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Premature life exposure, meaning an immature central nervous system, presents a significant challenge for the development of postural control and, in turn, overall motor development. Preventing motor delay thus requires identifying, characterizing, and quantifying deficit in postural control as early as possible. In our study, we reviewed the procedures used in past studies to assess postural control among individuals born preterm, specifically the characterization of participants, the instruments and motor tasks involved, the types of data collected and analyzed, and the outcomes. To that end, we performed a literature search on PubMed, Wiley Online Library, Web of Science, and Scopus using Boolean logic and assessed the quality of the studies with a standardized assessment based on the Strengthening the Reporting of Observational Studies in Epidemiology guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. Of 35 potential studies, 24 were included; all evaluated infants born preterm, but six did not include a control group of full-term infants. Although the heterogeneity of measurements, variability of instruments, and divergence in motor tasks examined limit definitive conclusions based on quantitative synthesis and the generalization of the results, most studies revealed dysfunctional postural control among individuals born preterm. [ABSTRACT FROM AUTHOR]

We evaluated the HIV-1 DNA reservoir in peripheral blood mononuclear cells (PBMC) and cerebrospinal fluid (CSF) in people with HIV (PWH) and associations to cognitive dysfunction. Using the intact proviral DNA assay (IPDA), an emerging technique to identify provirus that may be the source of viral rebound, we assessed HIV DNA in CSF and PBMC in PWH regardless of antiretroviral therapy (ART). CSF was used as a sampling surrogate for the central nervous system (CNS) as opposed to tissue. IDPA results (3' defective, 5' defective, and intact HIV DNA) were analyzed by compartment (Wilcoxon signed rank; matched and unmatched pairs). Cognitive performance, measured via a battery of nine neuropsychological (NP) tests, were analyzed for correlation to HIV DNA (Spearman's rho). 11 CSF and 8 PBMC samples from PWH were evaluated both unmatched and matched. Total CSF HIV DNA was detectable in all participants and was significantly higher than in matched PBMCs (p ​= ​0.0039). Intact CSF HIV DNA was detected in 7/11 participants and correlated closely with those in PBMCs but tended to be higher in CSF than in PBMC. CSF HIV DNA did not correlate with global NP performance, but higher values did correlate with worse executive function (p ​= ​0.0440). Intact HIV DNA is frequently present in the CSF of PWH regardless of ART. This further supports the presence of an HIV CNS reservoir and provides a method to study CNS reservoirs during HIV cure studies. Larger studies are needed to evaluate relationships with CNS clinical outcomes.

Proprioception is essential for precise movement as it helps the body transmit important data about its surroundings to the central nervous system for maintaining body posture and position. This study aimed to investigate the effect of direction and joint angle on upper limb proprioception. Thirty individuals (all males) completed a position reproduction activity in 13 directions and three joint angles. It was discovered that upper limb proprioception is dependent on joint angle, direction, and range of motion. The position reproduction error was found to be dependent on the direction, which had a significantly lower accuracy in the direction with a larger range of motion. In addition, upper limb repositioning errors increased at greater limb elevation angles. Our findings also showed that the joint angle did not significantly affect the absolute error of elbow flexion. With an increase in the elbow flexion, the increase of the gravitational moment of the upper arm and hand coupled with the increase of the muscle arm of the biceps brachii possibly causes slight changes in muscle length perceived by spindles or muscular force perceived by Golgi tendon organs. [ABSTRACT FROM AUTHOR]

ImportanceGene editing using clustered regularly interspaced short palindromic repeats (CRISPR) holds the promise to arrest or cure monogenic disease if it can be determined which genetic change to create without inducing unintended cellular dysfunction and how to deliver this technology to the target organ reliably and safely. Clinical trials for blood and liver disorders, for which delivery of CRISPR is not limiting, show promise, yet no trials have begun for central nervous system (CNS) indications.ObservationsThe CNS is arguably the most challenging target given its innate exclusion of large molecules and its defenses against bacterial invasion (from which CRISPR originates). Herein, the types of CRISPR editing (DNA cutting, base editing, and templated repair) and how these are applied to different genetic variants are summarized. The challenges of delivering genome editors to the CNS, including the viral and nonviral delivery vehicles that may ultimately circumvent these challenges, are discussed. Also, ways to minimize the potential in vivo genotoxic effects of genome editors through delivery vehicle design and preclinical off-target testing are considered. The ethical considerations of germline editing, a potential off-target outcome of any gene editing therapy, are explored. The unique regulatory challenges of a human-specific therapy that cannot be derisked solely in animal models are also discussed.Conclusions and relevanceAn understanding of both the potential benefits and challenges of CRISPR gene therapy better informs the scientific, clinical, regulatory, and timeline considerations of developing CRISPR gene therapy for neurologic diseases.

Interindividual variation of human immunodeficiency virus (HIV) RNA setpoint in cerebrospinal fluid (CSF) and its determinants are poorly understood, but relevant for HIV neuropathology, brain reservoirs, viral escape, and reseeding after antiretroviral interruptions. Longitudinal multicentric study on demographic, clinical, and laboratory correlates of CSF HIV RNA in 2000 follow-up visits from 597 people with HIV (PWH) off antiretroviral therapy (ART) and with plasma HIV RNA > the lower limit of quantification (LLQ). Factors associated with CSF control (CSFC; CSF HIV RNA  LLQ) and with CSF/plasma discordance (CSF > plasma HIV RNA > LLQ) were also assessed through mixed-effects models. Posthoc and sensitivity analyses were performed for persistent CSFC and ART-naïve participants, respectively. Over a median follow-up of 2.1 years, CSF HIV RNA was associated with CD4+ and CD8+ T cells, CSF leukocytes, blood-brain barrier (BBB) integrity, biomarkers of iron and lipid metabolism, serum globulins, past exposure to lamivudine, and plasma HIV RNA (model p

Information exchange is essential for the brain, where it communicates the physiological and pathological signals to the periphery and vice versa. Extracellular vesicles (EVs) are a heterogeneous group of membrane-bound cellular informants actively transferring informative calls to and from the brain via lipids, proteins, and nucleic acid cargos. In recent years, EVs have also been widely used to understand brain function, given their "cell-like" properties. On the one hand, the presence of neuron and astrocyte-derived EVs in biological fluids have been exploited as biomarkers to understand the mechanisms and progression of multiple neurological disorders; on the other, EVs have been used in designing targeted therapies due to their potential to cross the blood-brain-barrier (BBB). Despite the expanding literature on EVs in the context of central nervous system (CNS) physiology and related disorders, a comprehensive compilation of the existing knowledge still needs to be made available. In the current review, we provide a detailed insight into the multifaceted role of brain-derived extracellular vesicles (BDEVs) in the intricate regulation of brain physiology. Our focus extends to the significance of these EVs in a spectrum of disorders, including brain tumors, neurodegenerative conditions, neuropsychiatric diseases, autoimmune disorders, and others. Throughout the review, parallels are drawn for using EVs as biomarkers for various disorders, evaluating their utility in early detection and monitoring. Additionally, we discuss the promising prospects of utilizing EVs in targeted therapy while acknowledging the existing limitations and challenges associated with their applications in clinical scenarios. A foundational comprehension of the current state-of-the-art in EV research is essential for informing the design of future studies.

Erdheim-Chester disease (ECD) is an exceedingly rare non-Langerhans cell CD68+ CD1a- S100- histiocytic multi-organ disease. Diagnosis of ECD is often delayed due to non-specific radiographic findings and heterogeneous lesional tissue. Increasingly, the role of genomic alterations is being recognized for both diagnosis and treatment of ECD. More than half of ECD patients harbor the BRAFV600E mutation. Evaluation for this mutation be can falsely negative on immunohistochemical staining and confirmation with molecular analyses is recommended. We present a case of the 44 year-old male with BRAFV600E-positive ECD treated successfully with steroids followed by single-agent dabrafenib.

