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Purpose: Knowledge of neurovascular anatomy is vital for neurosurgeons, neurologists, neuro-radiologists and anatomy students, amongst others, to fully comprehend the brain's anatomy with utmost depth. This paper aims to enhance the foundational knowledge of novice physicians in this area. Method: A comprehensive literature review was carried out by searching the PubMed and Google Scholar databases using primary keywords related to brain vasculature, without date restrictions. The identified literature was meticulously examined and scrutinized. In the process of screening pertinent papers, further articles and book chapters were obtained through analysis and additional assessing of the reference lists. Additionally, four formalin-fixed, color latex-injected cadaveric specimens preserved in 70% ethanol solution were dissected under surgical microscope (Leica Microsystems Inc, 1700 Leider Ln, Buffalo Grove, IL 60089 USA). Using microneurosurgical as well as standard instruments, and a high-speed surgical drill (Stryker Instruments 1941 Stryker Way Portage, MI 49002 USA). Ulterior anatomical dissection was documented in microscopic images. Results: Encephalic circulation functions as a complex network of intertwined vessels. The Internal Carotid Arteries (ICAs) and the Vertebral Arteries (VAs), form the anterior and posterior arterial circulations, respectively. This work provides a detailed exploration of the neurovascular anatomy of the anterior circulation and its key structures, such as the Anterior Cerebral Artery (ACA) and the Middle Cerebral Artery (MCA). Embryology is also briefly covered, offering insights into the early development of the vascular structures of the central nervous system. Cerebral venous system was detailed, highlighting the major veins and tributaries involved in the drainage of blood from the intracranial compartment, with a focus on the role of the Internal Jugular Veins (IJVs) as the primary, although not exclusive, deoxygenated blood outflow pathway. Conclusion: This work serves as initial guide, providing essential knowledge on neurovascular anatomy, hoping to reduce the initial impact when tackling the subject, albeit the intricate vasculature of the brain will necessitate further efforts to be conquered, that being crucial for neurosurgical and neurology related practice and clinical decision-making. [ABSTRACT FROM AUTHOR]

Background: The identification of biomarkers for the early diagnosis of Alzheimer's disease (AD) is a crucial goal of the current research. Blood biomarkers are less invasive, easier to obtain and achievable by a cheaper means than those on cerebrospinal fluid (CSF) and significantly more economic than functional neuroimaging investigations; thus, a great interest is focused on blood isoforms of the phosphorylated Tau protein (pTau), indicators of ongoing tau pathology (i.e. neurofibrillary tangles, NFTs, an AD neuropathological hallmark) in the central nervous system (CNS). However, current data often highlight discordant results about the ability of blood pTau to predict CSF status. Objective: We aim to synthesise the studies that compared pTau levels on CSF and blood to assess their correlation in AD continuum. Methods: We performed a narrative literature review using, first, MEDLINE (via PubMed) by means of MeSH terms, and then, we expanded the reults by means of Scopus and Web of Sciences to be as inclusive as possible. Finally, we added work following an expert opinion. Only papers presenting original data on pTau values on both blood and CSF were included. Results: The 33 included studies show an extreme heterogeneity in terms of pTau isoform (pTau181, 217 and 231), laboratory methods, diagnostic criteria and choice of comparison groups. Most studies evaluated plasma pTau181, while data on other isoforms and serum are scarcer. Discussion: Most papers identify a correlation between CSF and blood measurements. Furthermore, even when not specified, it is often possible to show an increase in blood pTau values as AD-related damage progresses in the AD continuum and higher values in AD than in other neurodegenerative diseases. Notably, plasma pTau231 seems the first biomarker to look for in the earliest and pre-clinical stages, quickly followed by pTau217 and, finally, by pTau181. Conclusions: Our results encourage the use of blood pTau for the early identification of patients with AD continuum. [ABSTRACT FROM AUTHOR]

Autosomal recessive cerebellar ataxias (ARCAs) are inherited neurological disorders that can affect both the central and peripheral nervous systems. To assess the effects of interventions according to the perception of people affected, patient-reported outcome measures (PROMs) must be available. This paper presents the development process of the Person-Reported Ataxia Impact Scale (PRAIS), a new PROM in recessive ataxias, and the documentation of its content validity, interpretability, and construct validity (structural and discriminant). The development followed the PROMIS framework and the Food and Drug Administration guidelines. A mixed-method study design was used to develop the PROM. A systematic review of the literature, semistructured interviews, and discussion groups was conducted to constitute an item pool. Experts' consultation helped formulate items, and the questionnaire was sent online to be completed by people affected. Statistical analyses were performed to assess the structural and discriminant validity. A total of 125 people affected by recessive ataxia completed the questionnaire. The factor analysis confirmed the three components: physical functions and activities, mental functions, and social functions. The statistical analysis showed that it can discriminate between stages of mobility and level of autonomy. It showed very good levels of internal consistency (0.79 to 0.89). The Person-Reported Ataxia Impact Scale (PRAIS) is a 38-item questionnaire that assesses the manifestations and impacts of the disease according to the perception of people affected by recessive ataxia. It can be used in clinical and research settings. [ABSTRACT FROM AUTHOR]

