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Summary This Good Practice Paper provides recommendations for the baseline investigation, risk stratification and use of prophylactic interventions for patients with large B‐cell lymphoma at risk of central nervous system relapse. Recent evidence which has questioned the role of high‐dose methotrexate in this clinical scenario is discussed in detail. [ABSTRACT FROM AUTHOR]

Conjugated polymer of poly(fluorene-co-quinoxaline) was synthesized via Suzuki coupling polymerization. The emission color of the polymer can be tuned depending on the concentration of the polymer in solution. A low-energy bandgap is observed both in the concentrated solution and in the solid state, caused by aggregation of the polymer chains, resulting in long wavelength emission from the quinoxaline moiety, while short wavelength emission can be seen in diluted, well-dissolved solution. The presence of quinoxaline units enables us to demonstrate fluorescence switching and imaging. Paper-based strips containing the polymer are prepared via simple immersion of filter paper in the polymer solution for practical use in the detection of nerve agents. The emission of the paper-based strip is quenched upon exposure to diethyl chlorophosphate (DCP), a nerve agent simulant, and the initial emission intensity can be almost restored by treatment with aqueous sodium hydroxide solution, making a possible reversible paper-based sensor.

The results of comparative morphological and ultrastructural research of the synaptic organization of spinal cord motoneurons from fishes, amphibian, reptiles and mammals are presented in the review. Fundamental regularities of the formation of the synaptic organization of motoneurons in vertebrate phylogenesis were established. The results of electron microscopical analysis showed that all basic elements of the synaptic ultrastructure preserved in the motoneuronal synapse of vertebrates during the evolution. On the basis of large experimental material it was found that the synaptic organization of individual motoneuron as a whole underwent structural reorganization, presented as corresponding transformations in mechanisms of the synaptic transmission.

The present paper summarizes the proposed time-dependent sensitization (TDS) and partial limbic kindling model for illness from low-level chemicals; reviews and critiques prior studies on CNS aspects of multiple chemical sensitivity (MCS); and outlines possible experimental approaches to future studies. TDS is the progressive and persistent amplification of behavioral, neurochemical, endocrine, and/or immunological responses to repeated intermittent stimuli over time. Partial limbic kindling is a progressive and persistent lowering of the threshold for eliciting electrical afterdischarges, but not motor seizures, in certain brain structures such as amygdala and hippocampus; behavioral consequences include increased avoidant behaviors. The focus of the paper is the controversial claim of altered sense of smell and illness from low levels of environmental chemicals (i.e., "cacosmia"), levels that should not have any biologically harmful effects by the rules of classical neurotoxicology. A major perspective of this paper is that the phenomenology of MCS is similar to that of time-dependent sensitization (reverse tolerance) and tolerance as studied in the substance abuse literature. The TDS model for MCS proposes that neurobiological amplification underlies the symptoms and phenomenology of these patients, including their behavioral features of heightened affective and somatic distress. It is hypothesized that MCS patients, who are mostly women, may be individuals who sensitize to substances rapidly and to the extreme, to the point of aversive symptomatology with less complete capacity for development of tolerance. Possible parallels between MCS and TDS include: (a) initiation by single or multiple intermittent stimuli; (b) lasting changes in subsequent reactivity to low levels of chemically unrelated substances; (c) cross-sensitization between the stressors and pharmacological agents; (d) greater vulnerability of individuals who are female, who have certain genetic characteristics, and/or who may be hyperreactive to novelty (cf. trait shyness); (e) lack of obvious differences between sensitized and unsensitized individuals at baseline without eliciting exposures; (f) bidirectionality (bipolarity) of sensitized responses; (g) both context-dependent (conditioned) and context-independent (unconditioned) amplification of responses. To minimize variability between studies, research in this area needs (a) consensus on a working case definition of MCS or at least of cacosmia as a specific symptom in a subset of well-defined medical and psychiatric disorders; and (b) proper design of chemical challenge studies in MCS, controlling for individual differences in sensitizability and for the properties of sensitization (e.g., repeated intermittent exposure tests) and tolerance (e.g., removal from customary ambient air exposures prior to testing).

Myeloid cells in the central nervous system (CNS), such as microglia, CNS-associated macrophages (CAMs), dendritic cells and monocytes, are vital for steady-state immune homeostasis as well as the resolution of tissue damage during brain development or disease-related pathology. The complementary usage of multimodal high-throughput and high-dimensional single-cell technologies along with recent advances in cell-fate mapping has revealed remarkable myeloid cell heterogeneity in the CNS. Despite the establishment of extensive expression profiles revealing myeloid cell multiplicity, the local anatomical conditions for the temporal- and spatial-dependent cellular engraftment are poorly understood. Here we highlight recent discoveries of the context-dependent mechanisms of myeloid cell migration and settlement into distinct subtissular structures in the CNS. These insights offer better understanding of the factors needed for compartment-specific myeloid cell recruitment, integration and residence during development and perturbation, which may lead to better treatment of CNS diseases., (© 2023. Springer Nature America, Inc.)