A cancerous tumor in the brain known as glioblastoma multiforme (GBM) originates from astrocytes of the central nervous system. Consequently, GBM poses significant challenges to the oncology community because of its aggressive characteristics and poor prognosis. GBM hallmarks include fast growth, invasiveness, and high rates of recurrence. This tumor is highly heterogeneous with different genetic and molecular features found within the tumor cells. There is an ongoing obstacle to conceptualizing effective management for this grappling disease. This is largely due to the tumor displaying intra-heterogeneity, in addition to a plethora of differences in the tumor’s microenvironment. The heterogeneity exhibited by this tumor not only makes it more resistant to treatment but also influences its ability to evolve. The Epidermal Growth Factor Receptor (EGFR) which falls under the Human Epidermal Growth Factor (ErbB) family is a transmembrane receptor that assists in understanding complex molecular pathways involved in GBM formation. EGFR mutations have been shown to affect signaling cascades including Ras/Raf/MEK/ERK, PI3K/Akt/mTOR, JAK/STAT, PLC/PKC among others transforming cellular machinery involved in cell survival, proliferation and invasion. Knowledge about EGFR’s aberrant mutations can be useful for developing novel therapeutic strategies aimed at EGFR inhibition in GBM therapy. This gives hope for patients with this challenging disease to have better outcomes.

The relationship between heart failure and diabetes is intricate and bidirectional. Individuals with diabetes face an elevated risk of developing heart failure due to factors like insulin resistance, chronic inflammation, and metabolic irregularities. Elevated blood sugar levels can harm blood vessels and nerves, culminating in the buildup of fatty deposits in arteries, atherosclerosis, and hypertension, which significantly contribute to heart failure. Furthermore, diabetes can adversely impact the structure and function of the heart muscle, impairing its pumping capacity. Conversely, heart failure can also contribute to the onset of diabetes by disrupting the bodys metabolic processes and amplifying insulin resistance. The complex interaction between these conditions mandates a comprehensive approach to managing individuals with both diabetes and heart failure, underscoring the importance of addressing both aspects for enhanced patient outcomes. Although existing pharmacological treatments are limited and frequently associated with undesirable side effects, acupuncture has established itself as a traditional practice with a legacy. It remains a supplementary option for treating cardiovascular diseases. Heart failure and diabetes are both heavily associated with chronic upregulation of the sympathetic nervous system, which has been identified as a pivotal factor in the progression of disease. Mechanistic interplays such as the attenuation of central nitric oxide signaling may interfere with the production or availability of nitric oxide in key areas of the central nervous system, including the brainstem and hypothalamus. This review will delve into the current understanding of acupuncture on the autonomic nervous system and offer insights into its potential role in the future treatment landscape for diabetes and heart failure.

Background: After anterior cruciate ligament reconstruction (ACLR), the risk of recurrence can reach 20%, partially due to poor postural control and impaired sensory processing. Lack of flexibility in proprioceptive postural strategy has recently been shown to be a potential risk factor for ACL injury. Hypothesis/Purpose: This study aimed to compare proprioceptive reweighting and postural control between ACLR and controls elite athletes. It has been hypothesized that athletes with ACLR exhibit impaired proprioceptive reweighting and poor postural control. Study design: Cross-sectional study Methods: Fifty-two ACLR and 23 control elite athletes (50 males and 25 females, mean age 24.7 years) were included. Proprioceptive reweighting was determined using the evolution of proprioceptive weighting (eRPW), calculated from the center of pressure (CoP) displacements generated by tendon vibration during bilateral standing tasks on firm and foam surfaces. An eRPW <95% classified individuals as flexible (i.e., able to reweight proprioceptive signals from the ankle to the lumbar region), whereas an eRPW >105% classified individuals as rigid (i.e., maintaining an ankle dominant strategy). CoP velocity (vCoP) and CoP ellipse area (EA) were used to characterize postural control. Independent sample t-test and a Chi-squared test were used to compare eRPW, vCoP, EA, and the proportion of flexible and rigid athletes between groups. Results: The eRPW was higher in the ACLR group (100.9±58.8 vs. 68.6±26.6%; p=0.031; Rank biserial correlation=0.314; medium), with a greater proportion of rigid athletes than in the control group (38.5 vs. 4.4%; p=0.010), reflecting lower proprioceptive reweighting. The ACLR group had greater EA on foam surface (8.0±4.6 vs. 6.3±4.4cm²; p=0.019), revealing poorer postural control. Conclusion: Elite athletes with ACLR showed impaired proprioceptive reweighting and poor postural control on an unstable surface. This reflects an inability to adapt proprioceptive weighting when balance conditions are changing and suboptimal postural strategies. Level of Evidence: 3b [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) is a severe central nervous system disorder with no currently available effective treatment. Microglia are immune cells in the central nervous system that play crucial roles in the SCI occurrence, development, and recovery stages. They exhibit dynamic polarization over time and can switch between classical activation (M1) and alternative activation (M2) phenotypes to respond to environmental stimuli. The M1 phenotype is involved in initiating and sustaining inflammatory responses, while the M2 phenotype exerts anti-inflammatory effects and promotes tissue repair in damaged areas. Inhibiting M1 polarization and promoting M2 polarization have become hotspots in regulating neuroinflammation and treating SCI. This article provides a comprehensive review centered on modulating microglial polarization phenotypes for SCI treatment. [ABSTRACT FROM AUTHOR]

Phagocytosis is the process by which certain cells or organelles internalise foreign substances by engulfing them and then digesting or disposing of them. Microglia are the main resident phagocytic cells in the brain. It is generally believed that microglia/macrophages play a role in guiding the brain's repair and functional recovery processes. However, the resident and invading immune cells of the central nervous system can also exacerbate tissue damage by stimulating inflammation and engulfing viable neurons. The functional consequences of microglial phagocytosis remain largely unexplored. Overall, phagocytosis is considered a beneficial phenomenon in acute brain injury because it eliminates dead cells and induces an anti-inflammatory response. Osteopontin (OPN) is a phosphorylated glycoprotein induced by injury in various tissues, including brain tissue. In acute brain injuries such as hemorrhagic stroke and ischemic stroke, OPN is generally believed to have anti-inflammatory effects. OPN can promote the reconstruction of the blood-brain barrier and up-regulate the scavenger receptor CD36. But in chronic diseases such as Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS), OPN can cause microglia to engulf neurons and worsen disease progression. We explored the role of OPN in promoting microglial phagocytosis in nervous system disorders. [ABSTRACT FROM AUTHOR]

Background: Central nervous system dysfunction is common in longstanding hereditary transthyretin amyloidosis (ATTRv) caused by the V30M (p.V50M) mutation. Neuropathology studies show leptomeningeal amyloid deposition and cerebral amyloid angiopathy (CAA). Brain MRI is widely used in the assessment of Aβ associated CAA but there are no systematic studies with brain MRI in ATTRv amyloidosis. Methods: we performed 3 T brain MRIs in 16 patients with longstanding (>14 years) ATTRV30M. We additionally retrospectively reviewed 48 brain MRIs from patients followed at our clinic. CNS symptoms and signs were systematically accessed, and MRIs were blindly reviewed for ischaemic and haemorrhagic lesions. Results: in the prospective cohort, we found white matter hyperintensities in 8/16 patients (50%, Fazekas score> =1). There were no relevant microbleeds, large ischaemic or haemorrhagic lesions or superficial siderosis. In the retrospective cohort, microbleeds were found in 5/48 patients (10,4%), two of which with > =20 microbleeds. White matter hyperintensities were found in 20/48 cases (41.7%). White matter lesions, microbleeds and cortical atrophy were not associated with disease duration. Conclusions: white matter hyperintensities are common in ATTRV30M, irrespective of disease duration. Haemorrhagic lesions are rare, even in patients with longstanding disease, suggesting the existence of other risk factors. [ABSTRACT FROM AUTHOR]

