Overexpression of Brain- and Glial Cell Line-Derived Neurotrophic Factors Is Neuroprotective in an Animal Model of Acute Hypobaric Hypoxia.

Currently, the role of the neurotrophic factors BDNF and GDNF in maintaining the brain's resistance to the damaging effects of hypoxia and functional recovery of neural networks after exposure to damaging factors are actively studied. The assessment of the effect of an increase in the level of these neurotrophic factors in brain tissues using genetic engineering methods on the resistance of laboratory animals to hypoxia may pave the way for the future clinical use of neurotrophic factors BDNF and GDNF in the treatment of hypoxic damage. This study aimed to evaluate the antihypoxic and neuroprotective properties of BDNF and GDNF expression level increase using adeno-associated viral vectors in modeling hypoxia in vivo.

Interferon-γ augments GABA release in the developing neocortex nitric oxide synthase/soluble guanylate cyclase and constrains network activity.

Interferon-γ (IFN-γ), a cytokine with neuromodulatory properties, has been shown to enhance inhibitory transmission. Because early inhibitory neurotransmission sculpts functional neuronal circuits, its developmental alteration may have grave consequences. Here, we investigated the acute effects of IFN-γ on γ-amino-butyric acid (GABA)ergic currents in layer 5 pyramidal neurons of the somatosensory cortex of rats at the end of the first postnatal week, a period of GABA-dependent cortical maturation.

The Influence of Neurotrophic Factors BDNF and GDNF Overexpression on the Functional State of Mice and Their Adaptation to Audiogenic Seizures.

The high prevalence of diagnosed cases of severe neurological disorders, a significant proportion of which are epilepsy, contributes to a high level of mortality and disability in the population. Neurotrophic factors BDNF and GNDF are considered promising agents aimed at increasing the central nervous system's adaptive potential for the development of the epileptiform activity. Despite the pronounced neuroprotective and anticonvulsant potential, an appropriate way to stimulate these endogenous signaling molecules with minimal risk of side effects remains an open question.

Surgical Management of Intractable Meniere's Disease.

Meniere's Disease (MD) is an inner ear disorder characterized by spontaneous recurrent vertigo, fluctuating sensorineural hearing loss, aural fullness and low-pitch tinnitus. Therapeutic management of MD includes dietary restriction and medical therapy. A minority of cases is characterized by frequent vertigo attacks, progressive hearing loss and persistent tinnitus even through the continuous medical treatments; this condition is called intractable MD and requires a therapeutic escalation from non-invasive medical treatment to surgical intervention.

Nigral neuropathology of Parkinson's motor subtypes coincide with circuitopathies: a scoping review.

The neuropathological substrates of Parkinson's disease (PD) patients with motor subtypes tremor-dominance (TD), non-tremor dominance (nTD), postural instability and gait difficulty (PIGD), and akinetic-rigid (AR) are not completely differentiated. While extensive pathological research has been conducted on neuronal tissue of PD patients, data have not been discussed in the context of mechanistic circuitry theories differentiating motor subtypes. It is, therefore, expected that a more specific and tailored management of PD symptoms can be accomplished by understanding symptom-specific neuropathological mechanisms with the detail histology can provide.

Selenium Status in Paediatric Patients with Neurodevelopmental Diseases.

Neurodevelopmental diseases are often associated with other comorbidities, especially inflammatory processes. The disease may affect the trace element (TE) status, which in turn may affect disease severity and progression. Selenium (Se) is an essential TE required for the biosynthesis of selenoproteins including the transporter selenoprotein P (SELENOP) and extracellular glutathione peroxidase (GPX3).

LTα, TNF, and ILC3 in Peyer's Patch Organogenesis.

TNF and LTα are structurally related cytokines of the TNF superfamily. Their genes are located in close proximity to each other and to the gene within the TNF/LT locus inside MHC. Unlike , transcription of and of is tightly controlled, with the gene being an immediate early gene that is rapidly induced in response to various inflammatory stimuli.

