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Nerve cells like neurons and astrocytes in central nervous system (CNS) take part in the signaling process which means the transformation of the information from one cell to another via signals. The signaling process is affected by various external parameters like buffers calcium-binding proteins, voltage-gated calcium channel. In the present paper, the role of buffers in the cytoplasmic calcium concentration distribution is shown. The elicitation in calcium concentration is due to the presence of lower amount calcium-binding proteins which can be shown graphically. The mathematical model is designed by keeping in mind the physiological condition taking place in CNS of mammalian brain. The thing to be noted here is that the more elicitation in the calcium concentration distribution results in the cell death which finally give neurodegenerative disease to the mammalian brain. The present paper gives a glimpse of Parkinson’s diseases in particular. Computational results are performed in Wolfram Mathematica 9.0 and simulated on core(TM) i5-3210M CPU @ 2.50 GHz processing speed and 4 GB memory. It is found that the different types of buffer like ethylene glycol-bis(β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid, 1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid and calmodulin have noteworthy effect at different fractions of time. [ABSTRACT FROM AUTHOR]

The motor system relies on the recruitment of motor modules to perform various movements. Muscle synergies are the modules used by the central nervous system to simplify the control of complex motor tasks. In this paper, we aim to explore the primitive synergies to reflect different modes of coordination in upper limb motions. Muscle synergies and corresponding activation coefficients were extracted via non-negative matrix factorization from the electromyography signals of three basic and four complex upper limb motions in sagittal plane and coronal plane. Similarities of muscle synergies and activation coefficients between different tasks and different subjects were compared. Moreover, we used network theory to assess the coordination between multiple muscles and to elucidate the neural implementation of muscle synergies. The results showed that the combination of different sets of primitive muscle synergies can achieve complex motions in different planes. The muscle synergy network topology differed significantly between different tasks. We also demonstrated the potential of this study for the understanding of human motor control mechanism and implications for neurorehabilitation. [ABSTRACT FROM AUTHOR]

The concern about aluminum (Al) toxicity has been proven in various cases. Some cases are associated with the fact that Al is a neurotoxic substance that has been found in high levels in the brain tissues of Alzheimer's disease (AD), epilepsy, and autism patients. Other cases are related to infants, especially premature infants and ones with renal failure, who are at the risk of developing the central nervous system (CNS) and bone toxicity. This risk is a result of infants' exposure to Al from milk formulas, intravenous-feeding solutions, and possibly from aluminum-containing vaccinations. Furthermore, most antiperspirants contain aluminum compounds that raise human exposure to toxic Al. This review paper is intended to discuss in detail the above concerns associated with aluminum, and hence urges the need for more studies exploring the effects of overexposure to Al and recommending mitigation actions. [ABSTRACT FROM AUTHOR]

Maintaining balance is an essential skill regulated by the central nervous system (CNS) that helps humans to function effectively. Developing a physiologically motivated computational model of a neural controller with good performance is a central component for a large range of potential applications, such as the development of therapeutic and assistive devices, diagnosis of balance disorders, and designing robotic control systems. In this paper, we characterize the biomechanics of postural control system by considering the musculoskeletal dynamics in the sagittal plane, proprioceptive feedback, and a neural controller. The model includes several physiological structures, such as the feedforward and feedback mechanism, sensory noise, and proprioceptive feedback delays. A high-gain observer (HGO)-based feedback linearization controller represents the CNS analog in the modeling paradigm. The HGO gives an estimation of delayed states and the feedback linearization control law generates the feedback torques at joints to execute postural recovery movements. The whole scheme is simulated in MATLAB/Simulink. The simulation results show that our proposed scheme is robust against larger perturbations, sensory noises, feedback delays and retains a strong disturbance rejection and trajectory tracking capability. Overall, these results demonstrate that the nonlinear system dynamics, the feedforward and feedback mechanism, and physiological latencies play a key role in shaping the motor control process. [ABSTRACT FROM AUTHOR]

Background and aims: To investigate the prognostic value of blood neurofilament light chain protein (NfL) levels in the acute phase of coronavirus disease 2019 (COVID-19). Methods: We conducted an individual participant data (IPD) meta-analysis after screening on MEDLINE and Scopus to May 23rd 2022. We included studies with hospitalized adult COVID-19 patients without major COVID-19-associated central nervous system (CNS) manifestations and with a measurement of blood NfL in the acute phase as well as data regarding at least one clinical outcome including intensive care unit (ICU) admission, need of mechanical ventilation (MV) and death. We derived the age-adjusted measures NfL Z scores and conducted mixed-effects modelling to test associations between NfL Z scores and other variables, encompassing clinical outcomes. Summary receiver operating characteristic curves (SROCs) were used to calculate the area under the curve (AUC) for blood NfL. Results: We identified 382 records, of which 7 studies were included with a total of 669 hospitalized COVID-19 cases (mean age 66.2 ± 15.0 years, 68.1% males). Median NfL Z score at admission was elevated compared to the age-corrected reference population (2.37, IQR: 1.13–3.06, referring to 99th percentile in healthy controls). NfL Z scores were significantly associated with disease duration and severity. Higher NfL Z scores were associated with a higher likelihood of ICU admission, need of MV, and death. SROCs revealed AUCs of 0.74, 0.80 and 0.71 for mortality, need of MV and ICU admission, respectively. Conclusions: Blood NfL levels were elevated in the acute phase of COVID-19 patients without major CNS manifestations and associated with clinical severity and poor outcome. The marker might ameliorate the performance of prognostic multivariable algorithms in COVID-19. [ABSTRACT FROM AUTHOR]

Substantial pieces of evidence support the potential of exogenous toxins in disrupting neuroimmune homeostasis. It appears that mycotoxins are one of the noticeable sources of naturally occurring substances dysregulating the immune system, which involves the physiology of many organs, such as the central nervous system (CNS). The induction of inflammatory responses in microglial cells and astrocytes, the CNS resident cells with immunological characteristics, could interrupt the hemostasis upon even with low-level exposure to mycotoxins. The inevitable widespread occurrence of a low level of mycotoxins in foods and feed is likely increasing worldwide, predisposing individuals to potential neuroimmunological dysregulations. This paper reviews the current understanding of mycotoxins' neuro-immunotoxic features under low-dose exposure and the possible ways for detoxification and clearance as a perspective. [ABSTRACT FROM AUTHOR]

The study is devoted to analysis of records of rapid coordinated eye movements—saccades. Saccadic eye movements are performed by a human several thousand times a day and have a standard form. Changes in the movement of the eyes, including saccades, are noted in the case of disorders of the central nervous system, middle ear organs, and after a long space flight. Eye movement testing is used in medical practice for diagnosis and control when treating disorders in functioning of the organs of the inner ear, central nervous system, and strabismus. This paper proposes a method for approximating records of saccades with possible presence of pre- and postsaccadic movements. Numerical parameters describing preand postsaccadic movements and asymmetry of a saccade are suggested. The results of a statistical study of forms of saccades in a normal person are given. The statistical study has shown that the difference in forms of saccades is significant. [ABSTRACT FROM AUTHOR]