Microglia, as immune cells in the central nervous system, possess the ability to adapt morphologically and functionally to their environment. Glymphatic system, the principal waste clearance system in the brain, exhibits circadian rhythms. However, the impact of microglia on the glymphatic system function remains unknown. In this study, we explored the intricate relationship between microglia and the glymphatic system. Examining diurnal patterns, we identified synchronized behaviors in glymphatic activity and microglial morphology, peaking during sleep and exhibiting distinct changes in branching complexity. Depleting microglia using PLX5622 or in P2Y12 knockout mice enhanced glymphatic function. Chemogenetic manipulation of microglia demonstrated that activating HM3D improved glymphatic function, while inhibiting HM4D unexpectedly increased microglial complexity. These findings highlight the dynamic influence of microglia on the glymphatic system. [ABSTRACT FROM AUTHOR]

Purpose: Arterial fenestration involves an artery emerging from the same embryological origin, with its lumen divided into two channels that subsequently rejoin. This kind of vascular variant has consequences, such as focal defects in the histologic layers of the arteries, hemodynamic stress, and challenges for endovascular procedures in the management of vascular pathologies. The main objective of this work is to present a rare vascular variant, a double fenestration of the same P1 segment of a cadaveric specimen, and a literature review of these kind of vascular variants. Methods: A cadaveric study was performed in which 20 central nervous system specimens, from patients without neurological pathology obtained as a donation from the National Institute of Legal Medicine and Forensic Sciences, were dissected for educational and research purposes. Results: In one specimen it was found a double fenestration of the right P1 segment, associated with a single fenestration of the right superior cerebellar artery. Few cases of posterior circulation fenestration, beyond the vertebrobasilar trunk are reported in the literature, with limited understanding of the potential hemodynamic consequences thereof. In all the literature available, only eight cadaveric cases of P1 segment fenestration are documented, often linked with other central nervous system vascular abnormalities such as aneurysms or duplications. Conclusions: There is a single report of unilateral double P1 segment fenestration in a living patient. To our knowledge, this is the second case reported in the literature on this specific anatomical anomaly, and the first such report in a cadaver. [ABSTRACT FROM AUTHOR]

Background: Basal ganglia germ cell tumor (BGGCT) is a rare central nervous system (CNS) tumor. Diffuse hemispheric gliomas, H3 G34-mutant (DHGs) is an invasive glioma involving the cerebral hemispheres. The diagnosis of DHGs depends on the integration of histopathology and molecular pathology. Case report: We reported a patient with an initial diagnosis of BGGCT that was sensitive to subsequent chemoradiotherapy. Unfortunately, a second high-grade glioma was found on magnetic resonance imaging (MRI) six years later. Subsequently, the tumor was completely removed after surgery and the following histopathology plus next generation sequencing (NGS) testing confirmed the diagnosis of DHGs. Interestingly, we found a germline likely pathogenic variant in FANCA. After surgery, the patient received Stupp regimen. The patient had a relapse 13 months after the Stupp regimen and was doing well after surgery. Conclusions: This is the first report of a patient with heterochronous double primary tumor of BGGCT followed by DHGs. [ABSTRACT FROM AUTHOR]

Purpose: Transitional care (TC) is increasingly crucial, particularly in neurosurgery, where optimal follow-through of patients' care is paramount. Challenges of transition are exacerbated by the complexity of neurosurgical conditions, with pediatric and adult neurosurgery often managed separately by different attending neurosurgeons or in different institutions. While numerous models for transitioning have been proposed, several barriers persist, impeding successful transfer from pediatric to adult settings. Our review focuses on important roles neurosurgeons can play in facilitating successful transition, exploring some existing TC models, with emphasis on the benefits of maintaining a single provider. Methods: Clinic visits data between 2019 to 2023 of patients between the ages of 16 to 26 was compiled retrospectively. Successful transition was defined as continued follow-up moving from pediatric to adulthood with lost to follow-up being that of unsuccessful transition. Age, diagnosis and whether patients were successfully transitioned or lost to follow-up were documented. Results: 1829 neurosurgical patients between the ages of 16 to 26 were identified over 5 years. A snapshot review identified 78 adolescent patients deemed to require follow-up into adulthood. 13 patients had epilepsy, 32 central nervous system (CNS) tumors, 17 congenital conditions, 14 neurovascular, and 2 patients had idiopathic intracranial hypertension. All 78 were noted to have successfully transited into their adulthood (age 21 and beyond). Having the same providers; having pediatric and adult neurosurgery within the same institution, was the single most important factor in facilitating successful transition. Conclusion: Neurosurgeons in institutions, particularly those with experience and competencies in both pediatric and adult care, can serve as crucial anchors during the transitional period. At our institution, the implementation of this continuity of care model has demonstrated remarkable success. Institutions with both pediatric and adult services would be uniquely positioned to develop and implement effective transitional care. [ABSTRACT FROM AUTHOR]

Breathlessness is among the most common post-COVID symptoms. In a considerable number of patients, severe breathlessness cannot be explained by peripheral organ impairment. Recent concepts have described how such persistent breathlessness could arise from dysfunctional processing of respiratory information in the brain. In this paper, we present a first quantitative and testable mathematical model of how processing of respiratory-related signals could lead to breathlessness perception. The model is based on recent theories that the brain holds an adaptive and dynamic internal representation of a respiratory state that is based on previous experiences and comprises gas exchange between environment, lung and tissue cells. Perceived breathlessness reflects the brain's estimate of this respiratory state signaling a potentially hazardous disequilibrium in gas exchange. The internal respiratory state evolves from the respiratory state of the last breath, is updated by a sensory measurement of CO2 concentration, and is dependent on the current activity context. To evaluate our model and thus test the assumed mechanism, we used data from an ongoing rebreathing experiment investigating breathlessness in patients with post-COVID without peripheral organ dysfunction (N = 5) and healthy control participants without complaints after COVID-19 (N = 5). Although the observed breathlessness patterns varied extensively between individual participants in the rebreathing experiment, our model shows good performance in replicating these individual, heterogeneous time courses. The model assumes the same underlying processes in the central nervous system in all individuals, i.e., also between patients and healthy control participants, and we hypothesize that differences in breathlessness are explained by different weighting and thus influence of these processes on the final percept. Our model could thus be applied in future studies to provide insight into where in the processing cascade of respiratory signals a deficit is located that leads to (post-COVID) breathlessness. A potential clinical application could be, e.g., the monitoring of effects of pulmonary rehabilitation on respiratory processing in the brain to improve the therapeutic strategies. [ABSTRACT FROM AUTHOR]

There are key differences between the central nervous system (CNS) (brain and spinal cord) and peripheral nervous system (PNS), such as glial cell types, whether there is protection by the blood-brain barrier, modes of synaptic connections, etc. However, there are many more similarities between these two arms of the nervous system, including neuronal structure and function, neuroimmune and neurovascular interactions, and, perhaps most essentially, the balance between neural plasticity (including processes like neuron survival, neurite outgrowth, synapse formation, gliogenesis) and neurodegeneration (neuronal death, peripheral neuropathies like axonopathy and demyelination). This article brings together current research evidence on shared mechanisms of nervous system health and disease between the CNS and PNS, particularly with metabolic diseases like obesity and diabetes. This evidence supports the claim that the two arms of the nervous system are critically linked and that previously understudied conditions of central neurodegeneration or peripheral neurodegeneration may actually be manifesting across the entire nervous system at the same time, through shared genetic and cellular mechanisms. This topic has been critically underexplored due to the research silos between studies of the brain and studies of peripheral nerves and an overemphasis on the brain in neuroscience as a field of study. There are likely shared and linked mechanisms for how neurons stay healthy versus undergo damage and disease among this one nervous system in the body—providing new opportunities for understanding neurological disease etiology and future development of neuroprotective therapeutics. Article Highlights: The central nervous system (CNS) (brain and spinal cord) and peripheral nervous system (PNS) exhibit numerous structural and functional similarities but also key differences. The PNS is relatively understudied compared with the brain. In numerous neurological diseases, symptoms and mechanistic involvement across both the CNS and PNS arms of the nervous system are seen. The PNS provides key bidirectional neural communication between the brain and tissues/organs, including numerous tissues and organs involved in metabolism (adipose, liver, muscle, heart, etc.) The PNS and CNS both undergo neurodegeneration, but peripheral neuropathy is the number one manifestation of neurodegenerative disease in humans. 6361200013112 dbi240004video1 Video 1. Video 1. American Diabetes Association 84th Scientific Sessions: Diabetes Journal Symposium—It Is All in Your Head—Central Nervous System Control of Systemic Metabolism. [ABSTRACT FROM AUTHOR]