5-Aminolevulinic Acid (5-ALA)-Induced Protoporphyrin IX Fluorescence by Glioma Cells-A Fluorescence Microscopy Clinical Study.

5-aminolevulinic acid (5-ALA)-induced PpIX fluorescence is used by neurosurgeons to identify the tumor cells of high-grade gliomas during operation. However, the issue of whether 5-ALA-induced PpIX fluorescence consistently stains all the tumor cells is still debated. Here, we assessed the cytoplasmatic signal of 5-ALA by fluorescence microscopy in a series of human gliomas.

Disease relevance of rare VPS13B missense variants for neurodevelopmental Cohen syndrome.

Autosomal recessive Cohen syndrome is a neurodevelopmental disorder characterized by postnatal microcephaly, intellectual disability, and a typical facial gestalt. Genetic variants in VPS13B have been found to cause Cohen syndrome, but have also been linked to autism, retinal disease, primary immunodeficiency, and short stature. While it is well established that loss-of-function mutations of VPS13B cause Cohen syndrome, the relevance of missense variants for the pathomechanism remains unexplained.

Nerve Growth Factor (NGF) as Partaker in the Modulation of UV-Response in Cultured Human Conjunctival Fibroblasts.

Corroborating data sustain the pleiotropic effect of nerve growth factor (NGF) in the protection of the visual system from dangerous stimuli, including ultraviolet (UV). Since UV exposure might promote ocular surface changes (conjunctival inflammation and matrix rearrangement), as previously reported from in vivo studies sustaining some protective NGF effects, in vitro cultures of human conjunctival fibroblasts (FBs) were developed and exposed to a single UV exposure over 15 min (0.277 W/m), either alone or supplemented with NGF (1-10-100 ng/mL).

TrkB-dependent EphrinA reverse signaling regulates callosal axon fasciculate growth downstream of Neurod2/6.

Abnormal development of corpus callosum is relatively common and causes a broad spectrum of cognitive impairments in humans. We use acallosal Neurod2/6-deficient mice to study callosal axon guidance within the ipsilateral cerebral cortex. Initial callosal tracts form but fail to traverse the ipsilateral cingulum and are not attracted towards the midline in the absence of Neurod2/6.

Self-Sampled Gargle Water Direct RT-LAMP as a Screening Method for the Detection of SARS-CoV-2 Infections.

We assessed the viability of self-sampled gargle water direct RT-LAMP (LAMP) for detecting SARS-CoV-2 infections by estimating its sensitivity with respect to the gold standard indirect RT-PCR of paired oro-nasopharyngeal swab samples. We also assessed the impact of symptom onset to test time (STT)-i.e.

Modified Zipper Method, a Promising Treatment Option in Severe Pediatric Immune-Mediated Neurologic Disorders.

Objective: To introduce and evaluate a modified version of the "zipper method"-a treatment strategy alternating intravenous immunoglobulin (IVIG) and plasma exchange (PLEX) first reported for 9 pediatric cases of Guillain-Barré syndrome in 2018-for treatment of severe immune-mediated neurologic disorders in children.

Methods: The modified zipper method comprised longer intervals between PLEX-IVIG cycles (48hours instead of 24hours), more cycles (7-10 instead of 5), a consistent plasma volume exchange (instead of the original multistep approach), and variable infusion times for IVIGs (4-8hours). The modified zipper method was applied as an individual treatment approach once standard therapy failed.

TNF hampers intestinal tissue repair in colitis by restricting IL-22 bioavailability.

Successful treatment of chronic inflammatory diseases integrates both the cessation of inflammation and the induction of adequate tissue repair processes. Strikingly, targeting a single proinflammatory cytokine, tumor necrosis factor (TNF), induces both processes in a relevant cohort of inflammatory bowel disease (IBD) patients. However, the molecular mechanisms underlying intestinal repair following TNF blockade during IBD remain elusive.

Magnetic labeling of primary murine monocytes using very small superparamagnetic iron oxide nanoparticles.