Quantitative mass spectrometry (MS)–based approaches have allowed further characterization of medulloblastoma (MB) classification and clinical/biological behavior. By investigating protein expression, as well as the role of post-translational modifications in shaping cellular activity, novel avenues of research will clarify the current subgrouping, providing elements for tumor treatment—new molecular targets and signaling cascades—and introducing serum, urinary, and CSF markers of tumor growth and recurrence. We systematically searched and reviewed original research articles treating MB proteomics on PubMed. Reviews, opinion papers, and abstracts were excluded from the final work. A total of 30 novel articles treating the proteomic characterization of MB were included in our review. Research conducted on tissue samples, cell lines, CSF, and urine, as well as exosome and medullospheres, was considered, to picture a broad view of the different directions MS-based proteomic analysis is moving toward. In this review, we collect, summarize, and interpret the current literature on this topic. Significant progress has been achieved in the last decade in MB characterization, paving the way for further exploration of large biobanks of MB and other tissues that will allow a more systematic understanding of MB functioning and clinical progression. [ABSTRACT FROM AUTHOR]

Numerous papers report on connections between creative work and dementing illness, particularly in frontotemporal dementia (FTD), which may combine with motor neuron disease (FTD-MND). However, the emergence of FTD(-MND) patients' de novo artistic activities is rarely reported and underappreciated. Therefore, the present review summarizes relevant case studies' outcomes, capturing creativity's multifaceted nature. Here, we systematically searched for case reports by paying particular attention to the chronological development of individual patients' clinical symptoms, signs, and life events. We synoptically compared the various art domains to the pattern of brain atrophy, the clinical and pathological FTD subtypes. 22 FTD(-MND) patients were identified with creativity occurring either at the same time (41%) or starting after the disease onset (59%); the median lag between the first manifestation of disease and the beginning of creativity was two years. In another five patients, novel artistic activity was developed by a median of 8 years before the start of dementia symptoms. Artistic activity usually evolved over time with a peak in performance, followed by a decline that was further hampered by physical impairment during disease progression. Early on, the themes and objects depicted were often concrete and realistic, but they could become more abstract or symbolic at later stages. Emergent artistic processes may occur early on in the disease process. They appear to be a communication of inner life and may also reflect an attempt of compensation or "self-healing". The relative preservation of primary neocortical areas such as the visual, auditory, or motor cortex may enable the development of artistic activity in the face of degeneration of association cortical areas and subcortical, deeper central nervous system structures. It is crucial to understand the differential loss of function and an individual's creative abilities to implement caregiver-guided, personalized therapeutic strategies such as art therapy. [ABSTRACT FROM AUTHOR]

Steroid-responsive encephalopathy is a general term for diseases that are characterized by diffuse brain injury and respond well to corticosteroids or immunosuppressive agents, including Hashimoto's encephalopathy (HE), limbic encephalitis (LE), systemic lupus erythematosus encephalopathy (SLEE), antineutrophil cytoplasmic antibodies (ANCA)-associated systemic vasculitis encephalopathy (AASV), viral encephalitis (VE), and primary central nervous system lymphoma (PCNSL). Epilepsy and status epilepticus are the main manifestations of steroid-responsive encephalopathy. The spectrum of "autoimmune epilepsy" diseases, which has been approved by the epilepsy diagnostic recommendations of the International Antiepileptic League, is characterized by a high prevalence of epilepsy in central nervous system (CNS) autoimmune diseases and a variety of neuron-specific autoantibodies. Steroid-responsive encephalopathy with different causes may have different pathogeneses and has been suggested to be associated with some internal commonality producing seizure as the main symptom. Determining the regularity of seizures caused by steroid-responsive encephalopathy and implementing appropriate measures will help us improve the prognosis of patients. This paper summarizes the epidemiology, seizure onset, seizure type, and other characteristics of seizures in steroid-responsive encephalopathy (including HE, LE, SLEE, ANCA-associated systemic vasculitis encephalopathy, VE, and PCNSL) and then discusses the use of antiepileptic drugs to treat steroid-responsive encephalopathy. [ABSTRACT FROM AUTHOR]

The majority of the population in Bangladesh uses traditional plant-based medicines to manage various ailments, including central nervous system (CNS) disorders. This review presents ethnobotanical information and relevant scientific studies on plants used in traditional healthcare for the management of various CNS disorders in Bangladesh. The information on the medicinal plants of Bangladesh effective against CNS disorders published in scientific journals, books, and reports was compiled from different electronic databases using specific key words. The present article provides comprehensive information on a total of 224 medicinal plant species belonging to 81 families used for the treatment of CNS disorders by the various peoples of Bangladesh. In total, we reviewed more than 290 relevant papers. In this study, leaves were found as the most often used plant organ, followed by roots, fruits, whole plants, barks, seeds, stems, rhizomes, and flowers. The Fabaceae family contributes the highest number of used species, followed by Rubiaceae, Lamiaceae, Cucurbitaceae, Vitaceae, Euphorbiaceae, Malvaceae, and Zingiberaceae. The most frequently used species (in decreasing order) are Asparagus racemosus, Centella asiatica, Stephania japonica, Aegle marmelos, Coccinia grandis, Tabernaemontana divaricata, Bacopa monnieri, Abroma augusta, and Scoparia dulcis. This review may serve as a starting point for a rational search for neuroactive natural products against CNS disorders within the Flora of Bangladesh. [ABSTRACT FROM AUTHOR]

Fetal ventriculomegaly is the most common central nervous system abnormality detected by prenatal imaging. It has a high association with other anomalies. Etiologies and prognoses for fetal ventriculomegaly range from normal outcomes to significant neurodevelopmental sequelae. In this paper, we review the development, terminology, pathogenesis, imaging and prognosis of fetal ventriculomegaly. [ABSTRACT FROM AUTHOR]

Objectives: To perform a systematic review regarding the developments in the field of radiomics in lymphoma. To evaluate the quality of included articles by the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2), the phases classification criteria for image mining studies, and the radiomics quality scoring (RQS) tool. Methods: We searched for eligible articles in the MEDLINE/PubMed and EMBASE databases using the terms "radiomics", "texture" and "lymphoma". The included studies were divided into two categories: diagnosis-, therapy response- and outcome-related studies. The diagnosis-related studies were evaluated using the QUADAS-2; all studies were evaluated using the phases classification criteria for image mining studies and the RQS tool by two reviewers. Results: Forty-five studies were included; thirteen papers (28.9%) focused on the differential diagnosis of primary central nervous system lymphoma (PCNSL) and glioblastoma (GBM). Thirty-two (71.1%) studies were classified as discovery science according to the phase classification criteria for image mining studies. The mean RQS score of all studies was 14.2% (ranging from 0.0 to 40.3%), and 23 studies (51.1%) were given a score of < 10%. Conclusion: The radiomics features could serve as diagnostic and prognostic indicators in lymphoma. However, the current conclusions should be interpreted with caution due to the suboptimal quality of the studies. In order to introduce radiomics into lymphoma clinical settings, the lesion segmentation and selection, the influence of the pathological pattern and the extraction of multiple modalities and multiple time points features need to be further studied. Key Points: • The radiomics approach may provide useful information for diagnosis, prediction of the therapy response, and outcome of lymphoma. • The quality of published radiomics studies in lymphoma has been suboptimal to date. • More studies are needed to examine lesion selection and segmentation, the influence of pathological patterns, and the extraction of multiple modalities and multiple time point features. [ABSTRACT FROM AUTHOR]