The blood–brain barrier (BBB) protects the central nervous system from toxins and pathogens in the blood by regulating permeation of molecules through the barrier interface. In vitro BBB models described to date reproduce some aspects of BBB functionality, but also suffer from incomplete phenotypic expression of brain endothelial traits, difficulty in reproducibility and fabrication, or overall cost. To address these limitations, a 3D BBB model based on a hybrid paper/nanofiber scaffold is described. The cell culture platform utilizes lens paper as a framework to accommodate 3D culture of astrocytes. An electrospun nanofiber layer is coated onto one face of the paper to mimic the basement membrane and support growth of an organized 2D layer of endothelial cells (ECs). Human induced pluripotent stem cell‐derived ECs and astrocytes are co‐cultured to develop a human BBB model. Morphological and spatial organization of model are validated with confocal microscopy. Measurements of transendothelial resistance and permeability demonstrate the BBB model develops a high‐quality barrier and responds to hyperosmolar treatments. RNA‐sequencing shows introduction of astrocytes both regulates EC tight junction proteins and improves endothelial phenotypes related to vasculogenesis. This model shows promise as a model platform for future in vitro studies of the BBB. [ABSTRACT FROM AUTHOR]

The Phenylketonuria (PKU) is an inborn defect of phenylalanine (Phe) metabolism, in which Phe accumulated in the blood causing alterations at the central nervous system. Therefore, the detection of PKU is very important for the early diagnosis of PKU patients. However, existing tests for PKU are time-consuming and require high-resource laboratories. In this study, a novel paper-based biosensor based on phenylalnine ammonia lyase (PAL) hybrid nanoflowers was constructed that provides a semi-quantitative output of the concentration of Phe from urine samples. PAL@Ca 3 (PO 4) 2 hybrid nanoflowers (PAL@NF) were first prepared using PAL and Ca2+. Synthesis conditions of the PAL@NF on the formation of the PAL@NF were optimized. The PAL@NF exhibited 90% activity recovery under optimal condition. Compared with free PAL, the PAL@NF displayed good storage stability and increased tolerance to proteolysis. After five consecutive operating cycles, the PAL@NF still retained 73% of its initial activity, indicating excellent reusability. Furthermore, the paper-based biosensor was able to detect Phe concentration in urine samples, and exhibited good linearity to the Phe concentrations in the range from 60 to 2400 μM and the response time was only about 10 min. Therefore, the paper-based biosensor can be a promising candidate as a biosensor for the detection of PKU. Unlabelled Image • PAL@Ca 3 (PO 4) 2 hybrid nanoflowers were successfully synthesized. • The PAL@Ca 3 (PO 4) 2 hybrid nanoflowers exhibited high activity and stability. • A paper-based biosensor based on the PAL hybrid nanoflowers for urinary Phe measurement was constructed for the first time. • The paper-based biosensor is expected to become a home-test monitoring for PKU. [ABSTRACT FROM AUTHOR]

Sir Louis Francis Knuthsen (1869–1957), the physician who painstakingly listed almost all treatments known for obstinate hiccough, ascribes the holding of breath method to Philip Henry Pye-Smith, FRS (1840–1914), consultant at Guy's Hospital in London. In fact, the strategy is much older and was mentioned by greats such as Francis Bacon (1561–1626), Aristoteles (384–322 BC), and Eryximachus (late-fifth century bce). Hypoventilation to reduce central nervous system excitability was used in antiquity as evidenced by Cyriacus' treatment of Artemia, the daughter of Emperor Diocletian (≈ 244–311). She was suffering from (among others) seizures that Cyriacus was apparently controlling by tightening a scarf around her neck, as depicted by Mathias Grünewald (1460–1528) on a wing of the so-called Heller Altar now on display at the Historical Museum, Frankfurt, Germany. In modern times, around 1920, inducing hypercapnia by CO2 inhalation as therapy for hiccups was suggested and tried by a number of anesthetists, such as Americans Russel Firth Sheldon (1885–1960) and Brian Collins Sword (1889–1956) in Boston; Briton Christopher Langton Hewer (1896–1986) at St. Bartholomew's Hospital in London; Austrian Karl Doppler (1887–1947) in Vienna; and the German/Polish Arthur Dzialoszynski (1893–1977) in Berlin. Although various authors assign the scientific primate to any of them, the first mention of carbon dioxide inhalation as treatment of singultus in the scientific literature is of French origin and was made by Paris pharmacist Henri Bocquillon-Limousin (1856–1917) in his 1892 Formulaire des médicaments nouveaux et des médications nouvelles. [ABSTRACT FROM AUTHOR]

Introduction: Primary Diffuse Large B Cell Lymphoma of CNS (PCNSL) is a rare variant of Diffuse Large B Cell Lymphoma (DLBCL) and presents with an aggressive clinical course and usually resistant to commonly used therapy regimens. Recently, role of immune checkpoint molecules including PD-1 and PD-L1 confirmed in some solid tumors and lymphoma resulting tumor cells escape the immune system and help to survive and to spread. Inhibitors of PD-1 and PD-L1 have shown lasting responses in several solid and some hematological tumors, while limited studies evaluate checkpoint molecules on PCNSL. Method: In this study, we investigated PD-1 and PD-L1 expression by immunostaining on 71 patients with PCNSL and correlation with demographic data, location of the tumor, proliferation rate, cell of origin, and CD8 positive T cell infiltration in tumor microenvironment. Results: 16 from71 showed PD-1 expression, while PD-L1 expression were 42/71. No association was determined between PD-1/PD-L1 expression and gender, cell of origin, and proliferation rate, but a highly significant difference was determined between the infiltration of CD8 positive T cells in two groups of PD-1/PD-L1 positive and negative. Conclusion: This study revealed expression of check point molecules in remarkable number of PCNSL which may open new therapeutic recommendations in this aggressive lymphoma type. [ABSTRACT FROM AUTHOR]

Restoration of damaged central nervous system structures, functional recovery, and prevention of neuronal loss during neurodegenerative diseases are major objectives in cerebellar research. The highly organized anatomical structure of the cerebellum with numerous inputs/outputs, the complexity of cerebellar functions, and the large spectrum of cerebellar ataxias render therapies of cerebellar disorders highly challenging. There are currently several therapeutic approaches including motor rehabilitation, neuroprotective drugs, non-invasive cerebellar stimulation, molecularly based therapy targeting pathogenesis of the disease, and neurotransplantation. We discuss the goals and possible beneficial mechanisms of transplantation therapy for cerebellar damage and its limitations and factors determining outcome. [ABSTRACT FROM AUTHOR]

