Nervous System Damage Research Articles

Varicella-zoster virus-related neurological complications: From infection to immunomodulatory therapies.

The Varicella-zoster virus (VZV), classified as a neurotropic member of the Herpesviridae family, exhibits a characteristic pathogenicity, predominantly inducing varicella, commonly known as chickenpox, during the initial infectious phase, and triggering the reactivation of herpes zoster, more commonly recognized as shingles, following its emergence from a latent state. The pathogenesis of VZV-associated neuroinflammation involves a complex interplay between viral replication within sensory ganglia and immune-mediated responses that contribute to tissue damage and dysfunction. Upon primary infection, VZV gains access to sensory ganglia, establishing latent infection within neurons. During reactivation, the virus can spread along sensory nerves, triggering a cascade of inflammatory mediators, chemokines, and immune cell infiltration in the affected neural tissues. The role of both adaptive and innate immune reactions, including the contributions of T and B cells, macrophages, and dendritic cells, in orchestrating the immune-mediated damage in the central nervous system is elucidated. Furthermore, the aberrant activation of the natural defence mechanism, characterised by the dysregulated production of immunomodulatory proteins and chemokines, has been implicated in the pathogenesis of VZV-induced neurological disorders, such as encephalitis, myelitis, and vasculopathy. The intricate balance between protective and detrimental immune responses in the context of VZV infection emphasises the necessity for an exhaustive comprehension of the immunopathogenic mechanisms propelling neuroinflammatory processes. Despite the availability of vaccines and antiviral therapies, VZV-related neurological complications remain a significant concern, particularly in immunocompromised individuals and the elderly. Elucidating these mechanisms might facilitate the emergence of innovative immunomodulatory strategies and targeted therapies aimed at mitigating VZV-induced neuroinflammatory damage and improving clinical outcomes. This comprehensive understanding enhances our grasp of viral pathogenesis and holds promise for pioneering therapeutic strategies designed to mitigate the neurological ramifications of VZV infections.

Effects of Aerobic Training on Sex Hormones in A Cuprizone Rat Model of Multiple Sclerosis.

Central nervous system damage in multiple sclerosis (MS) leads to severe physical disability and neurological defects. Sexual dysfunction and infertility in patients with MS have often been neglected in previous studies. Aerobic exercise is suggested to improve circulating testosterone levels and sexual function. Therefore, the purpose of this study was to investigate the effect of aerobic exercise on sex hormone levels in a cuprizone rat model of MS. In this experimental study, 30 male rats (aged 70 days, 154.55 ± 18.1 g) were randomly divided into five groups: MS, exercise-MS (EX-MS), MS-EX, EX-MS-EX, and normal control (control). MS was induced by feeding cuprizone pellets (0.2%) to the rats for six weeks. The exercise groups performed an aerobic exercise protocol on a treadmill five days/week for six weeks before and during the induction of the MS model. Serum testosterone, follicle stimulating hormone (FSH), and luteinising hormone (LH) levels were measured using the ELISA method with standard kits (ZellBio Germany). Luxol fast blue staining (LFB) of the corpora collosa were performed. The results showed a significant decrease in the serum levels of testosterone, FSH, and LH in the MS groups compared to the control group (P<0.05). There was a significant increase in the serum levels of testosterone, FSH, and LH in the EX-MS-EX, and EX-MS groups compared to the MS group (P<0.05). Aerobic exercise could improve the level of sex hormones in the cuprizone rat model of MS and may be used to attenuate sexual dysfunction in patients with MS.

Discovery of new anti-diabetic potential agents based on paracetamol incorporating sulfa-drugs: Design, synthesis, α-amylase, and α-glucosidase inhibitors with molecular docking simulation