Hypothalamic innate immune responses to dietary fats underpin the pathogenesis of obesity, in which microglia play a critical role. Progranulin (PGRN) is an evolutionarily conserved secretory protein containing seven and a half granulin (GRN) motifs. It is cleaved into GRNs by multiple proteases. In the central nervous system, PGRN is highly expressed in microglia. To investigate the role of microglia-derived PGRN in metabolism regulation, we established a mouse model with a microglia-specific deletion of the Grn gene, which encodes PGRN. Mice with microglia-specific Grn depletion displayed diet-dependent metabolic phenotypes. Under normal diet–fed conditions, microglial Grn depletion produced adverse outcomes, such as fasting hyperglycemia and aberrant activation of hypothalamic microglia. However, when fed a high-fat diet (HFD), these mice exhibited beneficial effects, including less obesity, glucose dysregulation, and hypothalamic inflammation. These differing phenotypes appeared to be linked to increased extracellular cleavage of anti-inflammatory PGRN into proinflammatory GRNs in the hypothalamus during overnutrition. In support of this, inhibiting PGRN cleavage attenuated HFD-induced hypothalamic inflammation and obesity progression. Our results suggest that the extracellular cleavage of microglia-derived PGRN plays a significant role in promoting hypothalamic inflammation and obesity during periods of overnutrition. Therefore, therapies that inhibit PGRN cleavage may be beneficial for combating diet-induced obesity. Article Highlights: The mRNA expression of progranulin (PGRN), a precursor protein of granulins (GRNs), increases specifically in hypothalamic microglia during high-fat diet (HFD) feeding. Mice with microglia-specific depletion of the PGRN-encoding gene Grn exhibit fasting hyperglycemia and aberrant activation of hypothalamic microglia under normal diet–fed conditions, whereas they resist the development of obesity, glucose dysregulation, and hypothalamic inflammation under HFD-fed conditions. The enhanced cleavage of anti-inflammatory PGRN into proinflammatory GRNs in the hypothalamus under HFD-fed conditions underlies the diet-dependent metabolic phenotypes of microglial Grn knockout mice. Inhibition of hypothalamic PGRN cleavage attenuates HFD-induced obesity and hypothalamic inflammation. [ABSTRACT FROM AUTHOR]

Purpose: Both cognitive motor dual-tasks (CMDT) protocols and hypoxic environments have been associated with significant impairments in cognitive and physical performance. We aimed to determine the effects of hypoxia on cognitive performance and neuromuscular fatigue during a highly physically demanding CMDT. Methods: Fifteen young adults completed a first session involving a cognitive task (CTLCOG) followed by cycling exercise (CTLEX) in normoxia. After that, they randomly participated in CMDT sessions in normoxia (DTNOR) and hypoxia (DTHYP). The physical exercise consisted of 20 min cycling at a "hard" perceived effort, and the cognitive task consisted of 15 min sustained attention to response time task (SART). Concurrent psycho-physiological measurements included: quadriceps neuromuscular fatigue (peripheral/central components from femoral nerve electrostimulation), prefrontal cortex (PFC) oxygenation by near-infrared spectroscopy, and perception of effort. Results: SART performance significantly decreased in DTNOR (-15.7 ± 15.6%, P < 0.01) and DTHYP (-26.2 ± 16.0%, P < 0.01) compared to CTLCOG (-1.0 ± 17.7%, P = 0.61). Peripheral fatigue similarly increased across conditions, whereas the ability of the central nervous system to activate the working muscles was impaired similarly in DTNOR (-6.1 ± 5.9%, P < 0.001) and DTHYP (-5.4 ± 7.3%, P < 0.001) compared to CTLEX (-1.1 ± 0.2%, P = 0.52). Exercise-induced perception of effort was higher in DTHYP vs. DTNOR and in DTNOR vs. CTLEX. This was correlated with cognitive impairments in both normoxia and hypoxia. PFC deoxygenation was more pronounced in DTHYP compared to DTNOR and CTLEX. Conclusion: In conclusion, performing a sustained attention task together with physically challenging cycling exercise promotes central neuromuscular fatigue and impairs cognitive accuracy; the latter is particularly noticeable when the CMDT is performed in hypoxia. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the current study was to describe the magnitude and pattern of congenital anomalies on routine second‐trimester ultrasound and its practical implication in the management of pregnant women with fetal anomalies at a novice center in East Africa. Methods: This cross‐sectional study was conducted from September 2021 to May 2022 among women who had second‐trimester anatomic scanning. Data were collected using a structured questionnaire and analyzed using SPSS version 23.1. Ethical clearance was obtained from the hospital's institutional review board and informed consent was obtained. Results: The number of congenital anomalies was 45 of 1764 (2.55%). Most (41%) were in the age group 26–30 years and multigravida (62%). Average gestational age at anatomic scanning was 24 weeks. One or more risk factors for congenital anomalies were reported in 19 (31.0%) of the mothers. Most sonographic fetal abnormalities (51.7%) were reported in the central nervous system, followed by renal (18.0%) and skeletal (11.5%). Among the central nervous system anomalies, severe ventriculomegaly was the most common (38.7%), followed by Arnold‐Chiari malformation (19.4%). Thirty‐five (2%) of the mothers had a lethal fetal congenital anomaly and their pregnancy was terminated after counseling and informed consent. Conclusions: The rate of congenital anomalies in this study is comparable with most international data. The introduction of second‐trimester anatomic scanning has led to timely termination of anomalous pregnancies, which contributes to reduction in direct and indirect costs of care and family's psychosocial distress and the stigma associated with the birth of and caring for a child with disability. Synopsis: Routine second‐trimester anatomic scanning at a novice center in East Africa led to early detection of lethal congenital anomalies and timely termination of pregnancies. [ABSTRACT FROM AUTHOR]

The prenatal diagnosis of epignathus presents a unique challenge for physicians. Differential diagnosis is usually based on the anatomic location of the tumor. Typical prenatal ultrasound characteristics of epignathus include a mixed solid and cystic lesion with vascularity in the solid component, originating from the hard or soft palate, and it is often associated with other anomalies such as craniofacial clefts or trans‐sphenoidal intracranial extension. Herein, we present a case of prenatal diagnosis of epignathus with rare ultrasonographic findings, prenatal management requiring collaborative efforts of a multidisciplinary team, and a well‐planned innovative ex utero intrapartum treatment procedure. In addition, this report highlights the evolving postnatal diagnosis of the rare developmental anomaly, duplication of the pituitary gland‐plus syndrome, which includes various midline craniofacial, central nervous system, spinal, and endocrine abnormalities. Synopsis: We report a case of fetal oral epignathus with uncommon ultrasonographic findings managed collaboratively with an innovative EXIT procedure, revealing an associated DPG‐plus syndrome. [ABSTRACT FROM AUTHOR]

This study aims to establish a set of normal values for the objective evaluation of ocular movements using videonystagmography (VNG). Thirty individuals aged between 18 and 50 years, with no history of vestibular symptoms, recurrent headaches, central nervous system (CNS) symptoms, or cochlear symptoms, were selected. The assessment of five types of ocular movements (saccades, pursuit, optokinetic tests, spontaneous nystagmus, and gaze tests) were conducted using VNG. Normal ranges were established for different parameters of saccades, including latency, precision, and velocity in both horizontal and vertical directions for each eye. Pursuit gain was calculated for each eye in all four directions. Optokinetic gain was determined when the stimulation screen moved in all four directions. Symmetric responses were observed in all subjects. No spontaneous nystagmus was observed with fixation, although two participants exhibited nystagmus upon removal of fixation. Gaze tests revealed no abnormalities. [ABSTRACT FROM AUTHOR]