Introduction: Position sense, one of the most accurate senses in the body, makes everyone aware of the state of the body in space. This sense is an essential ability in maintaining physical health and avoiding injury. Deficits in position sense cause balance impairments in people with mild Multiple Sclerosis (MS). Position sense requires instant and coordinated communication between the central nervous system and peripheral nervous system, while in patients with MS, communication between the brain and other parts of the body is disrupted. This study aims to compare the position sense of knee joint in people with MS and healthy subjects. Materials and Methods: Ten healthy subjects with the Mean±SD age of 27.6±3.71 years and 10 persons with MS disease and the Mean±SD age of 31.40±3.50 years participated in this study. For evaluating their position sense of knee joint, they flexed their knees (from 90 to 45 degrees) four times, and then a software calculated their repositioning errors. Results: No significant changes in repositioning errors (constant, variable, absolute) were observed in MS patients, and the control group (P˃0.05). Conclusion: The results indicate that mild MS disease cannot disturb the position sense of knee joint. [ABSTRACT FROM AUTHOR]

Intravenously injected [1,2-3H]deoxycorticosterone (DOC) readily enters all parts of the central nervous system. In intact and eviscerated rats the highest concentration of radioactive label was recovered from areas corresponding to the reticular formation from the brain stem. In addrenalectomized animals, in addition to high brain stem concentration, there was also a marked increase in the uptake of radioactivity in the septum, hippocampus and pituitary. Data from the eviscerated rat point to a uniform distribution of [1,2-3H]DOC in neural tissues and suggest that the higher levels of radioactivity found in the brain stem may be due to a DOC metabolite with the chromatographic characteristics of allo-tetrahydro-DOC, an anaesthetic-type steroid. A decrease in the amplitude of evoked sciatic potentials in brain stem sites but not in the thalamic relay nucleus was observed in 52% of the cases studied, following the i.v. injection of 100-150 mug DOC.

After scanning the patient, the data processing presented here follows. First, we must convert 'Dicom' files to 'nifti' files. Then, we need eddy correction (movement to correct distorted photos). After this we use B vectors correction and use MATLAB program, also we use MATLAB for PI, which means background noise correction. For masking we use FSL program, in order to obtain a correct size of brain and finally we use 'MainExploreDTI' to see the direction of fibers. [ABSTRACT FROM AUTHOR]

Recent transcriptomic, histological and functional studies have begun to shine light on the fibroblasts present in the meninges, choroid plexus and perivascular spaces of the brain and spinal cord. Although the origins and functions of CNS fibroblasts are still being described, it is clear that they represent a distinct cell population, or populations, that have likely been confused with other cell types on the basis of the expression of overlapping cellular markers. Recent work has revealed that fibroblasts play crucial roles in fibrotic scar formation in the CNS after injury and inflammation, which have also been attributed to other perivascular cell types such as pericytes and vascular smooth muscle cells. In this Review, we describe the current knowledge of the location and identity of CNS perivascular cell types, with a particular focus on CNS fibroblasts, including their origin, subtypes, roles in health and disease, and future areas for study., (© 2021. Springer Nature Limited.)

We revisit the concept of synergy based on the recently translated classical book by Nikolai Bernstein (On the construction of movements, Medgiz, Moscow 1947; Latash, Bernstein's Construction of Movements, Routledge, Abingdon 2020b) and progress in understanding the physics and neurophysiology of biological action. Two aspects of synergies are described: organizing elements into stable groups (modes) and ensuring dynamical stability of salient performance variables. The ability of the central nervous system to attenuate synergies in preparation for a quick action-anticipatory synergy adjustments-is emphasized. Recent studies have demonstrated synergies at the level of hypothetical control variables associated with spatial referent coordinates for effectors. Overall, the concept of synergies fits naturally the hierarchical scheme of control with referent coordinates with an important role played by back-coupling loops within the central nervous system and from peripheral sensory endings. Further, we review studies showing non-trivial changes in synergies with development, aging, fatigue, practice, and a variety of neurological disorders. Two aspects of impaired synergic control-impaired stability and impaired agility-are introduced. The recent generalization of the concept of synergies for non-motor domains, including perception, is discussed. We end the review with a list of unresolved and troubling issues., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction and aim. Parkinson's disease (PD) is a neurodegenerative condition with motor (e.g. tremor, rigidity, balance disorders, etc.) and non-motor (e.g. cognitive dysfunction, sensory disturbances, etc.) symptoms. According to the WHO, disability due to PD is growing much faster than for other neurological disorders. The incidence has doubled in the last 25 years. In 2019, there were nearly 8.5 million Parkinson's patients worldwide. Although the mechanism of PD is not fully understood, the relationship between alpha-synuclein accumulation in central nervous system and the pathogenesis of this disease (as well as other synucleinopathies) has been strongly confirmed. The aim of this study will be to discuss the influence of alphaSyn on microglia and thus inducing an inflammatory response, as well as the recent discoveries regarding anti-alpha Syn antibodies, such as BIIB054 and PRX002. Material and methods. Review paper based on scientific articles published in different medical database. Analysis of literature. alphaSyn is found in neuronal cell bodies, synapses or glial cells. Their damage may contribute to release of alphaSyn which then is accumulated and invokes the activation of NLRP3 inflammasomes in microglia. NLRP3 inflammasome promotes activation of caspase-1, which in turn mediates maturation and release of proinflammatory cytokines, including interleukin-1 beta and Il-18. Surprisingly, the studies show that alpha Syn-antibody complexes enhances Il-1 beta secration rather than suppresses which closes ways of treatment. Conclusion. These findings set new ways to diagnose PD and are critical to the development of new treatments for the disease. The study will present both clinical and preclinical findings, which may represent promising strategies for the treatment of PD. [ABSTRACT FROM AUTHOR]