Background: Central nervous system (CNS) tumors are among the most common malignancies in various age ranges. Low-grade glioma (LGG) can account for nearly 30% of pediatric CNS malignancies. Progression or recurrence after the first-line treatments is common among these patients. Therefore, more treatments are required. Bevacizumab as an anti-VEGF antibody has come into the spotlight recently and is especially used in relapse or recurrence settings. This review aims to study the safety and efficacy of bevacizumab for patients with recurrent LGG. Methods: This study was conducted according to The Preferred Reporting Items for Systematic Reviews and Meta-Analyses. PubMed, Scopus, Web of Science, and Embase were comprehensively searched using the relevant key terms until 24th August 2023 to retrieve the studies that investigated clinical outcomes of bevacizumab in patients with recurrent LGG. All statistical analysis was performed by STATA v.17. Results: A total of 1306 papers were gathered, out of which 13 were incorporated in the meta-analysis. The pooled incidence rate of treatment according to the RANO scale was 70% (95% CI = 43–98%) for objective response rate, 26% (95% CI = 58–96%) for partial response, 21% (95% CI = 15–28%) for minor response, 14% (95% CI = 3–24%) for complete response, 48% (95% CI = 37–59%) for stable disease, and 8% (95% CI = 4–11%) for progressive disease. Furthermore, according to progressive survival after treatment, it was 4% (95% CI = −1 to 9%) for 6-month PFS, 41% (95% CI = 32–50%) for 2-year PFS, and 29% (95% CI = 22–35%) for 3-year PFS. Conclusion: According to the RANO scale and PFS, clinicians should be aware that Bevacizumab could be a favorable alternative therapy for recurrent LGG. Furthermore, bevacizumab exhibits minimal toxicity and high tolerability in recurrent LGG. [ABSTRACT FROM AUTHOR]

Despite swallowing being a frequently performed daily function, it is highly complex. For a safe swallow to occur, muscles within the head, neck, and thorax need to contract in a concerted pattern, controlled by several swallowing centers at multiple levels of the central nervous system, including the midbrain, cerebral cortex, and cerebellum in addition to five cranial nerves. Dysphagia, or difficulty swallowing, is caused by a long list of pathologic processes and diseases, which can interfere with various stages along the swallowing sensorimotor pathway. When present, dysphagia leads to increased mortality, morbidity, hospital length of stay, and reduced quality of life. Current dysphagia management approaches, such as altering the texture and consistency of foods and fluids and teaching patients rehabilitative exercises, have been broadly unchanged for many years and, in the case of texture modification, are of uncertain effectiveness. However, evidence is emerging in support of new medication-based and neuromodulatory treatment approaches. Regarding medication-based therapies, most research has focused on capsaicinoids, which studies have shown are able to improve swallowing in patients with post-stroke dysphagia. Separately, albeit convergently, in the field of neuromodulation, there is a growing and positive evidential base behind three non-invasive brain stimulation techniques: repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (TDCS), and pharyngeal electrical stimulation (PES). Should some or all of these emerging therapies fulfill their promise, dysphagia-related patient outcomes may be improved. This paper describes the current state of our understanding regarding new medication and neuromodulation-based neurogenic oropharyngeal dysphagia treatments. [ABSTRACT FROM AUTHOR]

Annexins, a group of Ca2+-dependent phospholipid-binding proteins, exert diverse roles in neuronal development, normal central nervous system (CNS) functioning, neurological disorders, and CNS tumors. This paper reviews the roles of individual annexins (A1-A13) in these contexts. Annexins possess unique structural and functional features, such as Ca2+-dependent binding to phospholipids, participating in membrane organization, and modulating cell signaling. They are implicated in various CNS processes, including endocytosis, exocytosis, and stabilization of plasma membranes. Annexins exhibit dynamic roles in neuronal development, influencing differentiation, proliferation, and synaptic formation in CNS tissues. Notably, annexins such as ANXA1 and ANXA2 play roles in apoptosis and blood-brain barrier (BBB) integrity. Neurological disorders, including Alzheimer's disease, multiple sclerosis, and depression, involve annexin dysregulation, influencing neuroinflammation, blood-brain barrier integrity, and stress responses. Moreover, annexins contribute to the pathogenesis of CNS tumors, either promoting or suppressing tumor growth, angiogenesis, and invasion. Annexin expression patterns vary across different CNS tumor types, providing potential prognostic markers and therapeutic targets. This review underscores the multifaceted roles of annexins in the CNS, highlighting their importance in normal functioning, disease progression, and potential therapeutic interventions. [ABSTRACT FROM AUTHOR]

In this paper, for the first time, we showed that an Internode Segment (INS) of a myelinated axon acts as a lowpass filter, and its filter characteristics depend on the number of myelin turns. Consequently, we showed how the representability of a neural signal could be altered with myelin loss in pathological conditions involving demyelinating diseases. Contrary to the traditionally held viewpoint that myelin geometry of an INS is optimised for maximising Conduction Velocity (CV) of Action Potential (AP), our theory provides an alternative viewpoint that myelin geometry of an INS is optimised for maximizing representability of the stimuli a fibre is meant to carry. Subsequently, we show that this new viewpoint could explain hitherto unexplained experimentally observed phenomena such as, shortening of INS length during demyelination and remyelination, and non-uniform distribution of INS in the central nervous system fibres and associated changes in diameter of nodes of ranvier along an axon. Finally, our theory indicates that a compensatory action could take place during demyelination up to a certain number of loss of myelin turns to preserve the neural signal representability by simultaneous linear scaling of the length of an INS and the inner radius of the fibre. [ABSTRACT FROM AUTHOR]

Brain-computer interfaces (BCIs) allow direct communication between one's central nervous system and a computer without any muscle movement hence by-passing the peripheral nervous system. They can restore disabled people's ability to interact with their environment, e.g. communication and wheelchair control. However, to this day their performance is still hindered by the non-stationarity of electroencephalography (EEG) signals, as well as their susceptibility to noise from the users' environment and from their own physiological activity. Moreover, a non-negligible amount of users struggle to use BCI systems based on motor imagery. In this paper, a new method based on the path signature is introduced to tackle this problem by using features which are different from the usual power-based ones. The path signature is a series of iterated integrals computed from a multidimensional path. It is invariant under translation and time reparametrization, which makes it a robust feature for multichannel EEG time series. The performance can be further boosted by combining the path signature with the gold standard Riemannian classifier in the BCI field exploiting the geometric structure of symmetric positive definite (SPD) matrices. The results obtained on publicly available datasets show that the signature method is more robust to inter-user variability than classical ones, especially on noisy and low-quality data. Hence, this study paves the way towards the use of mathematical tools that until now have been neglected, in order to tackle the EEG-based BCI variability issue. It also sheds light on the lead-lag relationship captured by path signature which seems relevant to assess the underlying neural mechanisms. [ABSTRACT FROM AUTHOR]