Nanotechnology has significantly impacted human life, particularly in overcoming the limitations associated with neurodegenerative diseases (NDs). Various nanostructures and vehicle systems, such as polymer nanoparticles, carbon nanotubes (CNTs), nanoliposomes, nano-micelles, lipid nanoparticles, lactoferrin, polybutylcyanoacrylate, and poly lactic-co-glycolic acid, have been shown to enhance drug efficacy, reduce side effects, and improve pharmacokinetics. NDs affect millions worldwide and are challenging to treat due to the blood-brain barrier (BBB), which hinders drug delivery to the central nervous system (CNS). Research suggests that natural ingredients can be formulated into nanoparticles, offering a promising approach for ND treatment. This review examines the advantages and disadvantages of herbal-based nanoformulations, highlighting their potential effectiveness when used alone or in combination with other medications. Herbal nanoparticles provide benefits over synthetic ones due to their biocompatibility, reduced toxicity, and potential for synergistic effects. The study's findings can be applied to develop more efficient drug delivery systems, improving the treatment of NDs by enhancing drug penetration across the BBB and targeting affected CNS areas more precisely. [ABSTRACT FROM AUTHOR]

Cryptogenic new‐onset refractory status epilepticus (cNORSE) is a devastating condition with unclear pathogenesis. Here, we analyzed the genetic underprints of 31 cNORSE patients from an autoimmune encephalitis observational cohort through whole‐genome sequencing. Compared to their controls, cNORSE patients exhibited elevated polygenic risk scores (PRS) for traits associated with autoimmune diseases. The individual PRS against these diseases were correlated with specific clinical phenotypes of cNORSE. The variants were enriched in genes expressed in the central nervous system and lymphocytes. These results suggest a shared genetic framework between cNORSE and other autoimmune/autoinflammatory diseases, and its involvement in the disease pathogenesis. ANN NEUROL 2024;96:1201–1208 [ABSTRACT FROM AUTHOR]

Swedish neuroscientist Bror Anders Rexed lived between 1914 and 2002. He was a renowned neuroscientist and a politician who packed a lot into his 88-year life. Bror Rexed is best known for his works on the description of the cytoarchitectonic organization of the cat spinal cord. Rexed laminae as an eponym is a historical landmark for the spinal cord cytoarchitecture. Rexed's name (particularly his surname) has also been linked to the du-reform in Swedish. In this article, we focus on his works on the central and peripheral nervous systems and translational approaches for neurosurgery, as well as his influence on health policies in Sweden. [ABSTRACT FROM AUTHOR]

Introduction: Since the initial identification of Miller Fisher syndrome (MFS) and Bickerstaff brainstem encephalitis (BBE),significant milestones have been achieved in understanding these diseases.Discoveries of common serum antibodies (IgG anti-GQ1b), antecedent infections, neurophysiological data, andneuroimaging suggested a shared autoimmune pathogenetic mechanism rather than distinct pathogenesis, leadingto the hypothesis that both diseases are part of a unified syndrome, termed "Fisher-Bickerstaff syndrome". The subsequent identification of atypical anti-GQ1b-positive forms expanded the classification to a broader condition known as "Anti-GQ1b-Antibody syndrome". Methods: An exhaustive literature review was conducted, analyzing a substantial body of research spanning from the initialdescriptions of the syndrome's components to recent developments in diagnostic classification and researchperspectives. Results: Anti-GQ1b syndrome encompasses a continuous spectrum of conditions defined by a common serological profilewith varying degrees of peripheral (PNS) and central nervous system (CNS) involvement. MFS and BBE represent theopposite ends of this spectrum, with MFS primarily affecting the PNS and BBE predominantly involving the CNS.Recently identified atypical forms, such as acute ophthalmoparesis, acute ataxic neuropathy withoutophthalmoparesis, Guillain-Barré syndrome (GBS) with ophthalmoparesis, MFS-GBS and BBE-GBS overlap syndromes,have broadened this spectrum. Conclusion: This work aims to provide an extensive, detailed, and updated overview of all aspects of the anti-GQ1b syndromewith the intention of serving as a stepping stone for further shaping thereof. Special attention was given to therecently identified atypical forms, underscoring their significance in redefining the boundaries of the syndrome. [ABSTRACT FROM AUTHOR]

Aim: After the relaxation of COVID‐19 mitigation measures, we observed a dramatic increase in pyogenic infections. Based on this observation, we retrospectively analysed all cases of invasive bacterial infections of brain, lung and complicated ear–nose–throat (ENT) infections, in the period from 1 August to 31 March from the years 2018–2019 to 2022–2023. Methods: The study was conducted in two Paediatric Emergency Departments, at IRCCS 'Burlo Garofolo' of Trieste and at Treviso Hospital. Electronic medical records were searched for all cases with a definitive diagnosis at discharge of mastoiditis, suppurative cervical lymphadenitis, retropharyngeal, parapharyngeal and peritonsillar abscess (ENT group), bacterial brain abscesses, epidural empyema, subdural empyema (central nervous system group), thoracic empyema and necrotising pneumonia (lung group). Results: In 2022–2023, we observed an increase in infections compared to the previous years. Total number of cases were 22, 29, 8, 27 and 63 in 2018–2019, 2019–2020, 2020–2021, 2021–2022 and 2022–2023, respectively. The greater increase occurred in thoracic empyema, with a peak incidence of +120% in 2022–2023 in respect of 2021–2022. Conclusion: We reported an important increase in paediatric bacterial complicated infections in two North East Italian regions, possibly correlated with the relaxation of COVID‐19 social distancing measures. [ABSTRACT FROM AUTHOR]

Patients with cancer experience high rates of alterations in mental status. The mechanisms for altered mental status (AMS) in this population are manifold. The cancer itself may cause AMS through direct invasion of the central nervous system or as metastatic leptomeningeal spread. However, cancer patients are also vulnerable to tumor-associated complications such as seizures, cerebral edema, strokes, or cancer treatment-related complications such as infections, direct neural injury from radiation or chemotherapy, edema, or dysregulated autoimmune response from immunotherapies. Both during treatment and as sequelae, patients may suffer neurocognitive complications from chemotherapy and radiation, medications or opportunistic infections, as well as toxic–metabolic, nutritional, and endocrine complications. In this review, we describe a clinical approach to the cancer patient presenting with AMS and discuss the differential drivers of AMS in this patient population. While common etiologies of AMS in noncancer patients (toxic–metabolic or infectious encephalopathy, delirium) are also applicable to cancer patients, we additionally provide a cancer-specific differential diagnosis that warrants special consideration in the cancer patient with AMS. [ABSTRACT FROM AUTHOR]

Summary: A five‐year‐old Dales gelding was presented with an eight‐week history of progressive, apparently nonpainful, cord‐like, subcutaneous masses across the face, neck, trunk and forelimbs. Physical and neurological examinations identified mild, diffuse weakness, hyperaesthesia and moderate tachycardia. Transcutaneous and transrectal ultrasonography and endoscopy of the guttural pouches confirmed marked enlargement of peripheral nerves and visible cranial nerves, respectively. Histopathology of the subcutaneous lesions was indicative of chronic lymphoplasmacytic polyneuritis with fibrosis. The horse failed to respond to treatment with glucocorticoids, showing progressive generalised weakness and was euthanised. Post‐mortem examination identified a generalised lymphadenopathy and widespread dissemination of neoplastic lymphocytes, throughout the peripheral and central nervous system, heart and liver, identified by immunohistochemistry as T‐cell rich B‐cell lymphoma. This is the first report in the veterinary literature of diffuse neurolymphomatosis presenting as visible branching subcutaneous masses. [ABSTRACT FROM AUTHOR]