In 1935 two young neurologists, Derek Denny-Brown and E. Graeme Robertson, published an article explaining the mechanisms underlying human defaecation based on a manometric study in patients with sacral root and spinal cord lesions, and normal subjects. This article is still routinely cited in studies of rectal and sphincter ani function. Unfortunately, however, the article itself is not written well, being composed of long convoluted sentences and containing 79 often indecipherable figures. Difficult-to-understand articles were common to the publications of Denny-Brown, who became one of the most prominent neurologists of the twentieth century. In accord with our prior work explaining Denny-Brown and Robertson's earlier paper on micturition, we provide here what we hope is a clear explanation of the methods and results in their study on defaecation. [ABSTRACT FROM AUTHOR]

Stroke is a significant disability and death cause worldwide and is conventionally defined as a neurological impairment relating to the intense focal harm of the central nervous system (CNS) by vascular causative components. Although the applicability of robotic rehabilitation is a topic with considerable practical significance because it has produced noticeably higher improvements in motor function than regular (physical and occupational) therapy and exempted the therapists, most of the existing bibliometric papers were not focused on stroke survivors. Additionally, a modular system is designed by joining several medical end-effector devices to a single limb segment, which addresses the issue of potentially dangerous pathological compensatory motions. Searching the Web of Science database, 31,930 papers were identified, and using the VOSviewer software and science mapping technology, data were extracted on the most prolific countries, the connections between them, the most valuable journals according to certain factors, their average year of publication, the most influential papers, and the most relevant topical issues (bubble map of term occurrence). The most prolific country in the analyzed field and over the entire period evaluated (1975–2022) is the United States, and the most prolific journal is Neurorehabilitation and Neural Repair, observing a marked increase in the three periods of scientific interest for this field. The present paper assesses numerous scientific publications to provide, through statistical interpretation of the data, a detailed description of the use of robotic rehabilitation in stroke survivors. The findings may aid scientists, academics, and clinicians in establishing precise goals in the optimization of the management of stroke survivors via robotic rehabilitation, but also through easier access to scientifically validated literature. [ABSTRACT FROM AUTHOR]

Among the myeloid cells in the central nervous system (CNS) microglia are the main representatives of the innate immune system. Microglial fulfil tasks beyond phagocytosing debris and host defense against invading microorganism. During brain development microglia guide for example neurons for proper CNS formation, in adulthood they maintain tissue homeostasis and in aging microglia may become pro-inflammatory and finally exhausted. Recently, several endogenous and exogenous factors were identified that essentially shape the microglial phenotype during both steady-state and pathological conditions. On the one hand, microglia receive inputs from CNS-endogenous sources for example, via crosstalk with other glial cells and neurons but on the other hand microglia are also highly modulated by external signals. Among them, host microbiota-the host's resident bacteria-are vital regulators of the CNS innate immune system. This review summarizes key extrinsic and intrinsic factors, with special focus on the host microbiota, that essentially influence microglia functions and states during development, homeostasis, and disease., (© 2020 Wiley Periodicals, Inc.)

Introduction and aim. Mesenchymal stem cells (MSCs) have been identified in almost all tissue of the human body. It has been demonstrated that they are capable of immunomodulation, self-renewal, and differentiation. As a result, they have been used in cell therapy, regenerative medicine, and tissue engineering. Material and methods. Review of the current literature was conducted using PubMed, ScienceDirect and Google Scholar. Analysis of literature. A wide variety of immunomodulatory and neurotrophic factors are produced and released by MSCs. There is growing evidence that they are effective at repairing damaged tissues within the nervous system. The growth factors released by MSCs, such as IGF and VEGF, are likely to limit the apoptosis of neurons and increase the proliferation of progenitor cells. Additionally, they are more frequently used in regenerative medicine because of their adaptive potential. Conclusion. Mesenchymal stem cells affect neuroprotection and neuroregeneration through their immunomodulatory properties. Cellular interactions and trophic factor release make them valuable tools in clinical therapy. It is believed that MSCs may show therapeutic potential in the treatment of neurodegenerative and inflammatory diseases of the nervous system, as well as structural damage to the nervous system. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are small noncoding RNAs that direct post-transcriptional repression of protein-coding genes. In vertebrates, each highly conserved miRNA typically regulates hundreds of target mRNAs. However, the precise relationship between expression of the miRNAs and that of their targets has remained unclear, in part because of the scarcity of quantitative expression data at cellular resolution. Here we report quantitative analyses of mRNA levels in miRNA-expressing cells of the zebrafish embryo, capturing entire miRNA expression domains, purified to cellular resolution using fluorescent-activated cell sorting (FACS). Focus was on regulation by miR-206 and miR-133 in the developing somites and miR-124 in the developing central nervous system. Comparison of wild-type embryos and those lacking miRNAs revealed predicted targets that responded to the miRNAs and distinguished miRNA-mediated mRNA destabilization from other regulatory effects. For all three miRNAs examined, expression of the miRNAs and that of their predicted targets usually overlapped. A few targets were expressed at higher levels in miRNA-expressing cells than in the rest of the embryo, demonstrating that miRNA-mediated repression can act in opposition to other regulatory processes. However, for most targets expression was lower in miRNA-expressing cells than in the rest of the embryo, indicating that miRNAs usually operate in concert with the other regulatory machinery of the cell. [ABSTRACT FROM AUTHOR]