This paper reviews recent developments in the still-off-the-mainstream information and data processing area of spiking neural networks (SNN)—the third generation of artificial neural networks. We provide background information about the functioning of biological neurons, discussing the most important and commonly used mathematical neural models. Most relevant information processing techniques, learning algorithms, and applications of spiking neurons are described and discussed, focusing on feasibility and biological plausibility of the methods. Specifically, we describe in detail the functioning and organization of the latest version of a 3D spatio-temporal SNN-based data machine framework called NeuCube, as well as it's SNN-related submodules. All described submodules are accompanied with formal algorithmic formulations. The architecture is highly relevant for the analysis and interpretation of various types of spatio-temporal brain data (STBD), like EEG, NIRS, fMRI, but we highlight some of the recent both STBD- and non-STBD-based applications. Finally, we summarise and discuss some open research problems that can be addressed in the future. These include, but are not limited to: application in the area of EEG-based BCI through transfer learning; application in the area of affective computing through the extension of the NeuCube framework which would allow for a biologically plausible SNN-based integration of central and peripheral nervous system measures. Matlab implementation of the NeuCube's SNN-related module is available for research and teaching purposes. [ABSTRACT FROM AUTHOR]

Introduction: Spasticity is the result of an exaggeration of the monosynaptic muscle stretch reflex due to lesions affecting the central nervous system, in particular an upper motor neuron lesion. Selective dorsal rhizotomy (SDR) is a surgical technique developed to treat spastic diplegia, one of the common forms of cerebral palsy, resulting from the lack of supraspinal inhibitory controls. The aim of SDR is to identify and cut a critical amount of the sensory rootlets, in particular those contributing the most to spasticity, in order to relieve the patient from lower limb spasticity while preserving motor strength and sphincter control. Various surgical techniques to perform SDR have been proposed over time. Similarly, intraoperative neurophysiology (ION)—first introduced by Fasano and colleagues in 1976—is a safe and effective tool to guide the surgeon in the procedure of SDR, but different ION strategies are used by different authors, and the value of ION itself has been questioned. Methods: The purpose of this paper is to review the anatomo-physiological background of SDR, the historical development of the surgical technique, and the essential principles of ION. Results: While some surgeons privilege a single-level approach and others a multi-level approach, nowadays, there are still neither agreement nor guidelines on the percentage of roots to be cut. Rather, a tailored approach based on both the preoperative functional status as well as intraoperative ION findings seems reasonable. ION is considered not essential to decide the percentage of roots to cut, but it assists to distinguish between ventral and dorsal roots, and to preserve sphincterial function, whenever S2 rootlets are included in SDR. Conclusions: To optimize the balance between reduction of spasticity and preservation of motor strength while minimizing the neurological damage remains the main goal of SDR. [ABSTRACT FROM AUTHOR]

Background: Seemingly, the Matrix metalloproteinases (MMPs) play a role in the etiopathogenesis of coronavirus disease 2019 (COVID-19). Here in this study, we determined the association of MMP9 rs3918242, MMP3 rs3025058, and MMP2 rs243865 polymorphisms with the risk of COVID-19, especially in those with neurological syndrome (NS). Methods: We enrolled 500 patients with COVID-19 and 500 healthy individuals. To genotype the target SNPs, the Real-time allelic discrimination technique was used. To determine serum levels of MMPs, Enzyme-linked immunosorbent assay (ELISA) was exerted. Results: The MMP9 gene rs3918242 and MMP3 gene rs3025058 SNP were significantly associated with increased COVID-19 risk and susceptibility to COVID-19 with NS. The serum level of MMP-9 and MMP-3 was significantly higher in COVID-19 cases compared with the healthy controls. Serum MMP-9 and MMP-3 levels were also higher in COVID-19 subjects with NS in comparison to the healthy controls. The polymorphisms in MMP genes were not associated with serum level of MMPs. Conclusion: MMP9 and MMP3 gene polymorphisms increases the susceptibility to COVID-19 as well as COVID-19 with neurologic syndrome, but they probably have no role in the regulation of serum MMP-9 and MMP-3 levels. [ABSTRACT FROM AUTHOR]

Albert Feng pioneered the study of neuroethology of sound localization in anurans by combining behavioral experiments on phonotaxis with detailed investigations of neural processing of sound direction from the periphery to the central nervous system. The main advantage of these studies is that many species of female frogs readily perform phonotaxis towards loudspeakers emitting the species-specific advertisement call. Behavioral studies using synthetic calls can identify which parameters are important for phonotaxis and also quantify localization accuracy. Feng was the first to investigate binaural processing using single-unit recordings in the first two auditory nuclei in the central auditory pathway and later investigated the directional properties of auditory nerve fibers with free-field stimulation. These studies showed not only that the frog ear is inherently directional by virtue of acoustical coupling or crosstalk between the two eardrums, but also confirmed that there are extratympanic pathways that affect directionality in the low-frequency region of the frog's hearing range. Feng's recordings in the midbrain also showed that directional information is enhanced by cross-midline inhibition. An important contribution toward the end of his career involved his participation in neuroethological research with a team of scientists working with frogs that produce ultrasonic calls. [ABSTRACT FROM AUTHOR]

In this article the author comments on the review papers published within the issue which show that mutation in human GRN gene was the cause of frontotemporal lobar dementia (FTLD). As stated, very little was known about the importance of progranulin, a protein that regulates cell division, survival and migration within the central nervous system. He opines that the prevailing hypothesis of global GRN haploinsufficiency is too simple to account for development of FTLD.

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

In this paper, we outline some important milestones in the history of the term “plasticity” in reference to the nervous system. Credit is given to William James for first adopting the term to denote changes in nervous paths associated with the establishment of habits; to Eugenio Tanzi for first identifying the articulations between neurons, not yet called synapses, as possible sites of neural plasticity; to Ernesto Lugaro for first linking neural plasticity with synaptic plasticity; and to Cajal for complementing Tanzi’s hypothesis with his own hypothesis of plasticity as the result of the formation of new connections between cortical neurons. Cajal’s early use of the word plasticity is demonstrated, and his subsequent avoidance of the term is tentatively accounted for by the fact that other authors extended it to mean neuronal reactions partly pathological and no doubt quite different from those putatively associated with normal learning. Evidence is furnished that in the first two decades of the twentieth century the theory was generally accepted that learning is based on a reduced resistance at exercized synapses, and that neural processes become associated by coactivation. Subsequently the theory fell in disgrace when Lashley’s ideas about mass action and functional equipotentiality of the cortex tended to outmode models of the brain based on orthodox neural circuitry. The synaptic plasticity theory of learning was rehabilitated in the late 1940s when Konorski and particularly Hebb argued successfully that there was no better alternative way to think about the modifiability of the brain by experience and practice. Hebb’s influential hypothesis about the mechanism of adult learning contained elements strikingly similar to the early speculations of James, Tanzi and Cajal, but Hebb did not acknowledge specifically these roots of his thinking about the brain, though he was fully aware that he had resurrected old ideas wrongly neglected for a long time. Lately the concept of neural plasticity has been complicated by attributing considerably different meanings to it. A scholarly paper by Paillard is used to show how an analysis in depth can clarify some confusion engendered by an unrestricted use of the concept and term of neural plasticity. [ABSTRACT FROM AUTHOR]