Neurological disorders are the primary cause of human disability and mortality globally, however, current medications slightly alleviate some symptoms of degenerative diseases. Serine is an important amino acid for the brain function and involved in a variety of biosynthetic pathways and signal transduction processes. The imbalance of serine metabolism is associated with neurodegeneration, including neuroinflammation, oxidative stress and apoptosis. Altered activities of serine metabolizing enzymes and accumulation of serine metabolites affect the survival and function of nerve cells. Abnormal serine levels are observed in animal models with neurological diseases, but not all human studies, therefore, the maintenance of serine homeostasis is a potentially therapeutic strategy for neurological disorders. To date, physiological and pharmacological roles of serine in neurological diseases have not been systemically recapitulated, and the association between serine and neurological diseases is controversial. In this review, we summarize physicochemical properties of serine, biological processes of serine in the brain (source, biotransformation, and transport), and the application of serine in neurological diseases including Alzheimer's disease, schizophrenia, and depression. Here, we highlight physicochemistry, physiology, pharmacology, and therapeutic potentials of serine in the prevention and treatment of neurological dysfunction. Our work provides valuable hints for future investigation that will lead to a comprehensive understanding of serine and its metabolism in cellular physiology and pharmacology. Although broad by necessity, the review helps researchers to understand great potentials of serine in the prevention and treatment of neurological dysfunction. [ABSTRACT FROM AUTHOR]

The mostly aggressive and extremely malignant type of central nervous system is Glioblastoma (GBM), which is characterized by an extremely short average survival time of lesser than 16 months. The primary cause of this phenomenon can be attributed to the extensively altered genome of GBM, which is characterized by the dysregulation of numerous critical signaling pathways and epigenetics regulations associated with proliferation, cellular growth, survival, and apoptosis. In light of this, different genetic alterations in critical signaling pathways and various epigenetics regulation mechanisms are associated with GBM and identified as distinguishing markers. Such GBM prognostic alterations are identified in PI3K/AKT, p53, RTK, RAS, RB, STAT3 and ZIP4 signaling pathways, metabolic pathway (IDH1/2), as well as alterations in epigenetic regulation genes (MGMT, CDKN2A-p16INK4aCDKN2B-p15INK4b). The exploration of innovative diagnostic and therapeutic approaches that specifically target these pathways is utmost importance to enhance the future medication for GBM. This study provides a comprehensive overview of dysregulated epigenetic mechanisms and signaling pathways due to mutations, methylation, and copy number alterations of in critical genes in GBM with prevalence and emphasizing their significance. [ABSTRACT FROM AUTHOR]

Background: Gliomas are highly lethal malignancies that develop in the central nervous system. The primary treatment for gliomas involves surgical resection followed by chemoradiotherapy. However, due to the infiltrative growth nature of gliomas, surgical resection is often incomplete. Moreover, the efficacy of chemotherapeutic drugs is constrained by their ability to cross the blood–brain barrier, and the currently utilized agents can lose effectiveness, particularly with prolonged administration. Lentinan, an active compound in Lentinula edodes, exhibits various pharmacological activities. Purpose: This study aims to investigate the anti-tumor effects of lentinan on glioma U251 cells. Materials and Methods: Cell proliferation assays, cell fluorescence staining, scratch healing experiments, and transwell chamber experiments were conducted to assess the anti-tumor activity of lentinan on U251 cells. Additionally, quantitative real-time polymerase chain reaction (qPCR) and Western blot experiments were performed to validate the anti-tumor mechanism of lentinan. Results: The findings revealed that lentinan significantly suppressed the proliferation of U251 cells, induced robust apoptosis, and decreased the cells' migration and invasion capabilities. Furthermore, lentinan notably influenced the gene and protein expression of p53, Bcl-2, Cyto-c, Bax, Caspases, and MMP-9 in U251 cells. Conclusion: These findings suggest that lentinan may inhibit glioma cells by activating P53 and caspase-related apoptosis pathways. [ABSTRACT FROM AUTHOR]

Population aging is a global reality driven by increased life expectancy. This demographic phenomenon is intrinsically linked to the epidemic of cognitive disorders such as dementia and Alzheimer's disease, posing challenges for elderly and their families. In this context, the search for new therapeutic strategies to prevent or minimize cognitive impairments becomes urgent, as these deficits are primarily associated with oxidative damage and increased neuroinflammation. Ferulic acid (FA), a natural and potent antioxidant compound, is proposed to be nanoencapsulated to target the central nervous system effectively with lower doses and an extended duration of action. Here, we evaluated the effects of the nanoencapsulated FA on d-galactose (d-Gal)- induced memory impairments. Male Wistar adult rats were treated with ferulic acid-loaded nanocapsules (FA-Nc) or non-encapsulated ferulic acid (D-FA) for 8 weeks concurrently with d-Gal (150 mg/kg s.c.) injection. As expected, our findings showed that d-Gal injection impaired memory processes and increased anxiety behavior, whereas FA-Nc treatment ameliorated these behavioral impairments associated with the aging process induced by d-Gal. At the molecular level, nanoencapsulated ferulic acid (FA-Nc) ameliorated the decrease in ACh and glutamate induced by d-galactose (d-Gal), and also increased GABA levels in the dorsal hippocampus, indicating its therapeutic superiority. Additional studies are needed to elucidate the mechanisms underlying our current promising outcomes. Nanoscience applied to pharmacology can reduce drug dosage, thereby minimizing adverse effects while enhancing therapeutic response, particularly in neurodegenerative diseases associated with aging. Therefore, the strategy of brain-targeted drug delivery through nanoencapsulation can be effective in mitigating aging-related factors that may lead to cognitive deficits. [ABSTRACT FROM AUTHOR]

Postoperative delirium (POD) is a common complication in elderly surgical patients, with limited targeted interventions due to incomplete understanding of its pathophysiological mechanisms. Central nervous system (CNS) inflammation, involving glial cell activation, particularly astrocytes, is considered crucial in POD development. Butyrate, a four-carbon fatty acid, has shown protective effects in CNS diseases, but its potential in mitigating POD remains unclear. This study aimed to investigate the impact of sodium butyrate on POD in aged mice. Behavioral tests, including open field, Y maze, and food burying tests, demonstrated that sodium butyrate preconditioning ameliorated laparotomy-induced delirium in aged mice. Pre-treatment with sodium butyrate inhibited astrocyte activation in the hippocampus, reduced interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) expression levels, and protected hippocampal neurons. Furthermore, the study revealed a connection between gut microbiota regulation and central neuroprotective effects mediated by astrocyte activation inhibition. Sodium butyrate improved the intestinal morphological barrier by rebalancing gut microbiota, inhibiting Proteobacteria and Actinobacteria, reducing Allobaculum and Bacteroides abundance, and increasing Oscillospira abundance. This regulation decreased gut permeability, limiting the entry of toxic substances into the bloodstream, thereby reducing inflammation spread and astrocyte overactivation, leading to central anti-inflammatory effects. In conclusion, sodium butyrate may ameliorate POD by inhibiting astrocyte-mediated neuroinflammation through gut microbiota rebalancing. [ABSTRACT FROM AUTHOR]

Neurons are the primary cells responsible for information processing in the central nervous system (CNS). However, they are vulnerable to damage and insult in a variety of neurological disorders. As the most abundant glial cells in the brain, astrocytes provide crucial support to neurons and participate in synapse formation, synaptic transmission, neurotransmitter recycling, regulation of metabolic processes, and the maintenance of the blood-brain barrier integrity. Though astrocytes play a significant role in the manifestation of injury and disease, they do not work in isolation. Cellular interactions between astrocytes and neurons are essential for maintaining the homeostasis of the CNS under both physiological and pathological conditions. In this review, we explore the diverse interactions between astrocytes and neurons under physiological conditions, including the exchange of neurotrophic factors, gliotransmitters, and energy substrates, and different CNS diseases such as Alzheimer's disease, Parkinson's disease, stroke, traumatic brain injury, and multiple sclerosis. This review sheds light on the contribution of astrocyte-neuron crosstalk to the progression of neurological diseases to provide potential therapeutic targets for the treatment of neurological diseases. [ABSTRACT FROM AUTHOR]

