitudinal studies, tumor growth and the treatment response are typically tracked with in vivo imaging, including bioluminescence imaging (BLI), which is quick, cost-effective, and easily quantifiable.

Impaired recognition of interactive intentions in adults with autism spectrum disorder not attributable to differences in visual attention or coordination via eye contact and joint attention.

Altered nonverbal communication patterns especially with regard to gaze interactions are commonly reported for persons with autism spectrum disorder (ASD). In this study we investigate and differentiate for the first time the interplay of attention allocation, the establishment of shared focus (eye contact and joint attention) and the recognition of intentions in gaze interactions in adults with ASD compared to control persons. Participants interacted via gaze with a virtual character (VC), who they believed was controlled by another person.

Cognitive decline, Aβ pathology, and blood-brain barrier function in aged 5xFAD mice.

Background: Patients with Alzheimer's disease (AD) develop blood-brain barrier dysfunction to varying degrees. How aging impacts Aβ pathology, blood-brain barrier function, and cognitive decline in AD remains largely unknown. In this study, we used 5xFAD mice to investigate changes in Aβ levels, barrier function, and cognitive decline over time.

Granulocyte-Macrophage-Colony-Stimulating-Factor Combined with Prostaglandin E1 Create Dendritic Cells of Leukemic Origin from AML Patients' Whole Blood and Whole Bone Marrow That Mediate Antileukemic Processes after Mixed Lymphocyte Culture.

Although several (chemotherapeutic) protocols to treat acute myeloid leukemia (AML) are available, high rates of relapses in successfully treated patients occur. Strategies to stabilize remissions are greatly needed. The combination of the (clinically approved) immune-modulatory compounds Granulocyte-Macrophage-Colony-Stimulating-Factor (GM-CSF) and Prostaglandine E1 (PGE-1) (Kit-M) converts myeloid blasts into dendritic cells of leukemic origin (DC).

A high-throughput single-cell RNA expression profiling method identifies human pericyte markers.

Aims: We sought to identify and optimise a universally available histological marker for pericytes in the human brain. Such a marker could be a useful tool for researchers. Further, identifying a gene expressed relatively specifically in human pericytes could provide new insights into the biological functions of this fascinating cell type.

Proteasome inhibition protects blood-brain barrier P-glycoprotein and lowers Aβ brain levels in an Alzheimer's disease model.

Background: Loss of P-glycoprotein (P-gp) at the blood-brain barrier contributes to amyloid-β (Aβ) brain accumulation in Alzheimer's disease (AD). Using transgenic human amyloid precursor protein (hAPP)-overexpressing mice (Tg2576), we previously showed that Aβ triggers P-gp loss by activating the ubiquitin-proteasome pathway, which leads to P-gp degradation. Furthermore, we showed that inhibiting the ubiquitin-activating enzyme (E1) prevents P-gp loss and lowers Aβ accumulation in the brain of hAPP mice.

Increased Expression of Anaphylatoxin C5a-Receptor-1 in Neutrophils and Natural Killer Cells of Preterm Infants.

Preterm infants are susceptible to infection and their defense against pathogens relies largely on innate immunity. The role of the complement system for the immunological vulnerability of preterm infants is less understood. Anaphylatoxin C5a and its receptors C5aR1 and -2 are known to be involved in sepsis pathogenesis, with C5aR1 mainly exerting pro-inflammatory effects.

ABCB1 and ABCG2 Regulation at the Blood-Brain Barrier: Potential New Targets to Improve Brain Drug Delivery.

The drug efflux transporters ABCB1 and ABCG2 at the blood-brain barrier limit the delivery of drugs into the brain. Strategies to overcome ABCB1/ABCG2 have been largely unsuccessful, which poses a tremendous clinical problem to successfully treat central nervous system (CNS) diseases. Understanding basic transporter biology, including intracellular regulation mechanisms that control these transporters, is critical to solving this clinical problem.

The potential role of serum extracellular vesicle derived small RNAs in AML research as non-invasive biomarker.

Background: Extracellular vesicles (EV) are cell-derived vesicles released by all cells in health and disease. Accordingly, EVs are also released by cells in acute myeloid leukemia (AML), a hematologic malignancy characterized by uncontrolled growth of immature myeloid cells, and these EVs likely carry markers and molecular cargo reflecting the malignant transformation occurring in diseased cells. Monitoring antileukemic or proleukemic processes during disease development and treatment is essential.