Clear cell meningiomas are a rare histological subtype of World Health Organization (WHO) grade II meningioma. Despite its relatively low frequency, clear cell meningioma has attracted considerable attention because of its unique pathological characteristics, clinical behavior, and challenging management considerations. The purpose of our systematic review is to provide clinicians with a better understanding of this rare disease. PubMed was searched for articles in the English language published from 1988 to 2023 June. The keywords were as follows: "clear cell meningioma," "clear cell" and "meningioma." We analyzed clinical manifestations, radiological manifestations, pathological features, comprehensive treatment strategies, and prognosis to determine the factors influencing recurrence-free survival (RFS). Recurrence-free survival curves of related factors were calculated by the Kaplan‒Meier method. The log-rank test and Cox univariate analysis were adopted to assess the intergroup differences and seek significant factors influencing prognosis and recurrence. Fifty-seven papers met the eligibility criteria, including 207 cases of clear cell meningioma (CCM), which were confirmed by postoperative pathology. The fifty-seven articles involved 84 (40.6%) males and 123 (59.4%) females. The average age at diagnosis was 27.9 years (range, 14 months to 84 years). Among the symptoms observed, headache, neurologic deficit, and hearing loss were the most commonly reported clinical manifestations. Most tumors (47.8%) were located in the skull base region. Most tumors showed significant enhancement, and homogeneous enhancement was more common. A total of 152 (74.1%) patients underwent gross total resection (GTR), and 53 (25.9%) patients underwent subtotal resection (STR). During the follow-up, the tumor recurred in 80 (39.4%) patients. The log-rank test and the Cox univariate analysis revealed that tumor resection range (GTR vs. STR) and adjuvant treatment (YES vs. NO) were significant predictors of recurrence-free survival (RFS). Clear cell meningioma is a rare type of meningioma with challenging diagnosis and therapy. The prognosis of this disease is different from that of regular meningiomas. Recurrence remains a possibility even after total tumor resection. We found that the surgical resection range and adjuvant treatment affected the recurrence period. This finding provides significant guidance for the treatment of clear cell meningioma. [ABSTRACT FROM AUTHOR]

Hyponatremia is a common electrolyte abnormality with important prognostic and therapeutic implications. It might exert detrimental effects on various organ systems including the central nervous system (CNS), bone, and heart along with its potential association with poor quality of life. These adverse effects might be largely mediated through a variety of mechanisms including osmotic stress, dysfunctional transmembrane exchangers, and enhanced oxidative stress. Interestingly, hyponatremia might also have an important association with takotsubo syndrome (TTS) that has been universally considered as a reversible form of cardiomyopathy usually emerging in response to various stressors. In this context, severe hyponatremia was previously reported to serve as a direct trigger of TTS evolution largely through its potential impact on CNS and heart. However, pathogenetic and clinical implications of hyponatremia still need to be thoroughly evaluated in patients with TTS. This paper aims to analyze the clinical features of published cases with TTS primarily triggered by hyponatremia and also aims to discuss the association between hyponatremia and TTS from a broader perspective. [ABSTRACT FROM AUTHOR]

In this study, we introduce a novel maze task designed to investigate naturalistic motor learning in bimanual coordination. We developed and validated an extended set of movement primitives tailored to capture the full spectrum of scenarios encountered in a maze game. Over a 3-day training period, we evaluated participants' performance using these primitives and a custom-developed software, enabling precise quantification of performance. Our methodology integrated the primitives with in-depth kinematic analyses and thorough thumb pressure assessments, charting the trajectory of participants' progression from novice to proficient stages. Results demonstrated consistent improvement in maze performance and significant adaptive changes in joint behaviors and strategic recalibrations in thumb pressure distribution. These findings highlight the central nervous system's adaptability in orchestrating sophisticated motor strategies and the crucial role of tactile feedback in precision tasks. The maze platform and setup emerge as a valuable foundation for future experiments, providing a tool for the exploration of motor learning and coordination dynamics. This research underscores the complexity of bimanual motor learning in naturalistic environments, enhancing our understanding of skill acquisition and task efficiency while emphasizing the necessity for further exploration and deeper investigation into these adaptive mechanisms. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of motor neurons in the central nervous system (CNS). Mutations in the metalloenzyme SOD1 are associated with inherited forms of ALS and cause a toxic gain of function thought to be mediated by dimer destabilization and misfolding. SOD1 binds two Cu and two Zn ions in its homodimeric form. We have applied native ambient mass spectrometry imaging to visualize the spatial distributions of intact metal-bound SOD1G93A complexes in SOD1G93A transgenic mouse spinal cord and brain sections and evaluated them against disease pathology. The molecular specificity of our approach reveals that metal-deficient SOD1G93A species are abundant in CNS structures correlating with ALS pathology whereas fully metalated SOD1G93A species are homogenously distributed. Monomer abundance did not correlate with pathology. We also show that the dimer-destabilizing post-translational modification, glutathionylation, has limited influence on the spatial distribution of SOD1 dimers. In this work, protein-metal complexes implicated in the pathogenesis of amyotrophic lateral sclerosis were mapped by mass spectrometry imaging. Metal-deficient hSOD1G93A complexes were revealed to be localised with disease pathology in the spinal cord and brain. [ABSTRACT FROM AUTHOR]