Uncontrolled diabetes can lead to hyperglycemia, which causes neuropathy, heart attacks, retinopathy, and nervous system damage over time, therefore, controlling hyperglycemia using potential drug target inhibitors is a promising strategy. This work focused on synthesizing new derivatives via the diazo group, using a hybridization strategy involving two approved drugs, paracetamol and several sulfonamides. The newly designed diazo-paracetamols 5–12 were fully characterized and then screened for in vitro α-amylase and α-glucosidase activities and exhibited inhibitory percentages (IP) = 92.5–96.5 % and 91.0–95.7 % compared to Acarbose IP = 96.5 and 95.8 %, respectively at 100 μg/mL. The IC50 values of the synthesized derivatives were evaluated against α-amylase and α-glucosidase enzymes, and the results demonstrated moderate to potent activity. Among the tested diazo-paracetamols, compound 11 was found to have the highest potency activity against α-amylase with IC50 value of 0.98 ± 0.015 μM compared to Acarbose IC50 = 0.43 ± 0.009 μM, followed by compound 10 (IC50 = 1.55 ± 0.022 μM) and compound 9 (IC50 = 1.59 ± 0.023 μM). On the other hand, for α-glucosidase, compound 10 with pyrimidine moiety demonstrated the highest inhibitory activity with IC50 = 1.39 ± 0.021 μM relative to Acarbose IC50 = 1.24 ± 0.029 μM and the order of the most active derivatives was 10 >9 (IC50 = 2.95 ± 0.046 μM) >11 (IC50 = 5.13 ± 0.082 μM). SAR analysis confirmed that the presence of 4,5-dimethyl-isoxazole or pyrimidine nucleus attached to the sulfonyl group is important for activity. Finally, the docking simulation was achieved to determine the mode of binding interactions for the most active derivatives in the enzyme's active site.

6-minute walk test in patients hospitalized with COVID-19

Introduction. The 6 Minute Walk Test (6MWT) plays a key role in assessing functional exercise tolerance and prognosis for a wide range of chronic respiratory and cardiovascular diseases. In acute bronchopulmonary diseases, in particular COVID-19, there is practically no data on the possibilities of using 6MWT.Aim. To compare the results of a 6-minute walk test with clinical and laboratory parameters of patients hospitalized with new coronovirus infection.Materials and methods. The prospective, non-randomized comparative study sequentially enrolled 117 patients hospitalized with a confirmed diagnosis of COVID-19. Upon admission to the hospital, all patients performed 6MWT in accordance with international recommendations.Results. During the 6-minute trial, patients walked an average of 390 m (340.0; 420.0). In 96.6% of patients, there was a marked limitation of physical activity. Desaturation during the 6-minute test was registered in 25 (21.4%) patients. When conducting a correlation analysis, it was found that the result of the test with physical activity (the number of meters traveled) is associated with both initial and final SpO2, the presence of desaturation and the severity of dyspnea according to Borg, with the age of patients, the severity of the course of new coronovirus infection, laboratory signs of the activity of the inflammatory process upon admission. Relationships between the results of 6MWT (the number of meters covered and the % decrease in SpO2) and the duration of hospitalization, the maximum volume of lung damage according to CT data, the maximum severity of laboratory signs of inflammation (CRP, ferritin) during hospitalization, the need for oxygen therapy, the volume of anti-inflammatory therapy (doses of systemic glucocorticoids, pulse therapy with methylprednisolone). Patients with desaturation during exercise had a more severe course of the disease with a large amount of lung tissue damage, as well as higher laboratory indicators of the activity of the inflammatory process. It was also found that patients who desaturate during the exercise test more often required oxygen therapy during hospitalization, more often pulse therapy with methylprednisolone was performed.Conclusion. Patients with COVID-19 develop a decrease in physical performance, which is multifactorial. These include respiratory failure due to lung tissue damage, muscle weakness, nervous system damage (anxiety, depression), and systemic inflammation, which characterizes the severity of the infection and the associated immune response. The results of 6MWT may have a certain prognostic value in terms of the severity of the course of the disease, the severity of systemic inflammation, the need for oxygen therapy, and pulse therapy with glucocorticoids.

The role of serum C-Fos and glial fibriller acidic protein levels in detecting the severity of obstructive sleep apnea.