The distribution of neuropeptide Y (NPY) Y1 receptor-like immunoreactivity (Y1R-LI) has been studied in detail in the CNS of rat using a rabbit polyclonal antibody against the C-terminal 13 amino acids of the rat receptor protein. The indirect immunofluorescence technique with tyramide signal amplification has been employed. For specificity and comparative reasons Y1 knock-out mice and wild-type controls were analyzed. The distribution of Y1R mRNA was also studied using in situ hybridization. A limited comparison between Y1R-LI and NPY-LI was carried out.A widespread and abundant distribution of Y1R-LI, predominantly in processes but also in cell bodies, was observed. In fact, Y1R-LI was found in most regions of the CNS with a similar distribution pattern between rat and wild-type mouse. This staining was specific in the sense that it was absent in adjacent sections following preadsorption of the antibody with 10−5 M of the antigenic peptide, and that it could not be observed in sections of the Y1 KO mouse. In contrast, the staining obtained with an N-terminally directed Y1R antiserum did not disappear, strongly suggesting unspecificity. In brief, very high levels of Y1R-LI were seen in the islands of Calleja, the anterior olfactory nucleus, the molecular layer of the dentate gyrus, parts of the habenula, the interpeduncular nucleus, the mammillary body, the spinal nucleus of the trigeminal, caudal part, the paratrigeminal nucleus, and superficial layers of the dorsal horn. High levels were found in most cortical areas, many thalamic nuclei, some subnuclei of the amygdaloid complex, the hypothalamus and the nucleus of the stria terminalis, the nucleus of the solitary tract, the parabrachial nucleus, and the inferior olive. Moderate levels of Y1R-LI were detected in the cornu Ammonis and the subicular complex, many septal, some thalamic and many brainstem regions. Y1R staining of processes, often fiber and/or dot-like, and occasional cell bodies was also seen in tracts, such as the lateral lemniscus, the rubrospinal tract and the spinal tract of the trigeminal. There was in general a good overlap between Y1R-LI and NPY-LI, but some exceptions were found. Thus, some areas had NPY innervation but apparently lacked Y1Rs, whereas in other regions Y1R-LI, but no or only few NPY-positive nerve endings could be detected.Our results demonstrate that NPY signalling through the Y1R is common in the rat (and mouse) CNS. Mostly the Y1R is postsynaptic but there are also presynaptic Y1Rs. Mostly there is a good match between NPY-releasing nerve endings and Y1Rs, but ‘volume transmission’ may be ‘needed’ in some regions. Finally, the importance of using proper control experiments for immunohistochemical studies on seven-transmembrane receptors is stressed. [Copyright &y& Elsevier]

Introduction and aim. Parkinson's disease is one of the most common neurodegenerative diseases of the central nervous system, mainly affecting the elderly. Symptoms usually appear around the age of 60, before the age of 50 it is rare, while beyond this age the risk of the disease increases by 9% with each decade. The clinical picture is characterized by bradykinesia, rigidity, tremors, postural instability, gait disturbance, and extra- articular symptoms such as anxiety, depression, psychosis, sleep disturbance, salivation, dysphagia. Description of the case. The case report includes a 46-year-old female patient referred to the Neurology Department with suspected Wilson's disease. An ophthalmologic examination prior to hospitalization revealed the presence of a Kayser-Fleischer ring. The woman had been complaining of motor deterioration, fluctuating tremors of the right upper and lower limbs for about 2 years. Physical examination also revealed unsteady increased tension in the right upper limb. Genetic testing and expanded laboratory diagnostics excluded Wilson's disease. An MRI of the head was performed, which detected areas of nonspecific demyelination in periventricular and subcortical locations. Further diagnostics included a DaTSCAN imaging, which confirmed Young -- Onset Parkinson's Disease (YOPD). Conclusion. The differential diagnosis should consider dementia with Lewy bodies, Multiple System Atrophy (MSA), Wilson's Disease (WD), Progressive Supranuclear Palsy (PSP), Corticobasal Degeneration (CBD), spontaneous tremor and secondary Parkinsonian syndromes. The presented case demonstrates the need to carefully analyze the various symptoms presented by the patient regardless of age. [ABSTRACT FROM AUTHOR]

Introduction and aim. Depressive disorders are a serious mental disorder, the incidence of which is constantly increasing, and thus the socio-economic cost of the disease. Research conducted since the 1960s on depression has not provided either comprehensive information on the mechanisms of the disease or provided highly effective and safe antidepressants. Recent evidence links the dysfunction of the bidirectional communication pathway between the gut microbiome and the central nervous system (known as the microbiota-gut-brain axis) to depressive disorders. Alterations in the composition and function of the intestinal microflora are observed in patients with depression. The aim of this study is to review the current knowledge on the role of the microbiota-gut-brain axis in the pathomechanism of depressive disorders and to discuss potential therapeutic implications. We will explore the use of probiotics, prebiotics, and other nutritional interventions, as well as the development of psychobiotics and other novel pharmacological agents targeting the gut microbiota, for the treatment of depressive disorders. Material and methods. Literature search: A comprehensive literature search was conducted using electronic databases such as PubMed, Embase, and Cochrane Library. The search was conducted using keywords such as "microbiota-gut-brain axis", "depressive disorders", "probiotics", "prebiotics", "psychobiotics" and "pharmacological agents targeting the gut microbiota". Study selection: Studies were included in this review if they investigated the association between the microbiota- gut-brain axis and depressive disorders. Only articles published in English and peer-reviewed were included. Data extraction: Data were extracted from the included studies, including study design, sample size, age range of participants, diagnostic criteria for depressive disorders, methods for assessing gut microbiota, and results. Analysis of literature. The results of the studies were analyzed and synthesized to provide an overview of the current knowledge on the role of the microbiota-gut-brain axis in the pathomechanism of depressive disorders. Results. The findings of the studies were discussed in the context of potential therapeutic implications. The use of probiotics, prebiotics, and other nutritional interventions, as well as the development of psychobiotics and other novel pharmacological agents targeting the gut microbiota, were explored for the treatment of depressive disorders Conclusion. The war negatively changed lifestyle of Ukrainian student via forced relocation and disability to continue education in universities. Among students were detected severe and extremely severe depression, low level of QL due to changes in mental health during war in Ukraine. [ABSTRACT FROM AUTHOR]