Neurons are regarded as basic, structural and functional units of the central nervous system. They play an active role in the collection, storing and transferring of the information during signal processing in the brain. In this paper, we investigate the dynamics of a model of a 4D autonomous Hopfield neural network (HNN). Our analyses highlight complex phenomena such as chaotic oscillations, periodic windows, hysteretic dynamics, the coexistence of bifurcations and bursting oscillations. More importantly, it has been found several sets of synaptic weight for which the proposed HNN displays multiple coexisting stable states including three disconnected attractors. Besides the phenomenon of coexistence of attractors, the bursting phenomenon characterized by homoclinic/Hopf cycle–cycle bursting via homoclinic/fold hysteresis loop is observed. This contribution represents the first case where the later phenomenon (bursting oscillations) occurs in an autonomous HNN. Also, PSpice simulations are used to support the results of the previous analyses. [ABSTRACT FROM AUTHOR]

The pervasive and devastating nature of substance use disorders underlies the need for the continued development of novel pharmacotherapies. We now know that glia play a much greater role in neuronal processes than once believed.  The various types of glial cells (e.g., astrocytes, microglial, oligodendrocytes) participate in numerous functions that are crucial to healthy central nervous system function. Drugs of abuse have been shown to interact with glia in ways that directly contribute to the pharmacodynamic effects responsible for their abuse potential. Through their effect upon glia, drugs of abuse also alter brain function resulting in behavioral changes associated with substance use disorders. Therefore, drug-induced changes in glia and inflammation within the central nervous system (neuroinflammation) have been investigated to treat various aspects of drug abuse and dependence. This article presents a brief overview of the effects of each of the major classes of addictive drugs on glia. Next, the paper reviews the pre-clinical and clinical studies assessing the effects that glial modulators have on abuse-related behavioral effects, such as pleasure, withdrawal, and motivation. There is a strong body of pre-clinical literature demonstrating the general effectiveness of several glia-modulating drugs in models of reward and relapse. Clinical studies have also yielded promising results, though not as robust. There is still much to disentangle regarding the integration between addictive drugs and glial cells. Improved understanding of the relationship between glia and the pathophysiology of drug abuse should allow for more precise exploration in the development and testing of glial-directed treatments for substance use disorders. [ABSTRACT FROM AUTHOR]

One of the most important evolutionary innovations of vertebrates is a complexly structured telencephalon, which provides higher forms of nervous activity in animals and humans. This work is devoted to the study of the appearance of the telencephalon in the early stages of vertebrate evolution. At the same time, there is reason to believe that lampreys, due to their evolutionary antiquity, could retain some ancient expression patterns of genes that regulate the development of the brain in the very first vertebrates. The study of the features of spatio-temporal expression patterns of key genes that regulate the development of the forebrain in lampreys compared with other vertebrates can help to understand the molecular mechanisms underlying the appearance and evolutionary development of this unique structure of vertebrates. This paper presents the results from analyzing the gene-expression dynamics of Lanf, FoxG1, Otx2, Goosecoid, and HoxB9 in the early stages of development of the European river lamprey Lampetra fluviatilis. It was shown that lamprey genes involved in telencephalon differentiation (Lanf and FoxG1) exhibit heterochrony of expression compared with more evolutionarily advanced representatives of vertebrates. This fact confirms the idea that the telencephalon, being evolutionarily the youngest part of the brain, could appear in vertebrate ancestors as a superstructure in the late stages of their embryonic development. [ABSTRACT FROM AUTHOR]

Chronic pain surrounding the temporomandibular joints and masticatory muscles is often the primary chief complaint of patients with temporomandibular disorders (TMD) seeking treatment. Yet, the neuro-pathophysiological basis underlying it remains to be clarified. Neuroimaging techniques have provided a deeper understanding of what happens to brain structure and function in TMD patients with chronic pain. Therefore, we performed a systematic review of magnetic resonance imaging (MRI) studies investigating structural and functional brain alterations in TMD patients to further unravel the neurobiological underpinnings of TMD-related pain. Online databases (PubMed, EMBASE, and Web of Science) were searched up to August 3, 2019, as complemented by a hand search in reference lists. A total of 622 papers were initially identified after duplicates removed and 25 studies met inclusion criteria for this review. Notably, the variations of MRI techniques used and study design among included studies preclude a meta-analysis and we discussed the findings qualitatively according to the specific neural system or network the brain regions were involved in. Brain changes were found in pathways responsible for abnormal pain perception, including the classic trigemino-thalamo-cortical system and the lateral and medial pain systems. Dysfunction and maladaptive changes were also identified in the default mode network, the top-down antinociceptive periaqueductal gray-raphe magnus pathway, as well as the motor system. TMD patients displayed altered brain activations in response to both innocuous and painful stimuli compared with healthy controls. Additionally, evidence indicates that splint therapy can alleviate TMD-related symptoms by inducing functional brain changes. In summary, MRI research provides important novel insights into the altered neural manifestations underlying chronic pain in TMD. [ABSTRACT FROM AUTHOR]

Background Generic drug exchange is common practice in most healthcare systems. While generics certainly contribute to economic savings, the altered drug formulation might be associated with potential therapeutic problems. Given the narrow therapeutic windows in neurologic indications, any detrimental effect on the therapy can lead to significant consequences. Aim of the review This review aims to investigate potential problems related to a switch from brand-name to generic or from generic to generic drug products in patients with neurologic diseases. Method The review was conducted following the PICO framework and the PRISMA guidelines. MEDLINE and Scopus databases were searched for articles published in English and German language between January 1, 1995 and October 17, 2018. Studies included in this review were randomized controlled studies, reviews, systematic reviews, overviews, cohort studies and case-control studies. Studies excluded were letters, comments, authors view, congress or seminar papers and studies with a focus on economic impact or costs. Results were synthesized qualitatively. The primary outcomes were pharmacokinetic parameters such as the area under the curve (AUC), the peak serum concentration (cmax) or the time at which cmax is observed (tmax). Results The search identified 67 studies with a great variety of endpoints and study designs. The leading indication was epilepsy. Two small RCTs were found on lamotrigine switch. Analysis of the other studies found no significant differences in pharmacokinetic parameters when switching to generic drugs. A more heterogeneous picture was revealed regarding hospitalizations, breakthrough seizures, failure of therapy, adherence and patient concerns. Conclusion While most reports were of poor quality, lamotrigine was the drug with the best available data. Summarizing the results of the available studies, pharmacokinetic parameters of antiepileptic drugs show low deviation. In contrast, data on clinical parameters are less consistent. Some studies found increased seizure frequencies and adverse-drug events, while others showed no complications. Adherence and patient satisfaction seemed to be impaired. In daily practice, generic exchange in epilepsy should be a carefully balanced decision, conducted with great caution. Further research is needed, especially regarding neurologic indications other than epilepsy. [ABSTRACT FROM AUTHOR]

