Concerted transcriptional regulation of the morphogenesis of hypothalamic neurons by ONECUT3.

Acquisition of specialized cellular features is controlled by the ordered expression of transcription factors (TFs) along differentiation trajectories. Here, we find a member of the Onecut TF family, ONECUT3, expressed in postmitotic neurons that leave their Ascl1/Onecut1/2 proliferative domain in the vertebrate hypothalamus to instruct neuronal differentiation. We combined single-cell RNA-seq and gain-of-function experiments for gene network reconstruction to show that ONECUT3 affects the polarization and morphogenesis of both hypothalamic GABA-derived dopamine and thyrotropin-releasing hormone (TRH) glutamate neurons through neuron navigator-2 (NAV2).

Tricellulin, α-Catenin and Microfibrillar-Associated Protein 5 Exhibit Concomitantly Altered Immunosignals along with Vascular, Extracellular and Cytoskeletal Elements after Experimental Focal Cerebral Ischemia.

Along with initiatives to understand the pathophysiology of stroke in detail and to identify neuroprotective targets, cell-stabilizing elements have gained increasing attention. Although cell culture experiments have indicated that tricellulin, α-catenin and microfibrillar-associated protein 5 (MFAP5) contribute to cellular integrity, these elements have not yet been investigated in the ischemic brain. Applying immunofluorescence labeling, this study explored tricellulin, MFAP5 and α-catenin in non-ischemic and ischemic brain areas of mice (24, 4 h of ischemia) and rats (4 h of ischemia), along with collagen IV and fibronectin as vascular and extracellular matrix constituents and microtubule-associated protein 2 (MAP2) and neurofilament light chain (NF-L) as cytoskeletal elements.

Combining atomic force microscopy and fluorescence-based techniques to explore mechanical properties of naive and ischemia-affected brain regions in mice.

Knowledge of the brain's structure and function is essential for understanding processes in health and disease. Histochemical and fluorescence-based techniques have proven beneficial in characterizing brain regions and cellular compositions in pre-clinical research. Atomic force microscopy (AFM) has been introduced for mechanical tissue characterization, which may also help investigate pathophysiological aspects in disease-related models such as stroke.

Increasing reproducibility in preclinical stroke research: the correlation of immunofluorescence intensity measurements and Western blot analyses strongly depends on antibody clonality and tissue pre-treatment in a mouse model of focal cerebral ischemia.

In the setting of stroke, ischemia not only impairs neuronal function, but also detrimentally affects the different components of the neurovascular unit, which are shown to be involved in the transition from reversible to long-lasting tissue damage. In this context, the glial proteins myelin basic protein (MBP) and the 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNP) as well as the vasculature-associated basement membrane proteins laminin and collagen IV have been identified as ischemia-sensitive elements. However, available data from immunofluorescence and Western blot analyses are often found to be contradictory, which renders interpretation of the respective data rather difficult.

Cerebrospinal Fluid Protein Concentrations in Hydrocephalus.

CSF protein levels are altered in neurological disorders, such as hydrocephalus of different etiologies. In this retrospective observational study, we analyzed cerebrospinal fluid (CSF) samples in hydrocephalic diseases such as aqueductal stenosis (AQS, = 27), normal pressure hydrocephalus (NPH, = 24), hydrocephalus communicans (commHC, = 25) and idiopathic intracranial hypertension (IIH)/pseudotumor cerebri (PC, = 7) in comparison with neurological patients without hydrocephalic configuration (control, = 95). CSF was obtained through CSF diversion procedures and lumbar punction and analyzed for protein concentrations according to the institution's laboratory standards.

Changes in CSF Surface Tension in Relation to Surfactant Proteins in Children with Intraventricular Hemorrhage.

The regulation of surface tension (ST) by surfactants plays an important role in the human respiratory system but is largely unexplored in brain homeostasis. The aim of this study was to evaluate changes in ST in relation to surfactant proteins (SPs) in children with intraventricular hemorrhage (IVH). CSF samples from 93 patients were analyzed for ST with a force tensiometer and SP-A-D and -G with ELISA assays.

Retrosplenial cortex microglia and perineuronal net densities are associated with memory impairment in aged rhesus macaques.

Synapse loss and altered plasticity are significant contributors to memory loss in aged individuals. Microglia, the innate immune cells of the brain, play critical roles in maintaining synapse function, including through a recently identified role in regulating the brain extracellular matrix. This study sought to determine the relationship between age, microglia, and extracellular matrix structure densities in the macaque retrosplenial cortex.

Diffusion Weighted Imaging in Gliomas: A Histogram-Based Approach for Tumor Characterization.