Introduction and aim. Sleep is a functional state of the CNS, which appears cyclically in the circadian rhythm. The amount and quality of sleep has a strong impact on mental health, cognitive function (like learning or concentration) and libido. This study aims to show what is the knowledge about the importance of sleep among young people and the impact of sleep deprivation on various aspects of their lives. What's more, we want to show how to improve sleep quality. Material and methods. A literature review was performed by analyzing randomized controlled trials and systematic reviews from PubMed/MEDLINE published in the last five years. For the literature search, following keywords: Sleep quality*, mental health* and libido* were used. Regardless of this, the authors conducted a survey (23 questions) in 555 people (including 404 women and 151 men) aged 15-30. Analysis of literature. Literature review has shown decreased amount of sleep leads to increase susceptibility to irritability, lowered mood, cognitive functions and libido. Also 88% of our respondents noticed an increase in irritability with reduced sleep. Respondents rated their mood higher on days when they slept more, 44% of respondents indicated a decrease in libido with a reduced amount of sleep (34% of people had no opinion). Survey research also shown that 99% of respondents believe that sleep has a significant impact on health. Conclusion. Sleep has a significant impact on various aspects of life. The awareness of young people about the importance of sleep is at a high level, however, this knowledge is not always practical. Therefore, young people should be made aware of the importance of sleep hygiene. [ABSTRACT FROM AUTHOR]

Intra-operative ultrasound has become a relevant imaging modality in neurosurgical procedures. While B-mode, with its intrinsic limitations, is still considered the primary ultrasound modality, intra-operative contrast-enhanced ultrasound (ioCEUS) has more recently emerged as a powerful tool in neurosurgery. Though still not used on a large scale, ioCEUS has proven its utility in defining tumor boundaries, identifying lesion vascular supply and mapping neurovascular architecture. Here we propose a step-by-step procedure for performing ioCEUS analysis of the brain, highlighting its neurosurgical applications. Moreover, we provide practical advice on the use of ultrasound contrast agents and review technical ultrasound parameters influencing ioCEUS imaging. [ABSTRACT FROM AUTHOR]

According to the World Health Organization (WHO), foods high in tryptamine may cause foodborne diseases and abnormal activity in the central nervous system (CNS). The real-time monitoring of tryptamine levels is an emphasized topic among scientific community. In the present work, we report a cost-effective fluorescent paper strips-based methodology impregnated with self-assembled dipeptide-modified (DM1) zinc oxide (ZnO) i.e. DM1@ZnO for the real-time monitoring of tryptamine levels. It is based on an organic-inorganic nanohybrid material of self-assembled N -functionalised dipeptide molecule coated over the surface of ZnO thus tailoring its properties for the detection of tryptamine employing spectroscopic and electrochemical methods. The designed material exhibited a noteworthy response towards tryptamine irrespective of the presence of other biogenic amines (BAs). It selectively displayed blue fluorescence under the 365 nm UV light. On top of that, the detection of tryptamine was also corroborated by its transition to 2-oxytryptamine, as deduced from its electrochemical route. Thus, the proposed paper strip-based methodology unbolts a realistic platform for the efficient recognition of varying levels of tryptamine thus tackling the prima facie reasons for foodborne diseases. [Display omitted] • Fabrication of self-assembled dipeptide-based nanohybrid material. • Spectroscopic and electrochemical recognition of tryptamine. • Interaction of DM1@ZnO with tryptamine and its electrochemical conversion to 2-oxytryptamine. • Fabrication of DM1@ZnO grafted fluorescent paper strips. • Realistic platform for the efficient recognition of tryptamine thus tackling the prima facie reasons for foodborne diseases. [ABSTRACT FROM AUTHOR]

Nasal administration is a non-invasive method of drug delivery that offers several advantages, including rapid onset of action, ease of use, no first-pass effect, and fewer side effects. On this basis, nose-to-brain delivery technology offers a new method for drug delivery to the brain and central nervous system, which has attracted widespread attention. In this paper, the development status and trends of nasal drug delivery and nose-to-brain delivery technology are deeply analyzed through multiple dimensions: literature research, questionnaire surveys, and patent analysis. First, FDA-approved nasal formulations for nose-to-brain delivery were combed. Second, we collected a large amount of relevant information about nasal drug delivery through a questionnaire survey of 165 pharmaceutical industry practitioners in 28 provinces and 161 different organizations in China. Third, and most importantly, we conducted a patent analysis of approximately 700+ patents related to nose-to-brain delivery, both domestically and internationally. This analysis was conducted in terms of patent application trends, technology life cycle, technology composition, and technology evolution. The LDA topic model was employed to identify technological topics in each time window (1990–2023), and the five key major evolution paths were extracted. The research results in this paper will provide useful references for relevant researchers and enterprises in the pharmaceutical industry, promoting the further development and application of nasal drug delivery and nose-to-brain delivery technology. [ABSTRACT FROM AUTHOR]