Biological mechanisms of exposure to Trihalomethanes (THMs) in swimming pools remain unclear. Investigation of short-term changes in metabolomic profiles due to exposure to THMs during swimming can help to understand the health effects-related mechanisms. With this in view, we aimed to assess exposure of swimmers to THMs in chlorine and ozone-chlorine swimming pools using the metabolomics approach from September 2020 to January 2021 in Tehran. Two parallel panels of 29 healthy adult subjects swam over 60 min in either of swimming pools. Blood samples were collected before and 2 h after swimming to assess metabolomic profile using Hydrogen-Nuclear Magnetic Resonance Spectroscopy (H-NMR). Differential metabolites between the two groups were identified by multivariate analysis methods such as Orthogonal Partial Least-Squares Discriminant Analysis (OPLS-DA) and Random Forest (RF). The levels of THMs in exhaled air as a biomarker of exposure and the metabolic profile as a biomarker of the effect changed significantly between two participants of swimming pools. Based on the significant metabolites, the biochemical pathways were identified by the method of Metabolite Setts Enrichment Analysis (MSEA) and by using the Metaboanalyst platform. The pathways of tryptophan metabolism, galactose metabolism and fructose and mannose metabolism were the most important biochemically significant pathways in individuals after exposure to THMs. Finally, findings from metabolic changes in our study indicate that exposure to THMs in swimming pools can activate the mechanisms of central nervous system disorders, increased uric acid, increased risk of bladder cancer and oxidative stress. [ABSTRACT FROM AUTHOR]

The aim of this review was to evaluate the feasibility of treating sleep disorders using novel gut microbiota intervention strategies. Multiple factors can cause sleep disorders, including an imbalance in the gut microbiota. Studies of the microbiome-gut-brain axis have revealed bidirectional communication between the central nervous system and gut microbes, providing a more comprehensive understanding of mood and behavioral regulatory patterns. Changes in the gut microbiota and its metabolites can stimulate the endocrine, nervous, and immune systems, which regulate the release of neurotransmitters and alter the activity of the central nervous system, ultimately leading to sleep disorders. Here, we review the main factors affecting sleep, discuss possible pathways and molecular mechanisms of the interaction between sleep and the gut microbiota, and compare common gut microbiota intervention strategies aimed at improving sleep physiology. [ABSTRACT FROM AUTHOR]

Studies on the contribution of enteric neuropathy and intestinal homeostasis to central nervous system degeneration using animal models have reported varying results. Recently, colonic myenteric plexus degeneration was observed in trimethyltin-treated rats. Further characterization of this animal model is necessary to determine its potential for investigating the relationship between the enteric nervous system and central nervous system degeneration. In this study, trimethyltin-treated rats (8 mg/kg body weight, i.p.) were used to measure colonic function, structure, and possible colon abnormalities. The colonic function was assessed by measuring fecal pellet output and transit time. Hematoxylin and eosin staining and immunohistochemistry were performed to evaluate inflammatory profiles and intestinal epithelial cell homeostasis. The expression of mRNA encoding tight junction proteins was quantified with quantitative PCR to determine colon permeability. Histological examination of the colon revealed mucosal immune cell infiltration, crypt damage, and high iNOS and arginase-1 expression in the mucosal layer of trimethyltin-treated rats. At the same time, trimethyltin induced high expression of iNOS, arginase-1, and GFAP and increased cell death in the colonic myenteric plexus. The low cell proliferation and low goblet cell distribution suggested altered intestinal epithelial cell homeostasis in trimethyltin-treated rats. Trimethyltin also upregulated claudin 1 expression. However, normal colon function was preserved. In conclusion, the results show that trimethyltin induces colon inflammation and cell death in the colonic myenteric plexus, and disrupts intestinal epithelial cell homeostasis. However, the balance between anti-inflammatory and pro-inflammatory responses maintains normal colon function in trimethyltin-treated rats. [ABSTRACT FROM AUTHOR]

The widely used insecticide chlorpyrifos (CP) is known to inhibit acetylcholinesterase (AChE) activity attributed to result in various neurological disorders and acetylcholine-dependent organ functions including heart, skeletal muscle, lung, gastrointestinal tract, and central nervous systems. Enzyme reactivators, such as oximes, are known to restore AChE activity and mitigate adverse effects. The identification of compounds that reactivate AChE constitute agents with important therapeutic beneficial effects in cases of pesticide poisoning. However, the screening of novel drugs using traditional models may raise ethical concerns. This study aimed to investigate the potential of Drosophila melanogaster as a model organism for screening AChE reactivators, with a focus on organophosphate poisoning. The efficacy of several oximes, including pralidoxime, trimedoxime, obidoxime, methoxime, HI-6, K027, and K048, against CP-induced AChE activity inhibition in D. melanogaster was determined in silico, in vitro, and in vivo experiments. Molecular docking studies indicated a strong interaction between studied oximes and the active-site gorge of AChE. Data showed that selected oximes (100 μM) are effective in the reactivation of AChE inhibited by CP (10 μM) in vitro. Finally, in vivo investigations demonstrated that selected oximes, pralidoxime and K048 (1.5 ppm), reversed the locomotor deficits, inhibition of AChE activity as well as lowered the mortality rates induced by CP (0.75 ppm). Our findings contribute to utilization of D. melanogaster as a robust model for determination of actions of identified new AChE inhibitory agents with more effective therapeutic properties that those currently in use in the clinical practice in treatment of AChE associated disorders. [ABSTRACT FROM AUTHOR]

Hypoxic hypoxia arises from an inadequate oxygen supply to the blood, resulting in reduced arterial oxygen partial pressure and a consequent decline in oxygen diffusion into tissue cells for utilization. This condition is characterized by diminished oxygen content in the blood, while the supply of other nutrients within the blood remains normal. The brain is particularly sensitive to oxygen deficiency, with varying degrees of hypoxic hypoxia resulting in different levels of neural functional disorder. Since the brain has a specific threshold range for the perception of hypoxic hypoxia, mild hypoxic hypoxia can trigger compensatory protective responses in the brain without affecting neural function. These hypoxic compensatory responses enable the maintenance of an adequate oxygen supply and energy substrates for neurons, thereby ensuring normal physiological functions. To further understand the hypoxic compensatory mechanisms of the central nervous system (CNS), this article explores the structural features of the brain's neurovascular unit model, hypoxic signal transduction, and compensatory mechanisms. [ABSTRACT FROM AUTHOR]

Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder characterized by progressive skeletal muscle degeneration and systemic effects, including the central nervous system (CNS). This study aimed to assess the impact of a 14-day ketogenic diet (DCet) on biochemical and clinical parameters in a DMD mouse model. Young adult mice (50 days old) were fed DCet, while control groups received a standard diet. On the 14th day, memory and behavior tests were conducted, followed by biochemical evaluations of oxidative stress, inflammatory biomarkers, body weight, feed intake, and brain-derived neurotrophic factor (BDNF) levels. mdx + DCet mice showed reduced mass (0.2 g ± 2.49) and improved memory retention (p < 0.05) compared to controls. Oxidative damage in muscle tissue and CNS decreased, along with a significant cytokine level reduction (p <0.05). The protocol led to an increase in hippocampal BDNF and mitochondrial respiratory complex activity in muscle tissue and the central nervous system (CNS), while also decreasing creatine kinase activity only in the striatum. Overall, a 14-day DCet showed protective effects by improving spatial learning and memory through reductions in oxidative stress and immune response, as well as increases in BDNF levels, consistent with our study's findings. [ABSTRACT FROM AUTHOR]