(1) Background: Astrocytic gliomas present overlapping appearances in conventional MRI. Supplementary techniques are necessary to improve preoperative diagnostics. Quantitative DWI via the computation of apparent diffusion coefficient (ADC) histograms has proven valuable for tumor characterization and prognosis in this regard.

Regionally Altered Immunosignals of Surfactant Protein-G, Vascular and Non-Vascular Elements of the Neurovascular Unit after Experimental Focal Cerebral Ischemia in Mice, Rats, and Sheep.

The surfactant protein-G (SP-G) has recently been discovered in the brain and linked to fluid balance regulations. Stroke is characterized by impaired vessel integrity, promoting water influx and edema formation. The neurovascular unit concept (NVU) has been generated to cover not only ischemic affections of neurons or vessels but also other regionally associated cells.

Update on Perineuronal Net Staining With Agglutinin (WFA).

As chemically specialized forms of the extracellular matrix in the central nervous system, polyanionic perineuronal nets (PNs) contain diverse constituents, including chondroitin sulfate proteoglycans (CSPGs), hyaluronic acid, and tenascins. They are detectable by various histological approaches such as colloidal iron binding and immunohistochemical staining to reveal, for instance, the CSPGs aggrecan, neurocan, phosphacan, and versican. Moreover, biotin, peroxidase, or fluorescein conjugates of the lectins agglutinin and soybean agglutinin enable the visualization of PNs.

SOAT1: A Suitable Target for Therapy in High-Grade Astrocytic Glioma?

Targeting molecular alterations as an effective treatment for isocitrate dehydrogenase-wildtype glioblastoma (GBM) patients has not yet been established. Sterol-O-Acyl Transferase 1 (SOAT1), a key enzyme in the conversion of endoplasmic reticulum cholesterol to esters for storage in lipid droplets (LD), serves as a target for the orphan drug mitotane to treat adrenocortical carcinoma. Inhibition of SOAT1 also suppresses GBM growth.

Surfactant Protein-G in Wildtype and 3xTg-AD Mice: Localization in the Forebrain, Age-Dependent Hippocampal Dot-like Deposits and Brain Content.

The classic surfactant proteins (SPs) A, B, C, and D were discovered in the lungs, where they contribute to host defense and regulate the alveolar surface tension during breathing. Their additional importance for brain physiology was discovered decades later. SP-G, a novel amphiphilic SP, was then identified in the lungs and is mostly linked to inflammation.

Surfactant protein C is associated with perineuronal nets and shows age-dependent changes of brain content and hippocampal deposits in wildtype and 3xTg mice.

Surfactant protein C (SP-C) modulates cerebrospinal fluid (CSF) rheology. During ageing, its declining levels are accompanied by an increased burden of white matter lesions. Pulmonary SP-C intermediates harbouring the BRICHOS-domain prevent protein misfolding in the lungs.

First Experience of Three Neurovascular Centers With the p64MW-HPC, a Low-Profile Flow Diverter Designed for Proximal Cerebral Vessels With Antithrombotic Coating.

In the last decade, flow diversion (FD) has been established as hemodynamic treatment for cerebral aneurysms arising from proximal and distal cerebral arteries. However, two significant limitations remain-the need for 0.027" microcatheters required for delivery of most flow diverting stents (FDS), and long-term dual anti-platelet therapy (DAPT) in order to prevent FDS-associated thromboembolism, at the cost of increasing the risk for hemorrhage.

Flow Diversion for Reconstruction of Intradural Vertebral Artery Dissecting Aneurysms Causing Subarachnoid Hemorrhage-A Retrospective Study From Four Neurovascular Centers.

Dissecting aneurysms (DAs) of the vertebrobasilar territory manifesting with subarachnoid hemorrhage (SAH) are associated with significant morbi-mortality, especially in the case of re-hemorrhage. Sufficient reconstruction of the affected vessel is paramount, in particular, if a dominant vertebral artery (VA) is impacted. Reconstructive options include stent-assisted coiling and flow diversion (FD).

The Cytoskeletal Elements MAP2 and NF-L Show Substantial Alterations in Different Stroke Models While Elevated Serum Levels Highlight Especially MAP2 as a Sensitive Biomarker in Stroke Patients.

In the setting of ischemic stroke, the neurofilament subunit NF-L and the microtubule-associated protein MAP2 have proven to be exceptionally ischemia-sensitive elements of the neuronal cytoskeleton. Since alterations of the cytoskeleton have been linked to the transition from reversible to irreversible tissue damage, the present study investigates underlying time- and region-specific alterations of NF-L and MAP2 in different animal models of focal cerebral ischemia. Although NF-L is increasingly established as a clinical stroke biomarker, MAP2 serum measurements after stroke are still lacking.