The discovery of new classes of regulatory molecules in human and animal metabolism always leads to a large-scale study of their properties in the context of biochemistry, physiology, and pharmacology. About 20 years ago, hydrogen sulfide (H2S) and its derivatives called reactive sulfur species (RSS), such as persulfides, polysulfides, nitrosothiols, sulfenic acids, and others became one of such classes of molecules. The participation of RSS in a variety of physiological and pathological processes, including the regulation of vascular tone, inflammation, long-term potentiation in the central nervous system, etc., has been shown. Changes in RSS levels or patterns of modification of their targets are associated with a wide range of cardiovascular, oncological, neurodegenerative, and other pathologies. For a part of these processes, mechanisms have been studied that involve direct modification of regulatory (NF-κB, Keap1) or effector (GAFD, eNOS, TRPA1) proteins through reactions of cysteine residues and metal-containing centers with APS. The presence of different regulated enzymatic systems producing RSS and numerous molecular targets allows us to consider H2S and its derivatives as an important class of small regulatory molecules. H2S is belongs to the class of so-called "gasotransmitters," along with nitric oxide (II) and carbon monoxide. Over the last 20 years, a vast amount of data on the biochemistry of these compounds and approaches to their study has been accumulated. [ABSTRACT FROM AUTHOR]

The muscle system and the FMRFamide immunopositive components of the nervous system of flatworms Acrolichanus auriculatus (Digenea, Allocreadiidae), an intestine parasite of acipenserid fishes, were studied for the first time by immunocytochemical, histochemical methods and confocal laser scanning microscopy. Scanning electron microscopy in A. auriculatus revealed a consistent pattern in the number and arrangement of ciliated and unciliated sensory papillae along the digenean body. Morphological data demonstrated the presence of the circular, longitudinal and diagonal muscles in different body regions of A. auriculatus. The musculature of the oral and ventral suckers, the digestive system, as well as the muscles extending radially from the genital pore are described. The study revealed the presence of the FMRFamide immunopositive staining in the central and peripheral nervous systems of A. auriculatus: in the neurons and neurites of the brain, brain commissure, in three pairs of the longitudinal nerve cords and commissures. FMRFamide immunopositive nerve elements innervate the attachment organs and the compartments of the digestive, reproductive and excretory systems. [ABSTRACT FROM AUTHOR]

Maintenance of autonomic homeostasis is continuously calibrated by sensory fibers of the vagus nerve and sympathetic chain that convey compound action potentials (CAPs) to the central nervous system. Lipopolysaccharide (LPS) intravenous challenge reliably elicits a robust inflammatory response that can resemble systemic inflammation and acute endotoxemia. Here, we administered LPS intravenously in nine healthy subjects while recording ventral cervical magnetoneurography (vcMNG)-derived CAPs at the rostral Right Nodose Ganglion (RNG) and the caudal Right Carotid Artery (RCA) with optically pumped magnetometers (OPM). We observed vcMNG RNG and RCA neural firing rates that tracked changes in TNF-α levels in the systemic circulation. Further, endotype subgroups based on high and low IL-6 responders segregate RNG CAP frequency (at 30-120 min) and based on high and low IL-10 response discriminate RCA CAP frequency (at 0-30 min). These vcMNG tools may enhance understanding and management of the neuroimmune axis that can guide personalized treatment based on an individual's distinct endophenotype. Ventral cervical magnetoneurography responses after LPS administration temporally aligned with the changes in TNF-α levels, making it a potential sensitive bioindicator of the neuroimmune axis for clinical use. [ABSTRACT FROM AUTHOR]

The central nervous system (CNS) includes anatomically distinct macrophage populations including parenchyma microglia and CNS-associated macrophages (CAMs) localized at the interfaces like meninges and perivascular space, which play specialized roles for the maintenance of the CNS homeostasis with the help of precisely controlled gene expressions. However, the transcriptional machinery that determines their cell-type specific states of microglia and CAMs remains poorly understood. Here we show, by myeloid cell-specific deletion of transcription factors, IRF8 and MAFB, that both adult microglia and CAMs utilize IRF8 to maintain their core gene signatures, although the genes altered by IRF8 deletion are different in the two macrophage populations. By contrast, MAFB deficiency robustly affected the gene expression profile of adult microglia, whereas CAMs are almost independent of MAFB. Our data suggest that distinct transcriptional machineries regulate different macrophages in the CNS. The authors show that the transcription factors IRF8 and MAFB differentially alter the gene expression profiles of different resident macrophages, which might contribute to their functional diversity within the central nervous system. [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]

Dopamine (DA) is a catecholamine neurotransmitter widely distributed in the central nervous system. It participates in various physiological functions, such as feeding, anxiety, fear, sleeping and arousal. The regulation of feeding is exceptionally complex, involving energy homeostasis and reward motivation. The reward system comprises the ventral tegmental area (VTA), nucleus accumbens (NAc), hypothalamus, and limbic system. This paper illustrates the detailed mechanisms of eight typical orexigenic and anorexic neuropeptides that regulate food intake through the reward system. According to recent literature, neuropeptides released from the hypothalamus and other brain regions regulate reward feeding predominantly through dopaminergic neurons projecting from the VTA to the NAc. In addition, their effect on the dopaminergic system is mediated by the prefrontal cortex, paraventricular thalamus, laterodorsal tegmental area, amygdala, and complex neural circuits. Research on neuropeptides involved in reward feeding can help identify more targets to treat diseases with metabolic disorders, such as obesity. [ABSTRACT FROM AUTHOR]

Background: Protocadherin 10 (PCDH 10), a member of the superfamily of protocadherins, is a Ca2+-dependent homophilic cell-cell adhesion molecule expressed on the surface of cell membranes. Protocadherin 10 plays a critical role in the central nervous system including in cell adhesion, formation and maintenance of neural circuits and synapses, regulation of actin assembly, cognitive function and tumor suppression. Additionally, Pcdh10 can serve as a non-invasive diagnostic and prognostic indicator for various cancers. Methods: This paper collects and reviews relevant literature in Pubmed. Conclusion: This review describes the latest research understanding the role of Pcdh10 in neurological disease and human cancer, highlighting the importance of scrutinizing its properties for the development of targeted therapies and identifying a need for further research to explore Pcdh10 functions in other pathways, cell types and human pathologies. [ABSTRACT FROM AUTHOR]