Methamphetamine (METH) is a psychostimulant drug widely used because of its arousing, euphoric and hallucinogenic properties. Studies have reported that chronic METH abuse causes neurotoxic effects in the central nervous system (CNS), including alterations in dopaminergic terminals, gray matter atrophy, and microgliosis in different parts of the CNS. METH administration leads to enhancement in extracellular dopamine and serotonin. Moreover, METH increases glutamate release and induces excitotoxicity due to dopamine dysregulation. METH use reduces neuronal survival, damages the physiological functions of neurons and induces neurodegeneration, primarily in association with dopamine dependent mechanisms. Moreover, METH increases protein accumulation and mitochondrial damage in the neuronal cells, and inhibits cellular clearance. Studies have reported the destructive effects of METH on diverse functional structures of the brain. This review describes several interrelated mechanisms including neurochemical changes, apoptosis, autophagy, neuroinflammation and oxidative stress, which have been shown to be involved in METH-induced neural damage. Understanding these mechanisms may pave the way for finding new strategies to prevent, manage and treatment the neurotoxic and neurodegenerative pathways involved in METH-induced disorders. [ABSTRACT FROM AUTHOR]

Mercuric chloride (HgCl2) is extremely toxic to both humans and animals. It could be absorbed via ingestion, inhalation, and skin contact. Exposure to HgCl2 can cause severe health effects, including damages to the gastrointestinal, respiratory, and central nervous systems. The purpose of this work was to explore if carvacrol (CRV) could protect rats lungs from damage caused by HgCl2. Intraperitoneal injections of HgCl2 at a dose of 1.23 mg/kg body weight were given either alone or in conjunction with oral CRV administration at doses of 25 and 50 mg/kg body weight for 7 days. The study included biochemical and histological techniques to examine the lung tissue's oxidative stress, apoptosis, inflammation, and autophagy processes. HgCl2‐induced reductions in GSH levels and antioxidant enzymes (SOD, CAT, and GPx) activity were enhanced by CRV co‐administration. Furthermore, MDA levels were lowered by CRV. The inflammatory mediators NF‐κB, IκB, NLRP3, TNF‐α, IL‐1β, IL6, COX‐2, and iNOS were all reduced by CRV. When exposed to HgCl2, the levels of apoptotic Bax, caspase‐3, Apaf1, p53, caspase‐6, and caspase‐9 increased, but the levels of antiapoptotic Bcl‐2 reduced after CRV treatment. CRV decreased levels of Beclin‐1, LC3A, and LC3B, which in turn decreased HgCl2‐induced autophagy damage. After HgCl2 treatment, higher pathological damage was observed in terms of alveolar septal thickening, congestion, edema, and inflammatory cell infiltration compared to the control group while CRV ameliorated these effects. Consequently, by preventing HgCl2‐induced increases in oxidative stress and the corresponding inflammation, autophagy, apoptosis, and disturbance of tissue integrity in lung tissues, CRV might be seen as a useful therapeutic alternative. [ABSTRACT FROM AUTHOR]

Central nervous system (CNS) tumors are the leading cause of cancer-related death in children. Typical therapy for CNS tumors in children involves a combination of surgery, radiation, and chemotherapy. While upfront therapy is effective for many high-grade tumors, therapy at the time of relapse remains limited. Furthermore, for diffuse intrinsic pontine glioma (DIPG) and diffuse midline glioma (DMG), there are currently no curative therapies. Chimeric antigen receptor T (CAR T) cell therapy is a promising novel treatment avenue for these tumors. Here, we review the preclinical evidence for CAR T cell use in pediatric brain tumors, the preliminary clinical experience of CNS CAR T cell trials, toxicity associated with systemic and locoregional CAR T cell therapy for CNS tumors, challenges in disease response evaluation with CAR T cell therapy, and the knowledge gained from correlative biologic studies from these trials in the pediatric and young adult population. [ABSTRACT FROM AUTHOR]

Given the current increase in mental and neurological disorders, there is an urgent need to develop alternative treatments for patients. Flavonoids exhibit diverse biological activities, including antioxidant, anti-inflammatory and neuroprotective, and has been considered potential therapies for central nervous system diseases, such as Alzheimer's disease, Parkinson's disease, drug addiction, and stroke. Studies have shown that flavonoids protect neurons from oxidative stress, reduce inflammation, improve brain blood flow and enhance cognitive function. Moreover, its modulation of neurotransmission, such as GABAergic, dopaminergic, serotoninergic, and noradrenergic, has been studied for the treatment of mental disorders that require sedative effects, antidepressants, sleep inducers and anxiety reduction. Although more research is needed to fully understand the mechanisms and potential benefits of these compounds, the use of flavonoids for neurological diseases is a promising avenue for future research and development. This review focuses on major flavonoid subclasses and their applications in central nervous system disorders. [ABSTRACT FROM AUTHOR]

Methylmercury (MeHg) is an environmental toxin known to damage the central nervous system. When pregnant women ingest seafood, which may contain accumulated MeHg, fetal development may be affected. The embryonic period, a time of major epigenetic change, is susceptible to epigenetic disruptions due to chemical exposure. Therefore, understanding the molecular mechanism underlying MeHg's effects on neuronal development requires consideration of epigenetic factors. In this study, we investigated epigenetic modifications in the synaptophysin (SYP) and discs large MAGUK scaffold protein 4 (DLG4) genes. LUHMES cells were exposed to 1 nM MeHg for 6 days during days 2–8 of neural differentiation. MeHg exposure significantly reduced the number of spikes observed on day 16 of differentiation. Both mRNA and protein expression levels of SYP and DLG4 were significantly decreased by MeHg exposure. Additionally, MeHg treatment reduced acetyl histone H3 levels associated with transcriptional activity in the SYP gene while increasing histone H3 lysine 27 tri‐methylation (H3K27me3) levels related to transcriptional repression. Conversely, regarding the DLG4 gene, MeHg exposure increased H3K27me3 levels. Differential changes in DNA methylation (high and low methylation states) were observed in the SYP and DLG4 genes due to MeHg exposure depending on CpG site position. In conclusion, this study suggests that epigenetic changes, particularly histone modifications, contribute to decreased MeHg exposure‐induced SYP and DLG4 expression during neuronal differentiation. Epigenetic modifications in synaptophysin (SYP) and discs large MAGUK scaffold protein 4 (DLG4) genes were investigated. LUHMES cells were exposed to 1 nM MeHg for 6 days during days 2–8 of neural differentiation. Both mRNA and protein expression levels of SYP and DLG4 were significantly decreased by MeHg exposure. MeHg exposure increased histone H3 lysine 27 tri‐methylation levels in SYP and DLG4 promoters. In conclusion, epigenetic changes would decrease MeHg exposure‐induced SYP and DLG4 expression during neuronal differentiation. [ABSTRACT FROM AUTHOR]

Purpose: Advancing the development of 7 T MRI for spinal cord imaging is crucial for the enhanced diagnosis and monitoring of various neurodegenerative diseases and traumas. However, a significant challenge at this field strength is the transmit field inhomogeneity. Such inhomogeneity is particularly problematic for imaging the small, deep anatomical structures of the cervical spinal cord, as it can cause uneven signal intensity and elevate the local specific absorption ratio, compromising image quality. This multisite study explores several RF shimming techniques in the cervical spinal cord. Methods: Data were collected from 5 participants between two 7 T sites with a custom 8Tx/20Rx parallel transmission coil. We explored two radiofrequency (RF) shimming approaches from an MRI vendor and four from an open‐source toolbox, showcasing their ability to enhance transmit field and signal homogeneity along the cervical spinal cord. Results: The circularly polarized (CP), coefficient of variation (CoV), and specific absorption rate (SAR) efficiency shim modes showed the highest B1+ efficiency, and the vendor‐based "patient" and "volume" modes showed the lowest B1+ efficiency. The coefficient of variation method produced the highest CSF/spinal cord contrast on T2*‐weighted scans (ratio of 1.27 ± 0.03), and the lowest variation of that contrast along the superior–inferior axis. Conclusion: The study's findings highlight the potential of RF shimming to advance 7 T MRI's clinical utility for central nervous system imaging by enabling more homogenous and efficient spinal cord imaging. Additionally, the research incorporates a reproducible Jupyter Notebook, enhancing the study's transparency and facilitating peer verification. [ABSTRACT FROM AUTHOR]