New Mechanistic Insights, Novel Treatment Paradigms, and Clinical Progress in Cerebrovascular Diseases.

The past decade has brought tremendous progress in diagnostic and therapeutic options for cerebrovascular diseases as exemplified by the advent of thrombectomy in ischemic stroke, benefitting a steeply increasing number of stroke patients and potentially paving the way for a renaissance of neuroprotectants. Progress in basic science has been equally impressive. Based on a deeper understanding of pathomechanisms underlying cerebrovascular diseases, new therapeutic targets have been identified and novel treatment strategies such as pre- and post-conditioning methods were developed.

Increased Immunosignals of Collagen IV and Fibronectin Indicate Ischemic Consequences for the Neurovascular Matrix Adhesion Zone in Various Animal Models and Human Stroke Tissue.

Ischemic stroke causes cellular alterations in the "neurovascular unit" (NVU) comprising neurons, glia, and the vasculature, and affects the blood-brain barrier (BBB) with adjacent extracellular matrix (ECM). Limited data are available for the zone between the NVU and ECM that has not yet considered for neuroprotective approaches. This study describes ischemia-induced alterations for two main components of the neurovascular matrix adhesion zone (NMZ), i.

CSF Surfactant Protein Changes in Preterm Infants After Intraventricular Hemorrhage.

Surfactant proteins (SP) have been shown to be inherent proteins of the human CNS and are altered during acute and chronic disturbances of CSF circulation. Aim of the study was to examine the changes of surfactant protein concentrations in CSF of preterm babies suffering from intraventricular hemorrhage. Consecutive CSF samples of 21 preterm infants with intraventricular hemorrhages (IVH) and posthemorrhagic hydrocephalus (PHHC) were collected at primary intervention, after 5-10 days and at time of shunt insertion ~50 days after hemorrhage.

Increased expression of heme-binding protein 1 early in Alzheimer's disease is linked to neurotoxicity.

Alzheimer's disease is the most prevalent neurodegenerative disorder leading to progressive cognitive decline. Despite decades of research, understanding AD progression at the molecular level, especially at its early stages, remains elusive. Here, we identified several presymptomatic AD markers by investigating brain proteome changes over the course of neurodegeneration in a transgenic mouse model of AD (3×Tg-AD).

Simultaneous alterations of oligodendrocyte-specific CNP, astrocyte-specific AQP4 and neuronal NF-L demarcate ischemic tissue after experimental stroke in mice.

Ischemic stroke not only affects neurons, but also glial and vascular elements. The development of novel neuroprotective strategies thus requires an improved pathophysiological understanding of ischemia-affected cell types that comprise the 'neurovascular unit' (NVU). To explore spatiotemporal alterations of oligodendrocytes, astrocytes and neurons after experimental ischemic stroke, we applied a permanent middle cerebral artery occlusion model in mice for 4 and 24 h.

Rheologically Essential Surfactant Proteins of the CSF Interacting with Periventricular White Matter Changes in Hydrocephalus Patients - Implications for CSF Dynamics and the Glymphatic System.

Surfactant proteins (SP) are multi-systemic proteins playing crucial roles in the regulation of rheological properties of physiological fluids, host defense, and the clearance of potentially harmful metabolites. Hydrocephalus patients suffer from disturbed central nervous system (CNS) fluid homeostasis and exhibit remarkably altered SP concentrations within the cerebrospinal fluid (CSF). A connection between CSF-SPs, CSF flow, and ventricular dilatation, a morphological hallmark of hydrocephalus, has been reported previously.

Transcriptional Response and Morphological Features of the Neurovascular Unit and Associated Extracellular Matrix After Experimental Stroke in Mice.

Experimental stroke studies yielded insights into single reactions of the neurovascular unit (NVU) and associated extracellular matrix (ECM). However, the extent of simultaneous processes caused by ischemia and their underlying transcriptional changes are still poorly understood. Strictly following the NVU and ECM concept, this study explored transcriptional responses of cellular and non-cellular components as well as their morphological characteristics following ischemia.

Primary brain amyloidoma, both a neoplastic and a neurodegenerative disease: a case report.

Background: Scattered extracellular deposits of amyloid within the brain parenchyma can be found in a heterogeneous group of diseases. Its condensed accumulation in the white matter without evidence for systemic amyloidosis is known as primary brain amyloidoma (PBA). Although originally considered as a tumor-like lesion by its space-occupying effect, this condition displays also common hallmarks of a neurodegenerative disorder.