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Pathologic evaluation of the human suprachiasmatic nucleus in severe dementia.

Sleep disruption and other circadian rhythm disturbances are frequently seen in dementia patients. In this study, we examined the suprachias … using a stereological approach to sample the average total number of positively stained neurons and astrocytes in 10 different 0.1mm2 microscopic fields in the dorsal subdivision of the SCN. Patients with Alzheimer disease exhibited a significant decrease in vasopressin (9.75 vs 16.7, p < 0.001) and neurotensin (6.82 vs 9.63, p < 0.002) neurons, as well as a …

Microvessel density is a prognostic indicator for patients with astroglial brain tumors.

BACKGROUND: Microvessel density in tumors, a measure of angiogenesis, has been shown to be a prognostic indicator that correlates with an increased risk of metastasis in various epithelial cancers and with overall and relapse free survival in patients with breast cancer. Astrocytic brain tumors, particularly malignant astrocytomas, are recognized to be highly vascular tumors with potent angiogenic activity. However, the prognostic significance of microvessel density in these tumors is not known. METHODS: Sections from formalin fixed paraffin embedded tumor tissue from 93 unselected adult pati

Mapping of phenytoin-inducible cytochrome P450 immunoreactivity in the mouse central nervous system.

The distribution of phenytoin-inducible cytochrome P450 in non-treated mouse brain and spinal cord was analysed immunohistochemically using … parison with astroglia, which is characterized by glial fibrillary acidic protein-positiveness, the astrocytes, which are also P450IIB1* reactive, occurred only in subpial and subependymal layers, and in large fiber tracts of the spinal cord and brainstem, where they were attached to the vascular system. Otherwise, the glial fibrillary acidic protein-positiv …

A case of Creutzfeldt-Jakob disease.

The case is reported of a 64-year-old woman with ataxia and dementia progressing to a state of extrapyramidal rigidity and death in 10 months. The neuropathological changes characterised by severe nerve cell degeneration and loss, a hypertrophic astrocytic gliosis and a status spongiosus were widespread in the cerebral cortex, corpus striatum and cerebellum and confirmed the clinical diagnosis of Creutzfeldt-Jakob disease.

Non-invasive brain stimulation and glymphatic function: an aquaporin-4 perspective.

The glymphatic system is a brain-wide fluid transport network in which cerebrospinal fluid enters along periarterial spaces, exchanges with interstitial fluid within the parenchyma, supports the redistribution and clearance of interstitial solutes, and drains toward meningeal and extracranial lymphatic pathways. Aquaporin-4 (AQP4), a water channel highly enriched at perivascular astrocytic endfeet, forms a polarized astroglial membrane interface that facilitates water exchange across the gliovascular compartment and critically shapes glymphatic transport. While non-invasive brain stimulation h

Human Blood-Brain Tumor Barrier on a Chip to Investigate Personalized Treatment for Glioblastoma Patients.

The inherent characteristics of glioblastoma (GBM), including tumoral heterogeneity and invasive capacity, combined with the presence of the … roengineered model that mimics the BBTB within the GBM margin, incorporating a 3D network of normal astrocytes and GBM cells isolated from patients newly diagnosed with GBM. The interaction between GBM cells and stromal cells results in increased vascular permeability, reactive gliosis, alterations in astrocyte behavior and immune responses to foster tumor i …

Targeting glial PD-1/PD-L1 restores microglial homeostasis and reduces neuronal hyperactivity in an Alzheimer's disease model.

Alzheimer's disease (AD) involves complex neuroimmune dysregulation, and the role of immune checkpoint pathways in regulating neuro-glial interactions and intrinsic glial homeostasis remains unclear. In AD, glial expression of programmed cell death protein 1 (PD-1) and its ligand (PD-L1) is elevated in mouse models and human patients, suggesting involvement of immune checkpoint signaling in glial function. To define the role of this pathway in the AD brain, we locally modulated PD-1/PD-L1 signaling by intracortical anti-PD-L1 injection in 8-10-month-old 5xFAD mice, combined with in vivo two-ph

Molecular pathways and diagnosis in spatially resolved Alzheimer's hippocampal atlas.

