Disease Of Nervous System Research Articles

Consensus recommendations on multiple sclerosis management in Australia and New Zealand: part 2.

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system with rapidly evolving treatment options and strategies. An iterative modified Delphi process was used to develop 80 consensus recommendations for the management of MS in Australia and New Zealand. Part 1 of these guidelines includes recommendations related to selection of initial disease-modifying therapy (DMT) for MS, assessments before commencing DMT, monitoring disease activity on DMT, switching DMT, and discontinuing DMT. This article, Part 2, covers recommendations related to risk mitigation during treatment with DMT, managing DMT in special situations (including pregnancy, postpartum, breastfeeding, active infection including COVID-19, and malignancy), general lifestyle measures for MS, acute MS relapses, and symptomatic treatments. Together with Part 1, this consensus statement provides practical guidance for clinicians involved in the care of adults (≥ 18 years old) with MS in Australia and New Zealand. A safe, effective and comprehensive approach to managing MS is crucial for improving long term outcomes and quality of life in individuals affected by MS.

Consensus recommendations on multiple sclerosis management in Australia and New Zealand: part 1.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating and degenerative disease of the central nervous system. There were 33 335 people with MS in Australia in 2021 and 2917 in New Zealand in 2006 and the prevalence and incidence are increasing with time. Although new treatments have substantially improved outcomes in recent decades, the treatment landscape has become increasingly complex due to the expanding number of disease-modifying therapies (DMTs) and associated safety considerations. A total of 80 consensus recommendations were developed on the current best-practice management of MS in Australia and New Zealand. Part 1 of these guidelines outlines the consensus recommendations covering domains including DMT counselling and selection, pre-DMT assessments, monitoring disease activity on DMT, switching DMT, and discontinuing DMT. The remaining recommendations are outlined in Part 2, encompassing risk mitigation strategies during treatment with DMT, managing DMT in special situations (including pregnancy, postpartum, breastfeeding, active infection including COVID-19, and malignancy), general lifestyle measures, acute MS relapses, and symptomatic treatments for MS. This two-part position statement provides a practical resource for clinicians on current best-practice consensus recommendations for managing adults (≥ 18 years old) with MS in the Australian and New Zealand health care settings. It outlines the 14 DMTs currently available through the Australian Pharmaceutical Benefits Scheme and eight through the New Zealand Pharmaceutical Schedule, including the unique efficacy, safety and monitoring considerations of each. Through these guidelines, we aim to support safe, timely and effective management of patients with MS in Australia and New Zealand.

Adverse drug event profile of pharmacotherapies for alcohol use disorder: a retrospective pharmacovigilance disproportionality analysis study.

ABSTRACT Background Alcohol Use Disorder (AUD) significantly affects global health, leading to physical deterioration and impacting personal and social relationships. This study aims to evaluate the adverse event profiles (AEP) of three USFDA-approved medications for AUD, acamprosate, disulfiram, and naltrexone, using data from the USFDA Adverse Event Reporting System (AERS). Research designs and methods Reports related to acamprosate, disulfiram, and naltrexone from March 2004 to March 2024 were extracted from the USFDA AERS database. Data were verified, and disproportionality analysis was conducted using frequentist and Bayesian methods. Adverse reactions were assessed based on reporting odds ratio, proportional reporting ratio, and Bayesian measures. Outcomes such as death, life-threatening events, and hospitalization were also analyzed. Results A total of 19,177 unique reports were analyzed (naltrexone: n = 18,544; acamprosate: n = 249; disulfiram: n = 384). Common adverse reactions included hepatobiliary, nervous system, and psychiatric disorders. Disulfiram was associated with coagulopathy and drug interactions, while naltrexone was linked to injection site reactions and hypersensitivity. Naltrexone had higher mortality reports, and disulfiram had more hospitalizations. Conclusion The study underscores the diverse AEPs of these medications, highlighting the need for careful monitoring and individualized treatment to ensure safety and efficacy in managing AUD.

EVALUATION OF THE THERAPEUTIC EFFECTS OF SALVIA ROSMARINUS ESSENTIAL OIL ON NERVOUS SYSTEM DISORDERS

Rosemary (Salvia rosmarinus) is an aromatic plant that has been used for centuries in traditional medicine for its remarkable therapeutic properties. Rosemary contains bioactive compounds with antioxidant, anti-inflammatory, and neuroprotective actions, and it is recognized for its beneficial effects on mental and cognitive health. This review explores the therapeutic potential of rosemary in alleviating nervous system disorders such as Alzheimer's disease (AD), major depressive disorder (MDD), epilepsy, Parkinson's disease (PD), addiction, and attention-deficit hyperactivity disorder (ADHD). Preclinical and clinical research suggests that rosemary extracts, through their active compounds, may enhance cognitive function, protect neurons from oxidative stress, and modulate neurotransmitters involved in cognitive and emotional processes. The findings indicate that rosemary could be a promising complementary therapy in managing nervous system disorders, offering significant benefits for mental and neurological health. However, further studies are needed to fully understand the efficacy and safety of long-term use.