Hypoxia and sleep fragmentations that develop during sleep cause central nervous system damage in patients with obstructive sleep apnea (OSA). This study investigates the relationship between OSA severity and glial fibrillary acidic protein (GFAP) and c-Fos, which are considered indicators of neuronal damage. The study included 84 participants (70 patients with OSA and 14 healthy individuals). All participants were evaluated with the Epworth Sleepiness Scale (ESS) before polysomnography (PSG), and serum GFAP and c-Fos values were measured after PSG. All participants were grouped according to the apnea-hypopnea index (AHI) score (control: AHI < 5, Mild OSA: 5 ≤ AHI < 15; moderate OSA: 15 ≤ AHI < 30; severe OSA: AHI ≥ 30). The average age of the participants was 48.5 ± 11.4 years. According to AHI scoring, 14 healthy individuals (16.7%) were in the control group, and 70 patients (83.3%) were in OSA groups. The serum GFAP levels and c-Fos levels were increased in the OSA groups (7.1 ± 5.7 ng/mL and 7.9 ± 7.5 pg/mL respectively) compared to the control group (1.3 ± 0.4 ng/mL and 2.7 ± 1.4 pg/mL p < 0.001 and p < 0.01, respectively). There was a significant positive correlation between AHI and oxygen desaturation index (ODI) values, which indicate disease severity, and serum c-Fos (r: 0.381 and r:0.931, p < 0.01, respectively) and GFAP (r: 0.793 and r:0.745, p < 0.01, respectively) values. Serum GFAP and c-Fos values, which are considered indicators of neuronal damage, can be used as a serum marker to determine disease severity in OSA.

Impacts of PI3K/protein kinase B pathway activation in reactive astrocytes: from detrimental effects to protective functions.

Astrocytes are the most abundant type of glial cell in the central nervous system. Upon injury and inflammation, astrocytes become reactive and undergo morphological and functional changes. Depending on their phenotypic classification as A1 or A2, reactive astrocytes contribute to both neurotoxic and neuroprotective responses, respectively. However, this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and injuries. Transcriptomic analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles, which emphasizes the heterogeneous nature of their reactivity. Astrocytes actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types, releasing cytokines, and influencing the immune response. The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior, as evidenced by in silico , in vitro , and in vivo results. In astrocytes, inflammatory cues trigger a cascade of molecular events, where nuclear factor-κB serves as a central mediator of the pro-inflammatory responses. Here, we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their activation. We highlight the involvement of various signaling pathways that regulate astrocyte reactivity, including the PI3K/AKT/mammalian target of rapamycin (mTOR), α v β 3 integrin/PI3K/AKT/connexin 43, and Notch/PI3K/AKT pathways. While targeting the inactivation of the PI3K/AKT cellular signaling pathway to control reactive astrocytes and prevent central nervous system damage, evidence suggests that activating this pathway could also yield beneficial outcomes. This dual function of the PI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function modulation. The review emphasizes the importance of employing astrocyte-exclusive models to understand their functions accurately and these models are essential for clarifying astrocyte behavior. The findings should then be validated using in vivo models to ensure real-life relevance. The review also highlights the significance of PI3K/AKT pathway modulation in preventing central nervous system damage, although further studies are required to fully comprehend its role due to varying factors such as different cell types, astrocyte responses to inflammation, and disease contexts. Specific strategies are clearly necessary to address these variables effectively.

Bioinformatics analysis of the potential biomarkers of Multiple Sclerosis and Guillain-Barré syndrome.

Recent research emphasizes the intricate interplay of genetics and epigenetics in neurological disorders, notably Multiple Sclerosis (MS) and Guillain-Barre Syndrome (GBS), both of which exhibit cardiovascular dysregulation, with GBS often featuring serious bradyarrhythmias requiring prompt recognition and treatment. While cardiovascular autonomic dysfunction in MS is typically less severe, orthostatic intolerance affects around half of MS patients. Their distinction lies in their autoimmune responses, MS is an autoimmune disease affecting the central nervous system, causes demyelination and axon damage, leading to cognitive, ocular, and musculoskeletal dysfunction. In contrast, GBS primarily affects the peripheral nervous system, resulting in paralysis and respiratory complications. Despite their differences, both diseases share environmental risk factors such as viral infections and Vitamin D deficiency. This study aims to explore shared gene expression pathways, functional annotations, and molecular pathways between MS and GBS to enhance diagnostics, pathogenesis understanding, and treatment strategies through molecular analysis techniques. Through the gene expression analysis, five significant genes were found UTS2, TNFSF10, GBP1, VCAN, FOS. Results shows that Common DEGs are linked to apoptosis, bacterial infections, and atherosclerosis. Molecular docking analysis suggests Aflatoxin B1 as a potential therapeutic compound due to its high binding affinity with common differentially expressed proteins.