Major research breakthroughs over the past 30 years in the field of substance use prevention have served to: (1) enhance understanding of pharmacological effects on the central and peripheral nervous systems and the health and social consequences of use of psychoactive substances, particularly for children and adolescents; (2) delineate the processes that increase vulnerability to or protect from initiation of substance use and progression to substance use disorders (SUDs) and, based on this understanding, (3) develop effective strategies and practices to prevent the initiation and escalation of substance use. The challenge we now face as a field is to "normalize" what we have learned from this research so that it is incorporated into the work of those involved in supporting, planning, and delivering prevention programming to populations around the world, is integrated into health and social service systems, and helps to shape public policies. But we wish to go further, to incorporate these effective prevention practices into everyday life and the mind-sets of the public, particularly parents and educators. This paper reviews the advances that have been made in the field of prevention and presents a framework and recommendations to achieve these objectives generated during several meetings of prevention and implementation science researchers sponsored by the International Consortium of Universities for Drug Demand Reduction (ICUDDR) that guides a roadmap to achieve "normalization." [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a progressive disease that often affects the cerebellum. It is characterised by demyelination, inflammation, and neurodegeneration within the central nervous system. Damage to the cerebellum in MS is associated with increased disability and decreased quality of life. Symptoms include gait and balance problems, motor speech disorder, upper limb dysfunction, and oculomotor difficulties. Monitoring symptoms is crucial for effective management of MS. A combination of clinical, neuroimaging, and task-based measures is generally used to diagnose and monitor MS. This paper reviews the present and new tools used by clinicians and researchers to assess cerebellar impairment in people with MS (pwMS). It also describes recent advances in digital and home-based monitoring for people with MS. [ABSTRACT FROM AUTHOR]

Leukoencephalopathy with calcifications and cysts (LCC; OMIM #614561) is a rare disease and at present there are less than 100 cases reported worldwide. Mutations in the SNORD118 gene is now known to be the cause of LCC. We present a case who was heterozygous for the n.70G>A and n.6C>T sequence variants of the SNORD118 gene, variants which to date have not been described. Compared with the cases that we reviewed, our patient had the second longest time to diagnosis (age 56) from onset of symptoms 40 years prior. Moreover, his cousin's family has a high prevalence of epilepsy. This paper reviewed all published reports to date that had descriptive cases involving LCC as well as testing for the SNORD118 gene. Since 1996 only 85 patients have been described in 59 case reports. In this review, we summarize their clinical features, especially central nervous system symptoms, treatment, pathology, and gene testing results. [ABSTRACT FROM AUTHOR]

Spina bifida is a serious birth defect affecting the central nervous system, characterized by incomplete closure of the neural tube. Ethiopia has a very high prevalence of spina bifida, affecting about 40 cases per 10,000 births. Babies born with spina bifida require early closure surgery, done within the first 2–3 days after birth. Some babies need repeat surgeries to address complications, including hydrocephalus. Without medical care, babies have a high risk of death within the first 5 years of their life. Neurosurgical capacity for spina bifida closure surgery at birth is a relatively new development in Ethiopia. ReachAnother Foundation, a not-for-profit organization based in OR, USA, started work in Ethiopia in 2009 and has been instrumental in training neurosurgeons and improving treatment for spina bifida and hydrocephalus. Along with the development of neurosurgical care, the Foundation has invested in training multi-disciplinary teams to conduct patient aftercare and has launched a platform for improved patient outcomes research. As of year 2022, they support six spina bifida "Centers of Excellence" nationwide and are continuously advocating for primary prevention of spina bifida through mandatory fortification of staple foods in Ethiopia. This paper describes ReachAnother's efforts in Ethiopia in a short interval of time, benefiting numerous patients and families with spina bifida and anencephaly. We document this as a case study for other countries to model where resources are limited and the prevalence of spina bifida and hydrocephalus is high, especially in Asia and Africa. [ABSTRACT FROM AUTHOR]

The paper considers the structure of intermuscular synergetic interaction that ensures the athlete's body stopping on the trampoline after a jump. We compared the spatio-temporal characteristics of muscle synergies extracted from the skeletal muscles electroactivity amplitude and frequency of biopotentials data. The objective of the study was to find out whether the extracted kinematic modules represent the central mechanisms for the movement structure controlling as well as to determine the variables which should be stabilized by muscle synergies activity. The extraction of synergies was carried out using the matrix factorization method. It has been established that trampoline jump stopping can be performed using common patterns of muscle synergies spatio-temporal activation. The synergistic effects obtained using different approaches of instrumental assessment of skeletal muscle electroactivity probably reflect different control mechanisms implemented at different levels of the central nervous system. Muscle synergies are aimed at the stabilizing of the certain anthropometric points movement, as well as body segments, combined into kinematic modules. The structure of the kinematic modules themselves indicates the effective organization of intermuscular interaction, indirectly reflecting the central control mechanisms of complex multi-joint movement. [ABSTRACT FROM AUTHOR]

This paper presents an automated approach to perform multiclass classification of four majorly diagnosed Central nervous system brain tumors. The Astrocytoma, Glioblastoma multiforme, Meningioma and Oligodendroglioma are the four types of central nervous system brain tumors types, whose classification is being performed with the aid of this proposed approach. In addition, this proposed approach also used to perform binary classification of Glioma brain tumors into low grade and high grade Glioma tumor. The proposed automated approach for multiclass and binary class classification is based on the threshold segmentation of fused Magnetic Resonance Imaging sequences, proposed hybrid feature extraction methods along with shape based features and ensemble learning classifier. The two hybrid feature extraction methods are proposed in this paper, one based on the Discrete wavelet transform + Gradient Grey level co-occurrences matrix and second one based on the Discrete wavelet transform + Local binary pattern + Grey level run length matrix. The extracted texture features along with the shape based features are further reduced employing Principal component analysis. The resulted selected features are finally used to train the majority voting based ensemble classifier model with the aid of Central nervous system local dataset, Brain Tumor Segmentation 2013 and 2015 global dataset. The proposed automated system delivers an accuracies of 99.12, 95.24, 97.62 and 97.62 for the correct classification of Astrocytoma, Glioblastoma multiforme, Meningioma and Oligodendroglioma over the Central nervous system local dataset. Whereas delivers an accuracy of 100 and 99.52 for the binary classification of Glioma on the Brain Tumor Segmentation 2013 and 2015 global datasets employing 10-fold cross validation. [ABSTRACT FROM AUTHOR]