The human gut microbiome partakes in a bidirectional communication pathway with the central nervous system (CNS), named the microbiota-gut-brain axis. The microbiota-gut-brain axis is believed to modulate various central processes through the vagus nerve as well as production of microbial metabolites and immune mediators which trigger changes in neurotransmission, neuroinflammation, and behavior. Little is understood about the utilization of microbiome manipulation to treat disease. Though studies exploring the role of the microbiome in various disease processes have shown promise, mechanisms remain unclear and evidence-based treatments for most illnesses have not yet been developed. The animal studies reviewed here offer an excellent array of basic science research that continues to clarify mechanisms by which the microbiome may affect mental health. More evidence is needed, particularly as it relates to translating this work to human subjects. The studies presented in this paper largely demonstrate encouraging results in the treatment of depression. Limitations include small sample sizes and heterogeneous methodology. The exact mechanism by which the gut microbiota causes or alters neuropsychiatric disease states is not fully understood. In this review, we focus on recent studies investigating the relationship between gut microbiome dysbiosis and the pathogenesis of depression. This article is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors. [ABSTRACT FROM AUTHOR]

Spinal cord Magnetic Resonance Images (MRI) have a remarkable role to play in the learning of neurological diseases such as Multiple Sclerosis (MS) affecting the Central Nervous System (CNS), in which spinal cord atrophy can help in the measurement of disease advancement and the changes in shape. Spinal cord segmentation plays a significant part in analyzing the neurological disease. In this paper here, an approach on the basis of the automatic spinal cord segmentation is proposed. This automatic technique presented performs the segmentation of the spinal cord with the help of MRI datasets. This new segmentation follows the interactive Random-Walk solvers (RW) along with Artificial Bee Colony (ABC) optimization algorithm in order to be an entirely automatic flow pipeline. The initialization of the automatic segmentation pipeline is then done with a reliable voxel-wise classification employing features similar to Haar and supervised machine learning technique i.e. Probabilistic Boosting Tree (PBT) along with Support Vector Machine (SVM) so named as PBTSVM. Thereafter, the extraction of the refinement topology of the spinal cord is then done from the temporary segmentation and it is fine-tuned for the further next random-walk solver with ABC. The refined topology results in the spinal cord's boundary conditions from the MRI that permits the following random-walk solver with ABC for improving the segmentation result. The experimental outcomes of the novel segmentation approach depending on the MRI images indicate that the system proposed PBT-SVM algorithm provides better accuracy when compared to the other existing Active Contour Model, Multi-Resolution Propagation algorithms. Experimentation results of the proposed PBT-SVM algorithm produces higher accuracy results of 93% which is 2.5 and 3.233% higher when compared to Active Contour Model and Multi-Resolution Propagation methods respectively. [ABSTRACT FROM AUTHOR]

In this paper, we showed the gold nanoparticles (Au NPs) synthesis using the aqueous leaf extract of Mansoa alliacea. The biofabricated Au NPs were studied using X-ray diffractometer (XRD), UV–Vis spectroscopy, transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy, and energy dispersive X-ray analysis. XRD results confirmed the crystalline nature of Au NPs with face centered cubic structure. TEM images confirmed that the particles are in the range of 20–30 nm. Further, the prepared Au NPs effects were determined by the tail-flick examination, a sensitive drugs model which acts at central nervous system. The thermal threshold's maximum increase was noticed to be 3.6 times to that of vehicle treated at 2 h after treatments. Au NPs were even capable to inverse the complete Freund's adjuvant induced thermal hyperalgesia, which is same as detected under physiological situations. [ABSTRACT FROM AUTHOR]

Background and aims: Metronidazole, a commonly used antibiotic drug, can cause adverse effects in the central nervous system termed metronidazole-induced encephalopathy, leading to diagnostic challenges. The condition is rare and a detailed description of its phenotype is lacking. In this systematic review we investigated the clinical features of metronidazole-induced encephalopathy to promote recognition and elaborate the description. Methods: We performed a systematic literature search using PubMed.gov and hand searched the reference lists of included articles and other publications of interest. We included case series and single reports describing individual patients developing symptoms from the central nervous system in relation to metronidazole treatment. Data were extracted and analyzed descriptively. Results: We identified 779 publications of which 112 papers comprising 136 patients were included. Typical findings were dysarthria, gait instability, limb dyscoordination and altered mental status. Frequently, patients concomitantly presented with metronidazole-induced polyneuropathy. Liver disease was the most common pre-existing condition. MRI showed a characteristic pattern of reversible symmetrical hyperintense lesions on T2/FLAIR of the dentate nuclei in 90% of patients. Most patients improved significantly after discontinuation of metronidazole. Poor outcome was associated with severe comorbidity. Conclusion: Metronidazole-induced encephalopathy should be considered in patients presenting with neurological symptoms in relation to newly initiated or prolonged metronidazole treatment. MRI changes are highly characteristic and specific. Patients with liver disease are at increased risk. Prognosis is good if recognized early. [ABSTRACT FROM AUTHOR]

Introduction: Neurodegeneration is the term describing the death of neurons both in the central nervous system and periphery. When affecting the central nervous system, it is responsible for diseases like Alzheimer's disease, Parkinson's disease, Huntington's disorders, amyotrophic lateral sclerosis, and other less frequent pathologies. There are several common pathophysiological elements that are shared in the neurodegenerative diseases. The common denominators are oxidative stress (OS) and inflammatory responses. Unluckily, these conditions are difficult to treat. Because of the burden caused by the progression of these diseases and the simultaneous lack of efficacious treatment, therapeutic approaches that could target the interception of development of the neurodegeneration are being widely investigated. This review aims to highlight the most recent proposed novelties, as most of the previous approaches have failed. Therefore, older approaches may currently be used by healthcare professionals and are not being presented.Methods: This review was based on an electronic search of existing literature, using PubMed as primary source for important review articles, and important randomized clinical trials, published in the last 5 years. Reference lists from the most recent reviews, as well as additional sources of primary literature and references cited by relevant articles, were used.Results: Eighteen natural pharmaceutical substances and 24 extracted or recombinant products, and artificial agents that can be used against OS, inflammation, and neurodegeneration were identified. After presenting the most common neurodegenerative diseases and mentioning some of the basic mechanisms that lead to neuronal loss, this paper presents up to date information that could encourage the development of better therapeutic strategies.Conclusions: This review shares the new potential pharmaceutical and not pharmaceutical options that have been recently introduced regarding OS and inflammatory responses in neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Multiple Sclerosis (MS) is a chronic inflammatory disease causing demyelination and neurodegeneration in the central nervous system (CNS). Although the exact etiology of MS is still unclear, both genetic and environmental elements are regarded as causative factors. Environmental factors can induce a cascade of events in immune system leading to neuronal death and nerve demyelination. This paper aims to compare the peripheral transcript levels of Ermin (ERMN) (a gene with putative role in cytoskeletal rearrangements during myelinogenesis) and Listerin E3 Ubiquitin Protein Ligase 1 (LTN1) (a gene with functions in regulating innate immune system) between relapsing-remitting MS (RR-MS) patients and healthy controls. The results showed a significant decrease in ERMN expression (p = 0.022); whereas, no significant difference was detected in LTN1 expression between two groups (p = 0.935). The reduction in ERMN expression in leukocytes could be the cause of demyelinating process in RR-MS patients. Current findings might also have practical importance in prognosis and targeted therapies. [ABSTRACT FROM AUTHOR]