Enhancing regenerative potential: A comprehensive review of stem cell transplantation for sports-related neuronal injuries, with a focus on spinal cord injuries and peripheral nervous system damage

Neuronal injuries, as one of the consequences of sports-related incidents, exert a profound influence on the athletes' future, potentially leading to complete immobility and impeding their athletic pursuits. In cases of severe damage inflicted upon the spinal cord (SC) and peripheral nervous systems (PNS), the regenerative process is notably compromised, rendering it essentially inefficient. Among the pivotal therapeutic approaches for the enhancement and prevention of secondary SC injuries (SCI), stem cell transplantation (SCT) stands out prominently. Stem cells, whether directly involved in replacement and reconstruction or indirectly through modification and secretion of crucial bioenvironmental factors, engage in the intricate process of tissue regeneration. Stem cells, through the secretion of neurotrophic factors (NTFs) (aiming to modulate the immune system), reduction of inflammation, axonal growth stimulation, and myelin formation, endeavor to facilitate the regeneration of damaged SC tissue. The fundamental challenges of this approach encompass the proper selection of suitable stem cell candidates for transplantation and the establishment of an appropriate microenvironment conducive to SC repair. In this article, an attempt has been made to explore sports-related injuries, particularly SCI, to comprehensively review innovative methods for treating SCI, and to address the existing challenges. Additionally, some of the stem cells used in neural injuries and the process of their utilization have been discussed.

Nocturia and obstructive sleep apnoea.

Nocturia, the need to urinate at night, is a common symptom in patients with obstructive sleep apnoea (OSA). Continuous positive airway pressure treatment can reduce nocturia in some patients, but the underlying mechanisms are complex and not fully understood. OSA affects the autonomic nervous system, oxidative stress and endothelial damage. Furthermore, the commonly held theory attributing polyuria to a false signal of cardiac overload and response natriuresis has limitations. A comprehensive approach to the management of nocturia in OSA, considering factors such as comorbidities, medication use, alcohol consumption and lifestyle, is needed. Effective management of nocturia in OSA requires a multidisciplinary approach, and urologists should be aware of the potential effect of OSA on physiology and refer patients for further testing at a sleep centre. In addition to continuous positive airway pressure, other interventions such as oral appliances and surgical obstruction treatment could be beneficial for some patients. Overall, understanding the complex interplay between OSA and nocturia is crucial for optimizing patient outcomes.

Advancements in Cerebrospinal Fluid Biosensors: Bridging the Gap from Early Diagnosis to the Detection of Rare Diseases.

Cerebrospinal fluid (CSF) is a body fluid that can be used for the diagnosis of various diseases. However, CSF collection requires an invasive and painful procedure called a lumbar puncture (LP). This procedure is applied to any patient with a known risk of central nervous system (CNS) damage or neurodegenerative disease, regardless of their age range. Hence, this can be a very painful procedure, especially in infants and elderly patients. On the other hand, the detection of disease biomarkers in CSF makes diagnoses as accurate as possible. This review aims to explore novel electrochemical biosensing platforms that have impacted biomedical science. Biosensors have emerged as techniques to accelerate the detection of known biomarkers in body fluids such as CSF. Biosensors can be designed and modified in various ways and shapes according to their ultimate applications to detect and quantify biomarkers of interest. This process can also significantly influence the detection and diagnosis of CSF. Hence, it is important to understand the role of this technology in the rapidly progressing field of biomedical science.

Post Covid Auto Immune Mediated Encephalopathy by Caspr2 Auto Antibody: The Report of Neurological Division o f “Carlo Poma Civil” Hospital of Mantua

A recent cross sectional study ( Liu, 2021 ) suggests that SARS CoV 2 infection has a potential long term impact on the cognition of patients: we have to face with post covid syndrome and with long covid syndrome, the first characterized by symptoms in regression after an year by infection, the last with persisting symptoms after an year by infection. As the COVID 19 pandemic is still raging in many countries and is expected to last for a long period, the long term cognitive sequelae may bec ome a major publi c health issue long after the pandemic has ended. Longitudinal studies to follow up patients who have recovered from COVID 19 are necessary for better understanding the long term cognitive consequences of COVID 19, particularly among those who have recovered from severe disease. But these are not the unique problems of the so called NEUROCOVID. Neuromuscular manifestations of new coronavirus disease 2019 (COVID‐19) infection are frequent, and include dizziness, headache, myopathy, severe (also axonal) Gui llain Barrè Syndrome and olfactory and gustatory disturbances. Patients with acute central nervous system disorders, such as delirium, impaired consciousness, stroke and convulsive seizures, have a high mortality rate ( Shimohata, 2022 An other severe condition is rappresented by autoimmune encefalopathies COVID related. The encephalitis/encephalopathy that causes consciousness disturbance and seizures can be classified into three conditions, including direct infection with the SARS‐CoV‐2 v irus, encephalopa thy caused by central nervous system damage secondary to systemic hypercytokinemia (cytokine storm) and autoimmune‐mediated encephalitis that occurs after infection.