Background: Walking impairment is one of the most reported symptoms of Multiple Sclerosis (MS). The documentation of gait impairments is important for indexing disease progression and rehabilitation in MS. By measuring and comparing relevant parameters based on the Center of Pressure (COP) patterns, this study aimed to characterize the execution of the gait task and to identify the relationship between these parameters and the level of Expanded Disability Status Scale (EDSS). Methods: Ten women with MS, with an average EDSS score of 2.4, and 10 healthy women were tested using a force plate and motion capture system during the transition from standing to gait posture. The time series of COP were acquired and processed to extract the trajectory-related parameters followed by the COP. Results: The correlation analysis underlined that the progressive alteration of the task execution is directly related to the increase in the EDSS score. These findings suggest that most of the impairments found in people with MS originate from the first part of the COP pattern: the anticipatory postural adjustments (APAs). Before every voluntary movement, the central nervous system performs APAs to minimize the balance perturbation due to the movement itself. Conclusion: Gait initiation APAs play a role in some contractions of ankle muscles and induce a backward COP shift to the swing limb. Our analysis highlighted that patients who affected by MS have a reduced posterior COP shift that reveals the impairment of the anticipatory mechanism. [ABSTRACT FROM AUTHOR]

Introduction and aim. Primary central nervous system lymphoma is a rare, clinically aggressive tumour of the lymphatic system localising 80-90% to the cerebral hemispheres. The rest are located in the spinal cord, cranial nerves or eyeballs. More than 90% of PCNSL cases originate from B lymphocytes. The incidence of the tumour has increased and it develops not only in immunocompromised, but also in immunocompetent individuals. Description of the case. A 47-year-old female patient presented to the Department of Neurology with sudden speech, behaviour and orientation disturbances preceded by severe headaches. The investigations performed indicated a multifocal brain injury of unknown aetiology, most likely inflammatory. After one month, the patient's condition deteriorated despite treatment and she was readmitted to the neurology department. Brain MRI and spectroscopy performed at the beginning of her hospitalisation revealed progression of previous lesions, however, the perfusion result did not indicate a neoplastic process. The investigations suggested acute haemorrhagic encephalomyelitis. Overnight, the woman's neurological condition worsened and there was a significant progression of poor general condition - inertia and increased muscle tone in the left limbs were demonstrated and the patient needed oxygen therapy and catheterisation. 2 weeks after the start of hospitalisation, lesions present on MRI raised the suspicion of lymphoma/glioma. A biopsy was recommended, which revealed PCNSL, an intravascular large B-cell lymphoma. Conclusion. Primary CNS lymphoma is associated with a poor prognosis. Its correct diagnosis is associated with major diagnostic problems and therapeutic difficulties. The course of PCNSL is usually aggressive and the results of treatment are unsatisfactory. [ABSTRACT FROM AUTHOR]

Animex was used to observe the inactive state, regarded to be similar to a sleep state, in socially isolated mice, which were placed in measuring cages just before the onset of a light period. A decreased inactive time in the first 3 h was more observed in these mice compared with mice that were housed in a group. This result suggests that socially isolated mice were more affected by the stimulus of environmental changes, and that the hyperactivity in their central nervous system may be associated with the decrease of their inactive state. [ABSTRACT FROM AUTHOR]

The article focuses on the study of neurovascular syndromes. It mentions that pulsatile propulsion of blood through blood vessels help in the circulation and transport of oxygen and nutrients. It mentions that pulsatile impulse by the heart in the cardiac cycle improves the pressure-related events to capillaries.

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Therapeutic outcomes of local biomolecule delivery to the central nervous system (CNS) using bulk biomaterials are limited by inadequate drug loading, neuropil disruption, and severe foreign body responses. Effective CNS delivery requires addressing these issues and developing well-tolerated, highly-loaded carriers that are dispersible within local neural parenchyma. Here, we synthesized biodegradable trehalose-based polyelectrolyte oligomers using facile A2:B3:AR thiol-ene Michael addition reactions that form complex coacervates upon mixing of oppositely charged oligomers. Coacervates permit high concentration loading and controlled release of bioactive growth factors, enzymes, and antibodies, with modular formulation parameters that confer tunable release kinetics. Coacervates are cytocompatible with cultured neural cells in vitro and can be formulated to either direct intracellular protein delivery or sequester media containing proteins and remain extracellular. Coacervates serve as effective vehicles for precisely delivering biomolecules, including bioactive neurotrophins, to the mouse striatum following intraparenchymal injection. These results support the use of trehalose-based coacervates as part of therapeutic protein delivery strategies for CNS disorders., Competing Interests: Declaration of competing interest Timothy O’Shea reports financial support was provided by Wings for Life Spinal Cord Research Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

A Disintegrin And Metalloprotease 10 (ADAM10), is able to control several important physiopathological processes through the shedding of a large number of protein substrates. Although ADAM10 plays a crucial role in the central nervous system (CNS) development and function, its protein distribution in the CNS has not been fully addressed. Here, we described the regional and cellular ADAM10 protein expression in C57BL/6 mice examined by immunofluorescence 1) throughout the adult mouse brain, cerebellum and spinal cord in vivo and 2) in different cell types as neurons, astrocytes, oligodendrocytes and microglia in vitro. We observed ADAM10 expression through the whole CNS, with a strong expression in the hippocampus, in the hypothalamus and in the cerebral and piriform cortex in the brain, in the Purkinje and in granular cell layers in the cerebellum and in the spinal cord to a lower extent. In vivo, ADAM10 protein expression was mainly found in neurons and in some oligodendroglial cell populations. However, in primary cultures we observed ADAM10 expression in neurons, oligodendrocytes, astrocytes and microglia. Interestingly, ADAM10 was not only found in the membrane but also in cytoplasmic vesicles and in the nucleus of primary cultured cells. Overall, this work highlights a wide distribution of ADAM10 throughout the CNS. The nuclear localization of ADAM10, probably due to its intracellular domain, emphasizes its role in cell signalling in physiological and pathological conditions. Further investigations are required to better elucidate the role of ADAM10 in glial cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