A central objective in deciphering the nervous system in health and disease is to define the connections of neurons. The propensity of neurotropic viruses to spread among synaptically-linked neurons makes them ideal for mapping neural circuits. So far, several classes of viral neuronal tracers have become available and provide a powerful toolbox for delineating neural networks. In this paper, we review the recent developments of neurotropic viral tracers and highlight their unique properties in revealing patterns of neuronal connections. [ABSTRACT FROM AUTHOR]

Recent finding has demonstrated that glial cells and especially astrocytes are responsible for some important roles in the central nervous system. Laboratory examination of the roles of astrocytes in information processing of neural system is associated with technical difficulties. Therefore, computational modeling provides a suitable approach in describing cognitive phenomena and neuroscience. In this paper, the role of strong and weak astrocytes in pattern recognition has considered and bio-stimulator was used to compensate the malfunction of the weak astrocyte. Therefore, we designed the tripartite synapses network, which astrocytes dominate the synaptic spaces. Then, the network has been trained on MNIST dataset. After that, the control feedback of astrocyte to pre- and postsynaptic neurons has decreased so that the astrocyte dominance on synaptic transitions decreased and impaired tripartite synapses network has been configured. In the next step, due to the destructive effects of impaired astrocyte, based on the dynamical model of the astrocyte biophysical model, a bio-inspired stimulator was designed. Accordingly, a new concept "Stimulating the impaired astrocytes to compensate their malfunction in pattern recognition" was introduced. This new mechanism was proposed to stimulate the impaired astrocytes in a population of tripartite synapses for restoration of the normal neural oscillations. Reported results confirmed that the increased error of "always firing" in pattern recognition caused by astrocytes dysfunction could be compensated by the bio-inspired stimulator. [ABSTRACT FROM AUTHOR]

Neurodevelopmental deficits in pediatric and adult survivors of childhood onset chronic kidney disease (CKD) have been documented for many years. This paper reviews the available literature on central nervous system involvement incurred in childhood CKD. The studies reviewed include recent work in neuroimaging, electrophysiology, and neuropsychology, along with commentary on school functioning and long-term outcomes. The paper concludes with suggestions for monitoring the neurodevelopmental status and pursuing appropriate early interventions for children with CKD. [ABSTRACT FROM AUTHOR]

A motor action often involves the coordination of several motor synergies and requires flexible adjustment of the ongoing execution based on feedback signals. To elucidate the neural mechanisms underlying the construction and selection of motor synergies, we study prey-capture in anurans. Experimental data demonstrate the intricate interaction between different motor synergies, including the interplay of their afferent feedback signals (Weerasuriya 1991; Anderson and Nishikawa 1996). Such data provide insights for the general issues concerning two-way information flow between sensory centers, motor circuits and periphery in motor coordination. We show how different afferent feedback signals about the status of the different components of the motor apparatus play a critical role in motor control as well as in learning. This paper, along with its companion paper, extend the model by Liaw et al. (1994) by integrating a number of different motor pattern generators, different types of afferent feedback, as well as the corresponding control structure within an adaptive framework we call Schema-Based Learning. We develop a model of the different MPGs involved in prey-catching as a vehicle to investigate the following questions: What are the characteristic features of the activity of a single muscle? How can these features be controlled by the premotor circuit? What are the strategies employed to generate and synchronize motor synergies? What is the role of afferent feedback in shaping the activity of a MPG? How can several MPGs share the same underlying circuitry and yet give rise to different motor patterns under different input conditions? In the companion paper we also extend the model by incorporating learning components that give rise to more flexible, adaptable and robust behaviors. To show these aspects we incorporate studies on experiments on lesions and the learning processes that allow the animal to recover its proper functioning [ABSTRACT FROM AUTHOR]

What one may see upon microscopic examination of sections of specimens of human and animal tissues is not always related to the normal histology or pathology of the tissue in question. Defects or abnormalities in tissue sections may result from the faulty processing of the tissue specimens. These are referred to as artefacts. Some artefacts are easily distinguished from normal or pathological tissue components, and some are difficult to distinguish from such entities. With the aid of images of tissue sections, this paper will endeavour to illustrate some of the many hundreds of artefacts that are most frequently encountered in the preparation of microscopic tissue sections. Artefacts may occur at different stages in the routine collection of tissues, fixation, processing, cutting and staining of tissues. This paper will cover the artefacts resulting at each stage of the above processes in a sequential manner. In providing reliable information about different artefacts and the stage at which they occurred, it is hoped that techniques will be improved to reduce artefact occurrence in the future. [ABSTRACT FROM AUTHOR]

This paper focuses on the links between Jakob von Uexküll's theoretical biology and Adolf Portmann's conception of organic life. Its main purpose is to show that Uexküll and Portmann not only share a view of the living being as an autonomous and holistically organized entity, but also base this view on the seminal idea of the subjectivity of the organism. In other words, the respective holistic principles securing the autonomy of the living being—the Bauplan, for Uexküll; the Innerlichkeit, for Portmann—share an essentially subjective character. Such principles, indeed, express themselves in a centrally directed and formative way; moreover, in organisms endowed with a central nervous system, they also extend their influence on the overt behavioral sphere and on the organism's capacity to give meaning to the surrounding reality. The conclusion of the article will show how, though starting from this common background, the two authors develop divergent positions on the issue of the anthropological difference. If Portmann emphasizes the special status of the relationship between the human animal and the world, Uexküll tends to see a substantial continuity in the biosemiotic processes through which human and non-human animals constitute their species-specific worlds of experience (Umwelten). [ABSTRACT FROM AUTHOR]

The meninges are critical for the brain functions, but the diversity of meningeal cell types and intercellular interactions have yet to be thoroughly examined. Here we identify a population of meningeal lymphatic supporting cells (mLSCs) in the zebrafish leptomeninges, which are specifically labeled by ependymin. Morphologically, mLSCs form membranous structures that enwrap the majority of leptomeningeal blood vessels and all the mural lymphatic endothelial cells (muLECs). Based on its unique cellular morphologies and transcriptional profile, mLSC is characterized as a unique cell type different from all the currently known meningeal cell types. Because of the formation of supportive structures and production of pro-lymphangiogenic factors, mLSCs not only promote muLEC development and maintain the dispersed distributions of muLECs in the leptomeninges, but also are required for muLEC regeneration after ablation. This study characterizes a newly identified cell type in leptomeninges, mLSC, which is required for muLEC development, maintenance, and regeneration. The meninges are a structure within the central nervous system that protects and provides supportive functions. Here they identify a population of meningeal lymphatic supporting cells within the zebrafish leptomeninges and characterize their roles in supporting mural lymphatic endothelial cell development and homeostasis. [ABSTRACT FROM AUTHOR]