Extracellular vesicles produced by HIV-1 Nef-expressing cells induce myelin impairment and oligodendrocyte damage in the mouse central nervous system

HIV-associated neurocognitive disorders (HAND) are a spectrum of cognitive impairments that continue to affect approximately half of all HIV-positive individuals despite effective viral suppression through antiretroviral therapy (ART). White matter pathologies have persisted in the ART era, and the degree of white matter damage correlates with the degree of neurocognitive impairment in patients with HAND. The HIV protein Nef has been implicated in HAND pathogenesis, but its effect on white matter damage has not been well characterized. Here, utilizing in vivo, ex vivo, and in vitro methods, we demonstrate that Nef-containing extracellular vesicles (Nef EVs) disrupt myelin sheaths and inflict damage upon oligodendrocytes within the murine central nervous system. Intracranial injection of Nef EVs leads to reduced myelin basic protein (MBP) staining and a decreased number of CC1 + oligodendrocytes in the corpus callosum. Moreover, cerebellar slice cultures treated with Nef EVs exhibit diminished MBP expression and increased presence of unmyelinated axons. Primary mixed brain cultures and enriched oligodendrocyte precursor cell cultures exposed to Nef EVs display a decreased number of O4 + cells, indicative of oligodendrocyte impairment. These findings underscore the potential contribution of Nef EV-mediated damage to oligodendrocytes and myelin maintenance in the pathogenesis of HAND.

Observing astrocyte polarization in brains from mouse chronically infected with Toxoplasma gondii

Toxoplasma gondii (T. gondii) is a protozoan parasite that infects approximately one-third of the global human population, often leading to chronic infection. While acute T. gondii infection can cause neural damage in the central nervous system and result in toxoplasmic encephalitis, the consequences of T. gondii chronic infection (TCI) are generally asymptomatic. However, emerging evidence suggests that TCI may be linked to behavioral changes or mental disorders in hosts. Astrocyte polarization, particularly the A1 subtype associated with neuronal apoptosis, has been identified in various neurodegenerative diseases. Nevertheless, the role of astrocyte polarization in TCI still needs to be better understood. This study aimed to establish a mouse model of chronic TCI and examine the transcription and expression levels of glial fibrillary acidic protein (GFAP), C3, C1q, IL-1α, and TNF-α in the brain tissues of the mice. Quantitative real-time PCR (qRT-PCR), enzyme-linked immunosorbent assay, and Western blotting were employed to assess these levels. Additionally, the expression level of the A1 astrocyte-specific marker C3 was evaluated using indirect fluorescent assay (IFA). In mice with TCI, the transcriptional and expression levels of the inflammatory factors C1q, IL-1α, and TNF-α followed an up-down-up pattern, although they remained elevated compared to the control group. These findings suggest a potential association between astrocyte polarization towards the A1 subtype and synchronized changes in these three inflammatory mediators. Furthermore, immunofluorescence assay (IFA) revealed a significant increase in the A1 astrocytes (GFAP+C3+) proportion in TCI mice. This study provides evidence that TCI can induce astrocyte polarization, a biological process that may be influenced by changes in the levels of three inflammatory factors: C1q, IL-1α, and TNF-α. Additionally, the release of neurotoxic substances by A1 astrocytes may be associated with the development of TCI.

Glymphatic abnormality in systemic lupus erythematosus detected by diffusion tensor image analysis along the perivascular space.