BACKGROUND:: An increasing number of clinical observations suggest adverse neurologic outcome after methylene blue (MB) infusion in the setting of parathyroid surgery. Hence, the aim of the current study was to investigate the potentially neurotoxic effects of MB using a combination of in vivo and in vitro experimental approaches. METHODS:: Isoflurane-anesthetized adult rats were used to evaluate the impact of a single bolus intravascular administration of MB on systemic hemodynamic responses and on the minimum alveolar concentration (MAC) of isoflurane using the tail clamp test. In vivo, MB-induced cell death was evaluated 24 h after MB administration using Fluoro-Jade B staining and activated caspase-3 immunohistochemistry. In vitro, neurotoxic effects of MB were examined in hippocampal slice cultures by measuring excitatory field potentials as well as propidium iodide incorporation after MB exposure. The impact of MB on dendritic arbor was evaluated in differentiated single cell neuronal cultures. RESULTS:: Bolus injections of MB significantly reduced isoflurane MAC and initiated widespread neuronal apoptosis. Electrophysiologic recordings in hippocampal slices revealed a rapid suppression of evoked excitatory field potentials by MB, and this was associated with a dose-dependent effect of this drug on cell death. Dose–response experiments in single cell neuronal cultures revealed that a 2-h-long exposure to MB at non–cell-death-inducing concentrations could still induce significant retraction of dendritic arbor. CONCLUSIONS:: These results suggest that MB exerts neurotoxic effects on the central nervous system and raise questions regarding the safety of using this drug at high doses during parathyroid gland surgery. [ABSTRACT FROM AUTHOR]

Abstract: It is well known that the perinatal developing brain is vulnerable to environmental chemicals such as bisphenol A (BPA). Recent studies have focused on the low dose effects of BPA on the central nervous system (CNS). Sexual dimorphism in the rat''s brain and behaviors, such as locus coeruleus (LC) and open-field behaviors, were sensitively altered by BPA in a sex-dependent manner. This chemical also enhanced the depressive response. It suggests that the developing brain, including the noradrenergic LC cell, is highly sensitive to environmental chemicals, which induces diverse behavioral alterations. [Copyright &y& Elsevier]

The choroid plexus (CP) plays central roles in regulating the microenvironment of the central nervous system by secreting the majority of cerebrospinal fluid (CSF) and controlling its composition. A monolayer of epithelial cells of CP plays a significant role in forming the blood–CSF barrier to restrict the movement of substances between the blood and ventricles. CP epithelial cells are equipped with transporters for glucose and lactate that are used as energy sources. There are many review papers on glucose transporters in CP epithelial cells. On the other hand, distribution of monocarboxylate transporters (MCTs) in CP epithelial cells has received less attention compared with glucose transporters. Some MCTs are known to transport lactate, pyruvate, and ketone bodies, whereas others transport thyroid hormones. Since CP epithelial cells have significant carrier functions as well as the barrier function, a decline in the expression and function of these transporters leads to a poor supply of thyroid hormones as well as lactate and can contribute to the process of age-associated brain impairment and pathophysiology of neurodegenerative diseases. In this review paper, recent findings regarding the distribution and significance of MCTs in the brain, especially in CP epithelial cells, are summarized. [ABSTRACT FROM AUTHOR]

Simple Summary: Diagnosing glioblastoma multiforme (GBM), solitary brain metastases (SBM), and primary central nervous system lymphoma (PCNSL) in malignant tumors of the central nervous system using multi-modal magnetic resonance imaging (MRI) is significantly important in helping physicians develop treatment plans and enhance patient prognosis. In this paper, MFFC-Net is developed and validated using deep learning methods to predict these three tumor categories from multi-modal MRI without the manual region of interest (ROI). MFFC-Net first uses a multi-encoder with DenseBlocks to extract deep features from multi-modal MRI. Then, the feature fusion layer fuses the deep information between different modalities and tissues. Finally, the spatial-channel attention module suppresses redundant new information and activates tumor classification-related features. Compared with radiomics models, MFFC-Net demonstrated higher accuracy. In addition, the results in the different sequences provide important references for future clinical work on MRI image acquisition. We believe that MFFC-Net has the potential to assist in the diagnosis and treatment of brain tumors in the future. (1) Background: Diagnosis of glioblastoma (GBM), solitary brain metastases (SBM), and primary central nervous system lymphoma (PCNSL) plays a decisive role in the development of personalized treatment plans. Constructing a deep learning classification network to diagnose GBM, SBM, and PCNSL with multi-modal MRI is important and necessary. (2) Subjects: GBM, SBM, and PCNSL were confirmed by histopathology with the multi-modal MRI examination (study from 1225 subjects, average age 53 years, 671 males), 3.0 T T2 fluid-attenuated inversion recovery (T2-Flair), and Contrast-enhanced T1-weighted imaging (CE-T1WI). (3) Methods: This paper introduces MFFC-Net, a classification model based on the fusion of multi-modal MRIs, for the classification of GBM, SBM, and PCNSL. The network architecture consists of parallel encoders using DenseBlocks to extract features from different modalities of MRI images. Subsequently, an L 1 − n o r m feature fusion module is applied to enhance the interrelationships among tumor tissues. Then, a spatial-channel self-attention weighting operation is performed after the feature fusion. Finally, the classification results are obtained using the full convolutional layer (FC) and Soft-max. (4) Results: The ACC of MFFC-Net based on feature fusion was 0.920, better than the radiomics model (ACC of 0.829). There was no significant difference in the ACC compared to the expert radiologist (0.920 vs. 0.924, p = 0.774). (5) Conclusions: Our MFFC-Net model could distinguish GBM, SBM, and PCNSL preoperatively based on multi-modal MRI, with a higher performance than the radiomics model and was comparable to radiologists. [ABSTRACT FROM AUTHOR]