Neural mechanisms underlying social recognition and theory of mind in adolescent patients with bulimia nervosa and transdiagnostic comparison with anorexia nervosa.

Introduction: Theory of mind (ToM) is important for social interactions and typical development and has been found to be impaired in patients with anorexia nervosa (AN) and bulimia nervosa (BN). Hypoactivation in frontotemporal brain regions seems to be the underlying neural mechanism in AN while whole-brain analyses in BN are lacking.

Methods: We used the well-validated social recognition task fMRI paradigm to assess ToM in a total of 72 female adolescents (16 BN, 18 AN and 38 matched healthy controls [HC]).

Description and optimization of a multiplex bead-based flow cytometry method (MBFCM) to characterize extracellular vesicles in serum samples from patients with hematological malignancies.

Extracellular Vesicles (EVs) are membranous vesicles produced by all cells under physiological and pathological conditions. In hematological malignancies, tumor-derived EVs might reprogram the bone marrow environment, suppress antileukemic immunity, mediate drug resistance and interfere with immunotherapies. EVs collected from the serum of leukemic samples might correlate with disease stage, drug-/immunological resistance, or might correlate with antileukemic immunity/immune response.

Brain barriers virtual: an interim solution or future opportunity?

Background: Scientific conferences are vital communication events for scientists in academia, industry, and government agencies. In the brain barriers research field, several international conferences exist that allow researchers to present data, share knowledge, and discuss novel ideas and concepts. These meetings are critical platforms for researchers to connect and exchange breakthrough findings on a regular basis.

Blood-brain barrier leakage in Alzheimer's disease: From discovery to clinical relevance.

Alzheimer's disease (AD) is the most common form of dementia. AD brain pathology starts decades before the onset of clinical symptoms. One early pathological hallmark is blood-brain barrier dysfunction characterized by barrier leakage and associated with cognitive decline.

Hyperoxia/Hypoxia Exposure Primes a Sustained Pro-Inflammatory Profile of Preterm Infant Macrophages Upon LPS Stimulation.

Preterm infants are highly susceptible to sustained lung inflammation, which may be triggered by exposure to multiple environmental cues such as supplemental oxygen (O) and infections. We hypothesized that dysregulated macrophage (MФ) activation is a key feature leading to inflammation-mediated development of bronchopulmonary dysplasia (BPD) in preterm infants. Therefore, we aimed to determine age-dependent differences in immune responses of monocyte-derived MФ comparing cord blood samples derived from preterm (n=14) and term (n=19) infants as well as peripheral blood samples from healthy adults (n=17) after lipopolysaccharide (LPS) exposure.

Differentiating brain function of punishment versus reward processing in conduct disorder with and without attention deficit hyperactivity disorder.

Objectives: Conduct disorder (CD) and attention-deficit/hyperactivity disorder (ADHD) are reported to co-occur in about 30-50% of affected individuals. Research suggests that poor reinforcement-based decision-making may contribute to impaired social functioning in both youths with CD and ADHD. Considering its frequent co-occurrence this raises the question whether decision-making deficits in both disorders have a disorder-specific and/or shared neurobiological basis.

Temporal Behavioral Parameters of On-Going Gaze Encounters in a Virtual Environment.

To navigate the social world, humans heavily rely on gaze for non-verbal communication as it conveys information in a highly dynamic and complex, yet concise manner: For instance, humans utilize gaze effortlessly to direct and infer the attention of a possible interaction partner. Many traditional paradigms in social gaze research though rely on static ways of assessing gaze interaction, e.g.

Protecting P-glycoprotein at the blood-brain barrier from degradation in an Alzheimer's disease mouse model.

Background: Failure to clear Aβ from the brain is partly responsible for Aβ brain accumulation in Alzheimer's disease (AD). A critical protein for clearing Aβ across the blood-brain barrier is the efflux transporter P-glycoprotein (P-gp). In AD, P-gp levels are reduced, which contributes to impaired Aβ brain clearance.

The Blood-Brain Barrier in Alzheimer's Disease.

The accumulation of neurotoxic amyloid-beta (Aβ) in the brain is one of the characteristic hallmarks of Alzheimer's disease (AD). Aβ-peptide brain homeostasis is governed by its production and various clearance mechanisms. The blood-brain barrier provides a large surface area for influx and efflux mechanisms into and out of the brain.