This paper investigates externalities generated by air transportation pollution on health. As a source of exogenous variation, we use an unannounced 5-month trial that reallocated early morning aircraft landings at London Heathrow Airport. Our measure of health is prescribed medications spending on conditions known to be aggravated by pollution, especially sleep disturbances. We observe a significant and substantial decrease in prescribed drugs for respiratory and central nervous system disorders in the areas subjected to reduced air travel between 4:30 am and 6.00 am compared with the control regions. Our findings suggest a causal influence of aviation on health conditions. [ABSTRACT FROM AUTHOR]

The use of magnetic resonance imaging (MRI) in the evaluation of the central extracranial nervous system, namely the brachial and lumbosacral plexuses, is well established and has been performed for many years. Only recently after numerous advances in MRI, has image quality been sufficient to properly visualize small structures, such as nerves in the extremities. Despite the advances, peripheral MR Neurography remains a complex and difficult examination to perform, especially in the pediatric patient population, in which the risk for motion artifact and compliance is always of concern. Thus, technical aspects of the MR imaging protocol must be flexible but robust, to balance image quality with scan time, in a patient population of varying sizes. An additional important step for reliably performing a successful MR Neurography examination is the non-technical pre-imaging preparation, which includes patient/family education and open communication with referring teams. This paper will discuss in detail the individual technical and non-technical/operational aspects of peripheral MR Neurography, to help guide in building a successful program in the pediatric population. [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]

Astrocytes are glycolytically active cells in the central nervous system playing a crucial role in various brain processes from homeostasis to neurotransmission. Astrocytes possess a complex branched morphology, frequently examined by fluorescent microscopy. However, staining and fixation may impact the properties of astrocytes, thereby affecting the accuracy of the experimental data of astrocytes dynamics and morphology. On the other hand, phase contrast microscopy can be used to study astrocytes morphology without affecting them, but the post-processing of the resulting low-contrast images is challenging. The main result of this work is a novel approach for recognition and morphological analysis of unstained astrocytes based on machine-learning recognition of microscopic images. We conducted a series of experiments involving the cultivation of isolated astrocytes from the rat brain cortex followed by microscopy. Using the proposed approach, we tracked the temporal evolution of the average total length of branches, branching, and area per astrocyte in our experiments. We believe that the proposed approach and the obtained experimental data will be of interest and benefit to the scientific communities in cell biology, biophysics, and machine learning. [ABSTRACT FROM AUTHOR]

Selective activation of individual subtypes of muscarinic receptors is a promising way to safely alleviate a wide range of pathological conditions in the central nervous system and the periphery as well. The flexible G-protein interface of muscarinic receptors allows them to interact with several G-proteins with various efficacy, potency, and kinetics. Agonists biased to the particular G-protein mediated pathway may result in selectivity among muscarinic subtypes and, due to the non-uniform expression of individual G-protein alpha subunits, possibly achieve tissue specificity. Here, we demonstrate that novel tetrahydropyridine-based agonists exert specific signalling profiles in coupling with individual G-protein α subunits. These signalling profiles profoundly differ from the reference agonist carbachol. Moreover, coupling with individual Gα induced by these novel agonists varies among subtypes of muscarinic receptors which may lead to subtype selectivity. Thus, the novel tetrahydropyridine-based agonist can contribute to the elucidation of the mechanism of pathway-specific activation of muscarinic receptors and serve as a starting point for the development of desired selective muscarinic agonists. [ABSTRACT FROM AUTHOR]

The adverse use of alcohol is a serious global public health problem. Maternal alcohol consumption during pregnancy usually causes prenatal alcohol exposure (PAE) in the developing fetus, leading to a spectrum of disorders known as fetal alcohol spectrum disorders (FASD) and even fetal alcohol syndrome (FAS) throughout the lifelong sufferers. The prevalence of FASD is approximately 7.7 per 1,000 worldwide, and is even higher in developed regions. Generally, Ethanol in alcoholic beverages can impair embryonic neurological development through multiple pathways leading to FASD. Among them, the leading mechanism of FASDs is attributed to ethanol-induced neuroinflammatory damage to the central nervous system (CNS). Although the underlying molecular mechanisms remain unclear, the remaining multiple pathological mechanisms is likely due to the neurotoxic damage of ethanol and the resultant neuronal loss. Regardless of the molecular pathway, the ultimate outcome of the developing CNS exposed to ethanol is almost always the destruction and apoptosis of neurons, which leads to the reduction of neurons and further the development of FASD. In this review, we systematically summarize the current research progress on the pathogenesis of FASD, which hopefully provides new insights into differential early diagnosis, treatment and prevention for patents with FASD. [ABSTRACT FROM AUTHOR]