Due to their very small size, nanoparticles can interact with all cells in the central nervous system. One of the most promising nanoparticle subgroups are very small superparamagnetic iron oxide nanoparticles (VSOP) that are citrate coated for electrostatic stabilization. To determine their influence on murine blood-derived monocytes, which easily enter the injured central nervous system, we applied VSOP and carboxydextran-coated superparamagnetic iron oxide nanoparticles (Resovist).

Bi-allelic variants in CHKA cause a neurodevelopmental disorder with epilepsy and microcephaly.

The Kennedy pathways catalyse the de novo synthesis of phosphatidylcholine and phosphatidylethanolamine, the most abundant components of eukaryotic cell membranes. In recent years, these pathways have moved into clinical focus because four of ten genes involved have been associated with a range of autosomal recessive rare diseases such as a neurodevelopmental disorder with muscular dystrophy (CHKB), bone abnormalities and cone-rod dystrophy (PCYT1A) and spastic paraplegia (PCYT2, SELENOI). We identified six individuals from five families with bi-allelic variants in CHKA presenting with severe global developmental delay, epilepsy, movement disorders and microcephaly.

Standard values for MRI brain biometry throughout the first year of life.

Background: Brain structures in the infant brain are investigated reliably using cranial magnetic resonance imaging. However, the lack of quantitative standard values for various brain regions results in data interpretation that is often subjective or based on small patient cohorts. The aim of this study was to create simple linear measurements to assess brain structures in infancy.

Cross-sectional Neuromuscular Phenotyping Study of Patients With Arhinia With Variants.

Background And Objectives: Facioscapulohumeral muscular dystrophy type 2 (FSHD2) and arhinia are 2 distinct disorders caused by pathogenic variants in the same gene: . The mechanism underlying this phenotypic divergence remains unclear. In this study, we characterize the neuromuscular phenotype of individuals with arhinia caused by variants and analyze their complex genetic and epigenetic criteria to assess their risk for FSHD2.

Connexin30-Deficiency Causes Mild Hearing Loss With the Reduction of Endocochlear Potential and ATP Release.

and are adjacent genes encoding connexin 26 (Cx26) and connexin 30 (Cx30), respectively, with overlapping expressions in the inner ear. Both genes are associated with the commonest monogenic hearing disorder, recessive isolated deafness DFNB1. Cx26 plays an important role in auditory development, while the role of Cx30 in hearing remains controversial.

Sex-dependent responsiveness of hippocampal neurons to sex neurosteroids: A role of Arc/Arg3.1.

Sex steroids, such as estradiol (E ) and dihydrotestosterone (DHT), regulate hippocampal plasticity and memory in a sex-dependent manner. Because the activity-regulated cytoskeleton protein Arc/Arg3.1 is essential for long-term memory formation and synaptic plasticity, we investigated the expression of Arc/Arg3.

Interferon-γ enhances neocortical synaptic inhibition by promoting membrane association and phosphorylation of GABA receptors in a protein kinase C-dependent manner.

Interferon-γ (IFN-γ), an important mediator of the antiviral immune response, can also act as a neuromodulator. CNS IFN-γ levels rise acutely in response to infection and therapeutically applied IFN-γ provokes CNS related side effects. Moreover, IFN-γ plays a key role in neurophysiological processes and a variety of chronic neurological and neuropsychiatric conditions.

MicroRNA-100-5p and microRNA-298-5p released from apoptotic cortical neurons are endogenous Toll-like receptor 7/8 ligands that contribute to neurodegeneration.

Background: MicroRNA (miRNA) expression in the brain is altered in neurodegenerative diseases. Recent studies demonstrated that selected miRNAs conventionally regulating gene expression at the post-transcriptional level can act extracellularly as signaling molecules. The identity of miRNA species serving as membrane receptor ligands involved in neuronal apoptosis in the central nervous system (CNS), as well as the miRNAs' sequence and structure required for this mode of action remained largely unresolved.