This study aimed to evaluate the activity of the glymphatic system in systemic lupus erythematosus (SLE) by a diffusion-based method termed "Diffusion Tensor Image Analysis aLong the Perivascular Space (DTI-ALPS)", and examined its correlations with morphological changes in the brain. In this cross-sectional study, forty-five female patients with SLE and thirty healthy controls (HCs) were included. Voxel-based and surface-based morphometric analyses were performed to examine T1 weighted images, and diffusion tensor images were acquired to determine diffusivity along the x-, y-, and z-axes in the plane of the lateral ventricle body. The ALPS-index was calculated. The differences in values between SLE patients and HC group were compared using the independent samples t test or Mann-Whitney U test. For the correlations between the ALPS-index and brain morphological parameters, partial correlation analysis and Pearson's correlation analysis were conducted. SLE patients showed lower values for the ALPS-index in left (1.543 ± 0.141 vs 1.713 ± 0.175, p < 0.001), right (1.428 ± 0.142 vs 1.556 ± 0.139, p < 0.001) and whole (1.486 ± 0.121 vs 1.635 ± 0.139, p < 0.001) brain compared with the HC group. The reduced ALPS-index showed significant positive correlations with gray matter loss. The non-invasive ALPS-index could serve as a sensitive and effective neuroimaging biomarker for individually quantifying glymphatic activity in patients with SLE. Glymphatic system abnormality may be involved in the pathophysiologic mechanism underlying central nervous system damage in SLE patients.

Neuron-Specific Enolase-What Are We Measuring?

Since the discovery of the neuron-specific protein by Moore and McGregor in 1965, tens of thousands of studies have investigated the basic and applied significance of neuron-specific enolase (NSE). This promising biomarker, according to many researchers, has not found widespread use in clinical practice, particularly in acute cerebrovascular accidents. Moreover, the several studies refuting the usefulness of serum NSE measurement in critically ill patients leads us to consider the reasons for such contradictory conclusions. In this article, we have analyzed the main directions in the study of NSE and expressed our perspective on the reasons for the contradictory results and the difficulties in implementing the results of these studies in clinical practice. In our opinion, the method of the enzyme-linked immunosorbent assay (ELISA) used in the majority of the studies is inappropriate for the evaluation of NSE as a marker of central nervous system damage, because it does not allow for the differentiation of heterodimers of enolases and the assessment of the enzymatic activity of this group of enzymatic proteins. Therefore, the methodological approach for the evaluation of NSE (γγ-enolase) as a biomarker needs to be elaborated and improved. Furthermore, the specificity of the applied research methods and the appropriateness of the continued use of the term "neuron-specific enolase" must be addressed.

Neurotoxicity of manganese via ferroptosis induced by redox imbalance and iron overload

Manganese (Mn) is an essential trace element for maintaining bodily functions. Excessive exposure to Mn can pose serious health risks to humans and animals, particularly to the nervous system. While Mn has been implicated as a neurotoxin, the exact mechanism of its toxicity remains unclear. Ferroptosis is a form of programmed cell death that results from iron-dependent lipid peroxidation. It plays a role in various physiological and pathological cellular processes and may be closely related to Mn-induced neurotoxicity. However, the mechanism of ferroptosis in Mn-induced neurotoxicity has not been thoroughly investigated. Therefore, this study aims to investigate the role and mechanism of ferroptosis in Mn-induced neurotoxicity. Using bioinformatics, we identified significant changes in genes associated with ferroptosis in Mn-exposed animal and cellular models. We then evaluated the role of ferroptosis in Mn-induced neurotoxicity at both the animal and cellular levels. Our findings suggest that Mn exposure causes weight loss and nervous system damage in mice. In vitro and in vivo experiments have shown that exposure to Mn increases malondialdehyde, reactive oxygen species, and ferrous iron, while decreasing glutathione and adenosine triphosphate. These findings suggest that Mn exposure leads to a significant increase in lipid peroxidation and disrupts iron metabolism, resulting in oxidative stress injury and ferroptosis. Furthermore, we assessed the expression levels of proteins and mRNAs related to ferroptosis, confirming its significant involvement in Mn-induced neurotoxicity.