Acute brain slices represent a workhorse model for studying the central nervous system (CNS) from nanoscale events to complex circuits. While slice preparation inherently involves tissue damage, it is unclear how microglia, the main immune cells and damage sensors of the CNS react to this injury and shape neuronal activity ex vivo. To this end, we investigated microglial phenotypes and contribution to network organization and functioning in acute brain slices. We reveal time-dependent microglial phenotype changes influenced by complex extracellular ATP dynamics through P2Y12R and CX3CR1 signalling, which is sustained for hours in ex vivo mouse brain slices. Downregulation of P2Y12R and changes of microglia-neuron interactions occur in line with alterations in the number of excitatory and inhibitory synapses over time. Importantly, functional microglia modulate synapse sprouting, while microglial dysfunction results in markedly impaired ripple activity both ex vivo and in vivo. Collectively, our data suggest that microglia are modulators of complex neuronal networks with important roles to maintain neuronal network integrity and activity. We suggest that slice preparation can be used to model time-dependent changes of microglia-neuron interactions to reveal how microglia shape neuronal circuits in physiological and pathological conditions. Microglia undergo rapid phenotype changes in response to tissue disturbances but the impact of these changes on neuronal networks is unclear. Here, the authors show that microglia contribute to neuronal synchrony in acute brain slices, while their marked phenotypic transformation is influenced by injury-related focal ATP events. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is characterized by heterogeneity in disease course and prediction of long-term outcome remains a major challenge. Here, we investigate five myeloid markers – CHIT1, CHI3L1, sTREM2, GPNMB and CCL18 – in the cerebrospinal fluid (CSF) at diagnostic lumbar puncture in a longitudinal cohort of 192 MS patients. Through mixed-effects and machine learning models, we show that CHIT1 is a robust predictor for faster disability progression. Integrative analysis of 11 CSF and 26 central nervous system (CNS) parenchyma single-cell/nucleus RNA sequencing samples reveals CHIT1 to be predominantly expressed by microglia located in active MS lesions and enriched for lipid metabolism pathways. Furthermore, we find CHIT1 expression to accompany the transition from a homeostatic towards a more activated, MS-associated cell state in microglia. Neuropathological evaluation in post-mortem tissue from 12 MS patients confirms CHIT1 production by lipid-laden phagocytes in actively demyelinating lesions, already in early disease stages. Altogether, we provide a rationale for CHIT1 as an early biomarker for faster disability progression in MS. Here, the authors provide evidence for the potential of CHIT1 concentration in the cerebrospinal fluid at diagnostic lumbar puncture as a biomarker for disability progression in multiple sclerosis (MS) as it reflects early microglial activation in active lesions of MS patients. [ABSTRACT FROM AUTHOR]

Impairment of the central nervous system (CNS) poses a significant health risk for astronauts during long-duration space missions. In this study, we employed an innovative approach by integrating single-cell multiomics (transcriptomics and chromatin accessibility) with spatial transcriptomics to elucidate the impact of spaceflight on the mouse brain in female mice. Our comparative analysis between ground control and spaceflight-exposed animals revealed significant alterations in essential brain processes including neurogenesis, synaptogenesis and synaptic transmission, particularly affecting the cortex, hippocampus, striatum and neuroendocrine structures. Additionally, we observed astrocyte activation and signs of immune dysfunction. At the pathway level, some spaceflight-induced changes in the brain exhibit similarities with neurodegenerative disorders, marked by oxidative stress and protein misfolding. Our integrated spatial multiomics approach serves as a stepping stone towards understanding spaceflight-induced CNS impairments at the level of individual brain regions and cell types, and provides a basis for comparison in future spaceflight studies. For broader scientific impact, all datasets from this study are available through an interactive data portal, as well as the National Aeronautics and Space Administration (NASA) Open Science Data Repository (OSDR). A spatial transcriptomics and single-cell multiomics study performed on mouse brain tissue. Here, authors show region-specific spaceflight-induced alterations in processes of neurogenesis, synaptogenesis and synaptic transmission. [ABSTRACT FROM AUTHOR]

Affections of the central nervous system (CNS) rarely occur in Lyme neuroborreliosis (LNB). CNS manifestations can have residual neurological symptoms despite antibiotic treatment. We explored the spectrum of CNS affections in patients with LNB in a tertiary care center in a region endemic for Lyme borreliosis. We retrospectively included patients treated at a tertiary care center from January 2020–December 2021 fulfilling the case criteria for LNB as stated in the current German guideline on LNB. Clinical data, cerebrospinal fluid (CSF) findings and MRI imaging were collected. We included 35 patients with LNB, 24 with early manifestations and 11 with CNS-LNB. CNS-LNB patients had encephalomyelitis (n = 6) or cerebral vasculitis (n = 5). Patients with early LNB and CNS-LNB differed regarding albumin CSF/serum quotient and total protein in CSF. Duration from onset of symptoms until diagnosis was statistically significantly longer in patients with encephalomyelitis. MRI findings were heterogeneous and showed longitudinal extensive myelitis, perimedullar leptomeningeal enhancement, pontomesencephalic lesions or cerebral vasculitis. CNS-LNB can present with a variety of clinical syndromes and MRI changes. No clear pattern of MRI findings in CNS-LNB could be identified. The role of MRI consists in ruling out other causes of neurological symptoms. [ABSTRACT FROM AUTHOR]

COVID-19, caused by SARS-CoV-2, affects neuronal cells, causing several symptoms such as memory loss, anosmia and brain inflammation. Curcuminoids (Me08 e Me23) and curcumin (CUR) are derived from Curcuma Longa extract (EXT). Many therapeutic actions have been linked to these compounds, including antiviral action. Given the severe implications of COVID-19, especially within the central nervous system, our study aims to shed light on the therapeutic potential of curcuminoids against SARS-CoV-2 infection, particularly in neuronal cells. Here, we investigated the effects of CUR, EXT, Me08 and Me23 in human neuroblastoma SH-SY5Y. We observed that Me23 significantly decreased the expression of plasma membrane-associated transmembrane protease serine 2 (TMPRSS2) and TMPRSS11D, consequently mitigating the elevated ROS levels induced by SARS-CoV-2. Furthermore, Me23 exhibited antioxidative properties by increasing NRF2 gene expression and restoring NQO1 activity following SARS-CoV-2 infection. Both Me08 and Me23 effectively reduced SARS-CoV-2 replication in SH-SY5Y cells overexpressing ACE2 (SH-ACE2). Additionally, all of these compounds demonstrated the ability to decrease proinflammatory cytokines such as IL-6, TNF-α, and IL-17, while Me08 specifically reduced INF-γ levels. Our findings suggest that curcuminoid Me23 could serve as a potential agent for mitigating the impact of COVID-19, particularly within the context of central nervous system involvement. [ABSTRACT FROM AUTHOR]

Three years after SARS-CoV-2 emerged as a global infectious threat, the virus has become endemic. The neurological complications such as depression, anxiety, and other CNS complications after COVID-19 disease are increasing. The brain, and CSF have been shown as viral reservoirs for SARS-CoV-2, yielding a potential hypothesis for CNS effects. Thus, we investigated the CNS pharmacology of orally dosed nirmatrelvir/ritonavir (NMR/RTV). Using both an in vitro and an in vivo rodent model, we investigated CNS penetration and potential pharmacodynamic activity of NMR. Through pharmacokinetic modeling, we estimated the median CSF penetration of NMR to be low at 18.11% of plasma with very low accumulation in rodent brain tissue. Based on the multiples of the 90% maximal effective concentration (EC90) for SARS-CoV-2, NMR concentrations in the CSF and brain do not achieve an exposure level similar to that of plasma. A median of only 16% of all the predicted CSF concentrations in rats were > 3xEC90 (unadjusted for protein binding). This may have implications for viral persistence and neurologic post-acute sequelae of COVID-19 if increased NMR penetration in the CNS leads to decreased CNS viral loads and decreased CNS inflammation. [ABSTRACT FROM AUTHOR]