The phenomenal diversity of neuronal types in the central nervous system is achieved in part by the asymmetric division of neural precursors. In zebrafish neural precursors, asymmetric dispatch of Sara endosomes (with its Notch signaling cargo) functions as fate determinant which mediates asymmetric division. Here, we found two distinct pools of neural precursors based on Sara endosome inheritance and spindle-microtubule enrichment. Symmetric or asymmetric levels of spindle-microtubules drive differently Sara endosomes inheritance and predict neural precursor lineage. We uncover that CAMSAP2a/CAMSAP3a and KIF16Ba govern microtubule asymmetry and endosome motility, unveiling the heterogeneity of neural precursors. Using a plethora of physical and cell biological assays, we determined the physical parameters and molecular mechanisms behind microtubule asymmetries and biased endosome motility. Evolutionarily, the values of those parameters explain why all sensory organ precursor cells are asymmetric in flies while, in zebrafish spinal cord, two populations of neural precursors (symmetric vs asymmetric) are possible. In Zebrafish embryos spinal cords, neural precursors are clustered in two distinct populations based on their spindle-microtubule enrichment. KIF16Ba, CAMSAP2a/3a and spindle-microtubule enrichment control Sara endosome motility and mediate neural precursor fates. [ABSTRACT FROM AUTHOR]

The Alanine-Serine-Cysteine transporter 1 (Asc-1 or SLC7A10) forms a crucial heterodimeric transporter complex with 4F2hc (SLC3A2) through a covalent disulfide bridge. This complex enables the sodium-independent transport of small neutral amino acids, including L-Alanine (L-Ala), Glycine (Gly), and D-Serine (D-Ser), within the central nervous system (CNS). D-Ser and Gly are two key endogenous glutamate co-agonists that activate N-methyl-d-aspartate (NMDA) receptors by binding to the allosteric site. Mice deficient in Asc-1 display severe symptoms such as tremors, ataxia, and seizures, leading to early postnatal death. Despite its physiological importance, the functional mechanism of the Asc-1-4F2hc complex has remained elusive. Here, we present cryo-electron microscopy (cryo-EM) structures of the human Asc-1-4F2hc complex in its apo state, D-Ser bound state, and L-Ala bound state, resolved at 3.6 Å, 3.5 Å, and 3.4 Å, respectively. Through detailed structural analysis and transport assays, we uncover a comprehensive alternating access mechanism that underlies conformational changes in the complex. In summary, our findings reveal the architecture of the Asc-1 and 4F2hc complex and provide valuable insights into substrate recognition and the functional cycle of this essential transporter complex. The human Asc-1-4F2hc complex plays an important role in the neural development and stability. Here, authors determine the cryo-EM structures of Asc-1-4F2hc complex in three states, revealing its substrate recognition and transport mechanism. [ABSTRACT FROM AUTHOR]

The motor neuroscience literature suggests that the central nervous system may encode some motor commands in terms of velocity. In this work, we tackle the question: what consequences would velocity commands produce at the behavioral level? Considering the ubiquitous presence of noise in the neuromusculoskeletal system, we predict that velocity commands affected by stationary noise would produce "random walks", also known as Brownian processes, in position. Brownian motions are distinctively characterized by a linearly growing variance and a power spectral density that declines in inverse proportion to frequency. This work first shows that these Brownian processes are indeed observed in unbounded motion tasks e.g., rotating a crank. We further predict that such growing variance would still be present, but bounded, in tasks requiring a constant posture e.g., maintaining a static hand position or quietly standing. This hypothesis was also confirmed by experimental observations. A series of descriptive models are investigated to justify the observed behavior. Interestingly, one of the models capable of accounting for all the experimental results must feature forward-path velocity commands corrupted by stationary noise. The results of this work provide behavioral support for the hypothesis that humans plan the motion components of their actions in terms of velocity. [ABSTRACT FROM AUTHOR]

Recent cryoEM studies elucidated details of the structural basis for the substrate selectivity and translocation of heteromeric amino acid transporters. However, Asc1/CD98hc is the only neutral heteromeric amino acid transporter that can function through facilitated diffusion, and the only one that efficiently transports glycine and D-serine, and thus has a regulatory role in the central nervous system. Here we use cryoEM, ligand-binding simulations, mutagenesis, transport assays, and molecular dynamics to define human Asc1/CD98hc determinants for substrate specificity and gain insights into the mechanisms that govern substrate translocation by exchange and facilitated diffusion. The cryoEM structure of Asc1/CD98hc is determined at 3.4–3.8 Å resolution, revealing an inward-facing semi-occluded conformation. We find that Ser 246 and Tyr 333 are essential for Asc1/CD98hc substrate selectivity and for the exchange and facilitated diffusion modes of transport. Taken together, these results reveal the structural bases for ligand binding and transport features specific to human Asc1. Asc1/CD98hc is a key regulator of small neutral amino acid transport in the brain and adipose tissue. Here, authors report the structure of semi-occluded hAsc1/CD98hc and provide a model for Asc1 exchange and facilitated diffusion modes of transport. [ABSTRACT FROM AUTHOR]

Neurological disorders, including spinal cord injury, peripheral nerve injury, traumatic brain injury, and neurodegenerative diseases, pose significant challenges in terms of diagnosis, treatment, and understanding the underlying pathophysiological processes. Label-free multiphoton microscopy techniques, such as coherent Raman scattering, two-photon excited autofluorescence, and second and third harmonic generation microscopy, have emerged as powerful tools for visualizing nervous tissue with high resolution and without the need for exogenous labels. Coherent Raman scattering processes as well as third harmonic generation enable label-free visualization of myelin sheaths, while their combination with two-photon excited autofluorescence and second harmonic generation allows for a more comprehensive tissue visualization. They have shown promise in assessing the efficacy of therapeutic interventions and may have future applications in clinical diagnostics. In addition to multiphoton microscopy, vibrational spectroscopy methods such as infrared and Raman spectroscopy offer insights into the molecular signatures of injured nervous tissues and hold potential as diagnostic markers. This review summarizes the application of these label-free optical techniques in preclinical models and illustrates their potential in the diagnosis and treatment of neurological disorders with a special focus on injury, degeneration, and regeneration. Furthermore, it addresses current advancements and challenges for bridging the gap between research findings and their practical applications in a clinical setting. [ABSTRACT FROM AUTHOR]