We employed Stereo-seq combined with single-nucleus RNA sequencing (snRNA-seq) to investigate the gene expression and cell composition chang … nd integration of Stereo-seq map with Aβ staining revealed a sequential enrichment of microglia and astrocytes around Aβ plaques. Finally, reduced brain-derived extracellular vesicles carrying cholecystokinin (CCK) and peripheral myelin protein 2 (PMP2) in AD plasma highlighted their diagnostic potential for clinical applications.

Differential associations of APOE and TREM2 variants with glial fibrillary acidic protein and neurofilament light in plasma of UK Biobank participants support distinct disease mechanisms.

Plasma levels of glial fibrillary acidic protein (GFAP) and neurofilament light (NEFL) are key dementia biomarkers. GFAP and NEFL represent different underlying disease processes, i.e. astrocytic activation vs. neuronal damage. The associations of established genetic risk variants with these biomarkers may reflect time course and mechanisms by which the respective genes influence disease risk. Therefore, we investigated the association of the established high-effect dementia variants in APOE and TREM2 with these biomarkers, in a large population cohort of over 50,000 participants from the UK B

Neuroglia in mood disorders.

Multiple lines of evidence indicate that mood disorders, such as major depressive and bipolar disorder, are associated with abnormalities in neuroglial cells. This chapter discusses the existing literature investigating the potential role of astrocytes, oligodendrocytes, and microglia in mood pathology. We will describe evidence from in vivo imaging, postmortem, animal models based on (stress) paradigms that mimic depressive-like behavior, and biomarker studies in blood and cerebrospinal fluid in patients with mood disorders. The effect of medication used in the treatment of mood disorders, su…

From skin to spinal Cord: How IL-17a Drives psoriatic chronic itch.

Interleukin-17a (IL-17a) has been established as a master regulator of inflammatory cascades in psoriasis pathogenesis. Monoclonal antibodies targeting IL-17a have demonstrated significant efficacy in relieving psoriasis-related symptoms, including the rapid alleviation of chronic itching. However, whether IL-17a is involved in chronic psoriatic pruritus and the specific mechanisms of its action remain poorly understood. In this study, we demonstrate that IL-17a significantly exacerbates chronic itch in a murine model of psoriasis. Mechanistically, IL-17a upregulation in psoriatic skin tissues

Протеин цитруллинирование в амиотропическом боковом склерозе и других нейродегенеративных заболеваниях.

Protein citrullination (PC) — посттранслатальная модификация (PTM), преобразующая пептидил аргинин в пептидил citrulline. Aberrant PC является отличительной чертой нейродегенеративных заболеваний, включая амиотрофный боковой склероз (ALS), болезнь Альцгеймера, болезнь Паркинсона, прионное заболевание и множественный склероз. Среди этих заболеваний наблюдается резкий рост ПК в реактивных астроцитах. Были выявлены некоторые цитуллинированные белки. Наиболее заметными являются астроцитические цитоскелетные белки, такие, как GFAP и виментин, и миелинский белок MBP. Недавнее исследование ALS выявил

Совпадение в аннотации оригинала
Protein citrullination (PC) is a posttranslational modification (PTM) that converts a peptidyl arginine into a peptidyl citrulline. Aberrant … sease, and multiple sclerosis. Common among these diseases is a dramatic increase of PC in reactive astrocytes. Some citrullinated proteins have been identified. The most prominent are astrocytic cytoskeletal proteins such as GFAP and vimentin, and myelin protein MBP. Recent investigation in ALS has revealed new changes, including a decreased PC in neurons a …

Lack of the Ig cell adhesion molecule BT-IgSF (IgSF11) induced behavioral changes in the open maze, water maze and resident intruder test.

The brain- and testis-specific Ig superfamily protein (BT-IgSF, also termed IgSF11) is a homotypic cell adhesion protein. In the nervous system, BT-IgSF regulates the stability of AMPA receptors in the membrane of cultured hippocampal neurons, modulates the connectivity of chandelier cells and controls gap junction-mediated astrocyte-astrocyte communication. Here, we performed behavioral tests in BT-IgSF-deficient mice. BT-IgSF-deficient mice were similar to control littermates with respect to their reflexes, motor coordination and gating, and associative learning. However, BT-IgSF-deficient m

A preliminary transcriptomic analysis of the orbitofrontal cortex of antisocial individuals.