Infection with the apicomplexan protozoan Toxoplasma gondii can be life-threatening in immunocompromised hosts. Transmission frequently occurs through the oral ingestion of T. gondii bradyzoite cysts, which transition to tachyzoites, disseminate, and then form cysts containing bradyzoites in the central nervous system, resulting in latent infection. Encapsulation of bradyzoites by a cyst wall is critical for immune evasion, survival, and transmission. O-glycosylation of the protein CST1 by the mucin-type O-glycosyltransferase T. gondii (Txg) GalNAc-T3 influences cyst wall rigidity and stability. Here, we report X-ray crystal structures of TxgGalNAc-T3, revealing multiple features that are strictly conserved among its apicomplexan homologues. This includes a unique 2nd metal that is coupled to substrate binding and enzymatic activity in vitro and cyst wall O-glycosylation in T. gondii. The study illustrates the divergence of pathogenic protozoan GalNAc-Ts from their host homologues and lays the groundwork for studying apicomplexan GalNAc-Ts as therapeutic targets in disease. A Toxoplasma gondii mucin-type O-glycosyltransferase uses a unique catalytic mechanism to modify bradyzoite cyst wall proteins. A second metal coupled to substrate binding is required for catalysis, while an active site glutamate suggests a double-displacement mechanism. [ABSTRACT FROM AUTHOR]

Microglia harness an unutilized health-promoting potential in age-related neurodegenerative and neuroinflammatory diseases, conditions like progressive multiple sclerosis (MS). Our research unveils an microglia population emerging in the cortical brain regions of aging mice, marked by ERK1/2, Akt, and AMPK phosphorylation patterns and a transcriptome indicative of activated autophagy - a process critical for cellular adaptability. By deleting the core autophagy gene Ulk1 in microglia, we reduce this population in the central nervous system of aged mice. Notably, this population is found dependent on IL-34, rather than CSF1, although both are ligands for CSF1R. When aging mice are exposed to autoimmune neuroinflammation, the loss of autophagy-dependent microglia leads to neural and glial cell death and increased mortality. Conversely, microglial expansion mediated by IL-34 exhibits a protective effect. These findings shed light on an autophagy-dependent neuroprotective microglia population as a potential target for treating age-related neuroinflammatory conditions, including progressive MS. Microglia could have health-promoting capacities in age-associated neuroinflammation. Here, the authors describe an autophagy and IL-34 dependent neuroprotective microglia population in the aging brain as a potential therapeutic target. [ABSTRACT FROM AUTHOR]

The Diplostomidae include a large group of flatworms with complex life cycles and are frequently found parasitizing the eyes and central nervous system of freshwater fishes. The morphological identification of the metacercariae at species level is not always possible. Thus, molecular tools have become essential to assist in the parasite species determination. This study was aimed at describing two diplostomid metacercariae found in freshwater fish in São Paulo, Brazil, based on morphological characters and in the genetic characterization of COI sequences. Our results showed that the two recognized taxa (Tylodelphys sp. and Diplostomidae gen. sp.) appear to be different from the species already described in South America. Tylodelphys sp. differs morphologically from Tylodelphys xenopi, T. mashonense, T. jenynsiae, and T. scheuringi. The metacercariae of T. clavata and T. conifera are smaller than Tylodelphys sp., while T. podicipina is larger than the metacercariae described here. The phylogenetic analysis of COI sequences yielded Tylodelphys sp. as the sister species of Tylodelphys sp. 4, a species reported from the brain of the eleotrid Gobiomorus maculatus in Oaxaca, Mexico. The metacercariae identified as Diplostomidae gen. sp. are morphologically different from the known diplostomid metacercariae and did not match with other diplostomid sequences available. Diplostomidae gen. sp. is recovered as the sister species of Diplostomum ardeae. Although the morphological evidence and the COI sequences differentiate the metacercariae found, the absence of adult specimens of both species precludes the specific designation. This is one of the first papers that use an integrative taxonomy approach to describe the species diversity of diplostomid trematodes in Brazil. [ABSTRACT FROM AUTHOR]

The modulation of brain function and behavior by steroid hormones was classically associated with their secretion by peripheral endocrine glands. The discovery that the brain expresses the enzyme aromatase, which produces estradiol from testosterone, expanded this traditional concept. One of the best-studied roles of brain estradiol synthesis is the control of reproductive behavior. In addition, there is increasing evidence that estradiol from neural origin is also involved in a variety of non-reproductive functions. These include the regulation of neurogenesis, neuronal development, synaptic transmission, and plasticity in brain regions not directly related with the control of reproduction. Central aromatase is also involved in the modulation of cognition, mood, and non-reproductive behaviors. Furthermore, under pathological conditions aromatase is upregulated in the central nervous system. This upregulation represents a neuroprotective and likely also a reparative response by increasing local estradiol levels in order to maintain the homeostasis of the neural tissue. In this paper, we review the non-reproductive functions of neural aromatase and neural-derived estradiol under physiological and pathological conditions. We also consider the existence of sex differences in the role of the enzyme in both contexts. [ABSTRACT FROM AUTHOR]

Objective: Rosai-Dorfman disease (RDD) is a rare idiopathic, non-neoplastic histioproliferative disease. Central nervous system (CNS) manifestations are extremely rare. In this paper, we describe a 6-year-old boy with intracranial RDD mimicking multiple meningiomas both clinically and radiologically. We reviewed the literature to understand the clinical behaviour, clinicopathological features and treatment options. Methods: A PubMed (US National Library of Medicine) search using the keywords 'Rosai-Dorfman disease' and 'central nervous system' was performed and citations were reviewed. Results: Eighty-five cases of RDD involving the CNS have been reported until date, and only 7 cases involved children. Of the 85 cases, 16 cases mimicked multiple meningiomas. Our case is the first to involve multiple lesions in a child under 14 years old. Conclusion: After reviewing the literature, we concluded that RDD should be considered as a differential diagnosis for lesions mimicking multiple meningiomas, especially in children. Resection of the intracranial lesion is the most effective treatment, and a definitive diagnosis should be based on histopathologic and immunocytochemical examinations. [ABSTRACT FROM AUTHOR]

Ghrelin, a gastrointestinal hormone, is a modulator of the sense of smell. The main source of ghrelin in the central nervous system has been mainly observed in specific populations of hypothalamic neurons. An increasing number of studies have reported ghrelin synthesis and its effect on neurons outside the hypothalamus. Ghrelin and its receptors are expressed in the olfactory bulbs and in other centres of the brain, such as the amygdala, for processing olfactory signals, pyramidal neurons of the cerebral cortex and the dorsal vagal complex of the medulla oblongata. It is known that ghrelin is involved in cognitive mechanisms and eating behaviours, in fact, its expression increases in anticipation of food intake. In order to identify the existence of centrifugal direct afferents from the main olfactory bulb to the medial amygdala and the hypothalamus arcuate nucleus, in this work we used two retrograde tracers, Dil and Fluoro Gold, and immunohistochemical procedure to visualize positive ghrelin neurons. Our paper provides neuroanatomic support for the ghrelin modulation of smell. Our results show that ghrelin neuron projections from mitral cells of bulbs can transmit olfactory information via branching connections to the amygdala and the hypothalamus. This pathway could play an important role in regulating feeding behaviour in response to odours. [ABSTRACT FROM AUTHOR]