During forward swinging of the arm, the central nervous system must anticipate the effect of upraising upon the body. Little is known about the cerebellar network that coordinates these anticipatory postural adjustments (APAs). Stimulating different cerebellar regions with transcranial direct current stimulation (tDCS) and with different polarities modulated the APAs. We used surface electromyography (sEMG) to measure muscle activities in a bilateral rapid shoulder flexion task. The onset of APAs was altered after tDCS over the vermis, while the postural stability and the kinematics of arm raising were not affected. To our knowledge, this is the first human cerebellar-tDCS (c-tDCS) study to separate cerebellar involvement in core muscle APAs in bilateral rapid shoulder flexion. These data contribute to our understanding of the cerebellar network supporting APAs in healthy adults. Modulated APAs of the erector spinae by tDCS on the vermis may be related to altered cerebellar brain inhibition (CBI), suggesting the importance of the vermal-cerebral connections in APAs regulation. [ABSTRACT FROM AUTHOR]

Congenital melanocytic naevus (CMN) syndrome, previously termed neurocutaneous melanosis, is a rare disease caused by postzygotic mosaic mutations occurring during embryogenesis in precursors of melanocytes. The severity of neurological manifestations in CMN patients is related to central nervous system abnormalities found at magnetic resonance imaging. The association between CMN and Dandy–Walker malformation (DWM) has been described in the literature, but recent advances in imaging and genetics lead to diagnostic criteria revision. In this paper, we aim to re-evaluate the proposed association by reviewing the available literature and present a patient with CMN and a large posterior fossa cyst. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs), including exosomes, microvesicles, and oncosomes, are nano-sized particles enclosed by a lipid bilayer. EVs are released by virtually all eukaryotic cells and have been shown to contribute to intercellular communication by transporting proteins, lipids, and nucleic acids. In the context of neurodegenerative diseases, EVs may carry toxic, misfolded forms of amyloidogenic proteins and facilitate their spread to recipient cells in the central nervous system (CNS). CNS-originating EVs can cross the blood–brain barrier into the bloodstream and may be found in other body fluids, including saliva, tears, and urine. EVs originating in the CNS represent an attractive source of biomarkers for neurodegenerative diseases, because they contain cell- and cell state-specific biological materials. In recent years, multiple papers have reported the use of this strategy for identification and quantitation of biomarkers for neurodegenerative diseases, including Parkinson's disease and atypical parkinsonian disorders. However, certain technical issues have yet to be standardized, such as the best surface markers for isolation of cell type-specific EVs and validating the cellular origin of the EVs. Here, we review recent research using CNS-originating EVs for biomarker studies, primarily in parkinsonian disorders, highlight technical challenges, and propose strategies for overcoming them. [ABSTRACT FROM AUTHOR]

The paper presents the motor synergies' structure at the muscular and kinematic levels of their study during performing various sports balance postures. The features of the formation and modification of synergetic modules depending on the motor task are considered. An attempt is made to combine some computational aspects applied according of various concepts of synergetic control. The tools for identifying and analyzing synergy parameters included regression analysis and data factorization methods. It has been established that differing in biomechanical structure balance exercises can be realized using common patterns of kinematic synergies spatial organization, however, at the muscular level, the existence of common spatial activation profiles is not obvious. The presence of several different time patterns of synergy activation in the structure of each balance exercise has been revealed, which may be associated with various motor control strategies in the central nervous system. The structure of kinematic synergies may be influenced by artificial degrees of freedom restriction, unrelated to central control processes. It is shown that the inclusion of the concept of "variables' area" in the motor control modular organization theory contributes to the convergence of existing motor control concepts based on synergy principle. [ABSTRACT FROM AUTHOR]

Brain metastasis (BM) is one of the main complications of many cancers, and the most frequent malignancy of the central nervous system. Imaging studies of BMs are routinely used for diagnosis of disease, treatment planning and follow-up. Artificial Intelligence (AI) has great potential to provide automated tools to assist in the management of disease. However, AI methods require large datasets for training and validation, and to date there have been just one publicly available imaging dataset of 156 BMs. This paper publishes 637 high-resolution imaging studies of 75 patients harboring 260 BM lesions, and their respective clinical data. It also includes semi-automatic segmentations of 593 BMs, including pre- and post-treatment T1-weighted cases, and a set of morphological and radiomic features for the cases segmented. This data-sharing initiative is expected to enable research into and performance evaluation of automatic BM detection, lesion segmentation, disease status evaluation and treatment planning methods for BMs, as well as the development and validation of predictive and prognostic tools with clinical applicability. [ABSTRACT FROM AUTHOR]

Meningiomas are the most common neoformations of the central nervous system, and represent the 33% of all intracranial neoplasms. The nasosinusal tract is involved in 24% of cases of extracranial localization. The aim of our paper is to present the case of a patient with an ethmoidal sinus meningioma. [ABSTRACT FROM AUTHOR]

Prion diseases, also known as transmissible spongiform encephalopathies, are caused by the accumulation of abnormal isoforms of the prion protein (scrapie isoform of the prion protein, PrPSc) in the central nervous system. Many compounds with anti-prion activities have been found using in silico screening, in vitro models, persistently prion-infected cell models, and prion-infected rodent models. Some of these compounds include several types of polymers. Although the inhibition or removal of PrPSc production is the main target of therapy, the unique features of prions, namely protein aggregation and assembly accompanied by steric structural transformation, may require different strategies for the development of anti-prion drugs than those for conventional therapeutics targeting enzyme inhibition, agonist ligands, or modulation of signaling. In this paper, we first overview the history of the application of polymers to prion disease research. Next, we describe the characteristics of each type of polymer with anti-prion activity. Finally, we discuss the common features of these polymers. Although drug delivery of these polymers to the brain is a challenge, they are useful not only as leads for therapeutic drugs but also as tools to explore the structure of PrPSc and are indispensable for prion disease research. [ABSTRACT FROM AUTHOR]