AIMS: Antisocial personality disorder (ASPD) and conduct disorder (CD) are characterized by a persistent pattern of violations of societal n … uggest that ASPD and CD feature a complex array of functional deficits in the pyramidal neurons and astrocytes of the OFC. In turn, these aberrances may contribute to the reduced OFC connectivity observed in antisocial subjects. Future analyses on larger cohorts are needed to validate these results.

Alpha Synuclein: Neurodegeneration and Inflammation.

Alpha-Synuclein (α-Syn) is one of the most important molecules involved in the pathogenesis of Parkinson's disease and related disorders, sy … ned with a lasting peripheral inflammatory effect. The reactivity of microglia was amplified, while astrocytes were damaged by the double stimulus, opening new perspectives for the control of inflammation in synucleinopathies. Starting from our studies in experimental models, we extended the perspective to find useful pointers to orient future research and p …

Inhibition of complement C3 signaling ameliorates locomotor and visual dysfunction in autoimmune inflammatory diseases.

Neuromyelitis optica (NMO) is an autoimmune inflammatory disease of the central nervous system (CNS) characterized by transverse myelitis and optic neuritis. The pathogenic serum IgG antibody against the aquaporin-4 (AQP4) on astrocytes triggers the activation of the complement cascade, causing astrocyte injury, followed by oligodendrocyte injury, demyelination, and neuronal loss. Complement C3 is positioned as a central player that relays upstream initiation signals to activate downstream effectors, potentially stimulating and amplifying host immune and inflammatory responses. However, whethe…

Possible involvement of progranulin in the protective effect of elastase inhibitor on cerebral ischemic injuries of neuronal and glial cells.

In a previous study, we demonstrated that neutrophil elastase is activated in the brain parenchyma after cerebral ischemia, which enzyme cleaves progranulin (PGRN), an anti-inflammatory factor. In that study, we also found that sivelestat, a selective neutrophil elastase inhibitor, attenuates ischemia-induced inflammatory responses. However, it was not clear whether this anti-inflammatory effect was due to the direct effect of sivelestat. In this study, we evaluated the effects of sivelestat or recombinant PGRN (rPGRN) on cell injuries in cultured neurons, astrocytes, and microglia under oxyge…

Tau oligomer induced HMGB1 release contributes to cellular senescence and neuropathology linked to Alzheimer's disease and frontotemporal dementia.

Aging, pathological tau oligomers (TauO), and chronic inflammation in the brain play a central role in tauopathies, including Alzheimer's disease (AD) and frontotemporal dementia (FTD). However, the underlying mechanism of TauO-induced aging-related neuroinflammation remains unclear. Here, we show that TauO-associated astrocytes display a senescence-like phenotype in the brains of patients with AD and FTD. TauO exposure triggers astrocyte senescence through high mobility group box 1 (HMGB1) release and inflammatory senescence-associated secretory phenotype (SASP), which mediates paracrine sene…

Structural Brain Changes during the Neonatal Period in a Rabbit Model of Intrauterine Growth Restriction.

BACKGROUND: Intrauterine growth restriction (IUGR) is associated with abnormal neurodevelopment, but the associated structural brain changes … d, and thereafter, neuronal arborization in the frontal cortex and density of pre-oligodendrocytes, astrocytes, and microglia in the corpus callosum were evaluated. RESULTS: Higher stillbirth in IUGR fetuses together with a reduced birth weight as compared to controls was evidenced. IUGR animals showed poorer functional results, an altered neuronal arboriza …

Autopsy Case of Meningoencephalomyelitis Associated With Glial Fibrillary Acidic Protein Antibody.

BACKGROUND AND OBJECTIVES: To describe the autopsy findings and neuropathologic evaluation of autoimmune meningoencephalomyelitis associated with glial fibrillary acidic protein (GFAP) antibody. METHODS: We reviewed the clinical course, imaging, laboratory, and autopsy findings of a patient with autoimmune meningoencephalomyelitis associated with GFAP antibody who had a refractory course to multiple immunosuppressive therapies. RESULTS: The patient was a 70-year-old man who was diagnosed as GFAP antibody-associated autoimmune meningoencephalomyelitis. MRI of the head showed linear perivascul