EVALUATION OF PHYSICAL DEVELOPMENT IN CHILDREN WITH BRONCHIAL ASTHMA

Among the diseases capable of negatively affecting the course of bronchial asthma in children and adolescents, disruptions in nutritional status play an important role, including not only excess body weight and obesity, but also insufficient body weight. Since children with the consequences of perinatal central nervous system damage often exhibit signs of protein-energy deficiency, the aim of the research conducted was to assess the indicators of nutritional status of children with bronchial asthma depending on accompanying neurological symptoms by evaluating the body mass index. 126 children with bronchial asthma were examined, divided into two subgroups: the main group included 65 children (51.6%) with the disease occurring against the background of consequences of perinatal central nervous system damage; the comparison group included 61 patients (48.4%) without accompanying neurological symptoms. The average age of the children was 11.4±2.9 years. According to the results obtained, in 50.8% of observations, children in the main group had insufficient body weight and a decrease in body mass index, while in the comparison group, excess body weight was observed in 37.7% of cases. KEYWORDS: children, bronchial asthma, anthropometry, body mass index, nutritional status, central nervous system

Development of an Infantile GM2 Clinical Rating Scale: Remote Assessment of Clinically Meaningful Health-Related Function.

GM2 gangliosidoses (GM2) are a group of rare lysosomal storage disorders in which accumulation of GM2 gangliosides results in progressive central nervous system damage. The infantile GM2 phenotype is characterized by delays in milestones by 6 months of age, followed by rapid loss of motor, cognitive, and visual function. Advancements in early diagnosis and pharmacotherapies provide promise for improved outcomes. However, the lack of feasible and clinically meaningful clinical outcome assessments for GM2 poses a challenge to characterizing GM2 natural history and selecting clinical trial endpoints. The purpose of this study was to develop a remotely administered infantile GM2 rating scale to measure health-related function in children with infantile GM2. A 2-phase mixed methods design was employed. In phase 1 of the study, 8 families of children with Infantile GM2 completed a natural history survey and a 1:1 semistructured interview to provide caregiver perspectives on the impacts of GM2 on health-related function. In phase 2 of the study, 8 expert clinicians provided feedback via surveys and participated in videoconference-hosted focus groups to refine scale administration and scoring procedures. These methods guided the development of 16 scale items to assess function in 5 health-related function domains: vision, hand and arm use, communication, gross motor, and feeding. This study used caregiver perspectives and expert clinician feedback to develop a remotely administered clinical outcome assessment of clinically meaningful health-related function in children with infantile GM2. Future studies will further evaluate the feasibility, reliability, and validity of the Infantile GM2 Clinical Rating Scale.

Mechanisms by Which SARS-CoV-2 Invades and Damages the Central Nervous System: Apart from the Immune Response and Inflammatory Storm, What Else Do We Know?

Initially reported as pneumonia of unknown origin, COVID-19 is increasingly being recognized for its impact on the nervous system, despite nervous system invasions being extremely rare. As a result, numerous studies have been conducted to elucidate the mechanisms of nervous system damage and propose appropriate coping strategies. This review summarizes the mechanisms by which SARS-CoV-2 invades and damages the central nervous system, with a specific focus on aspects apart from the immune response and inflammatory storm. The latest research findings on these mechanisms are presented, providing new insights for further in-depth research.

Study of Axonal Injury and Degeneration in Drosophila.

A fundamental feature of nervous systems is a highly specified synaptic connectivity between cells and the ability to adaptively change this connectivity through plasticity mechanisms. Plasticity mechanisms are highly relevant for responding to nervous system damage, and studies using nervous system injury paradigms in Drosophila (as well as other model organisms) have revealed conserved molecular pathways that are triggered by axon damage. Simple assays that introduce injuries to axons in either adult flies or larvae have proven to be particularly powerful for uncovering mechanisms of axonal degeneration and clearance. They have also been used to reveal requirements for regrowth of axons and dendrites, as well as signaling pathways that regulate cellular responses to nerve injury. Here we review commonly used and simple to carry out techniques that enable experimenters to study responses to axonal damage in either adult flies (following antennal transection) or larvae (following nerve crush to segmental nerves). Because axons and dendrites in the larval peripheral nervous system can be readily visualized through the translucent cuticle, another versatile method to probe injury responses is to focus high-energy laser light to a small and specific location in the animal. We therefore discuss a method for immobilizing intact larvae for imaging through the cuticle to carry out injury by pulse dye laser, which can be used to generate many different kinds of injuries and directed ablations within intact larvae. These techniques, combined with powerful genetic tools in Drosophila, make the fruit fly an excellent model system for studying the effects of injury and the mechanisms of axon degeneration, synapse plasticity, and immune response.