Progression of experimental autoimmune encephalomyelitis in mice and neutrophil-mediated blood-brain barrier dysfunction requires non-muscle myosin light chain kinase.

Blood-brain barrier (BBB) dysfunction occurs in numerous central nervous system disorders. Unfortunately, a limited understanding of the mechanisms governing barrier function hinders the identification and assessment of BBB-targeted therapies. Previously, we found that non-muscle myosin light chain kinase (nmMLCK) negatively regulates the tight junction protein claudin-5 in brain microvascular endothelial cells (BMVECs) under inflammatory conditions. Here, we used complementary animal and primary cell co-culture models to further investigate nmMLCK and claudin-5 during neuroinflammation. We found that nmMLCK-knockout mice resisted experimental autoimmune encephalomyelitis (EAE), including paralysis, demyelination, neutrophil infiltration, and BBB dysfunction. However, transiently silencing claudin-5 culminated in a fulminant disease course. In parallel, we found that neutrophil-secreted factors triggered a biphasic loss in the barrier quality of wild-type BMVEC monolayers, plus pronounced neutrophil migration during the second phase. Conversely, nmMLCK-knockout monolayers resisted barrier dysfunction and neutrophil migration. Lastly, we found an inverse relationship between claudin-5 expression in BMVECs and neutrophil migration. Overall, our findings support a pathogenic role for nmMLCK in BMVECs during EAE that includes BBB dysfunction and neutrophil infiltration, reveal that claudin-5 contributes to the immune barrier properties of BMVECs, and underscore the harmful effects of claudin-5 loss during neuroinflammation.

A Comparison of Vestibular Function in Young Adult Musicians and Nonmusician Peers.

The majority of college-level musicians exceed the daily recommended noise dose level during instrumental practices and performances, although less than one third report wearing hearing protection while playing their instruments. Although the hazardous effects of music on the auditory system have been established, even in young adult musicians still early in their musical careers, the effects of music on the vestibular system are still unclear. The purpose of the present study was to examine vestibular/balance differences between young adult musicians and nonmusicians to determine the effects of music exposure on the vestibular system. Young adult participants aged 18-27 years without any history of hearing loss, vestibular/balance disorder, otologic disorder, or nervous system disorder were included in this study. Participants were divided into musician (n = 19) and nonmusician (n = 18) groups. Vestibular function was assessed and compared via the cervical vestibular evoked myogenic potential (cVEMP), ocular vestibular evoked myogenic potential (oVEMP), video head impulse test (vHIT), and modified clinical test of sensory interaction in balance (mCTSIB). Musicians were found to produce significantly more saccades in the left horizontal semicircular canal during vHIT assessment compared to nonmusicians. Group differences were not found in the cVEMP, oVEMP, or mCTSIB. This study shows the effects of music exposure on the vestibular system in young adult musicians who show early-onset, subclinical findings on the vHIT that could develop into abnormal results on vestibular assessments if hearing protection use is not increased.

Safety profiles of IDH inhibitors: a pharmacovigilance analysis of the FDA Adverse Event Reporting System (FAERS) database

BackgroundWith the increased use of isocitrate dehydrogenase (IDH) inhibitors in acute myeloid leukemia (AML) and cholangiocarcinoma, the toxicity of these drugs is a growing concern. This study aimed to evaluate the adverse events (AEs) of IDH inhibitors based on the Food and Drug Administration Adverse Event Reporting System (FAERS) database.MethodsAE reports for IDH inhibitors (enasidenib, ivosidenib, and olutasidenib) were collected and analyzed from the time of launch through the first quarter of 2024. Only IDH inhibitors reported as the target drug and coded as the primary suspect (PS) were included in the analysis. AEs were standardized and classified according to the preferred term (PT) and system organ classification (SOC) in the Medical Dictionary for Regulatory Activities (MedDRA) version 26.0. Disproportionality analyses including the reporting odds ratio and the Bayesian confidence propagation neural network were performed in data mining to assess IDH inhibitor-relatedAEs. Differentiation syndrome was the AE of special interest.ResultsThe reports number of enasidenib, ivosidenib, and olutasidenib was 11 616 357, 10 067 250, and 2 563 464, respectively. A total of 80 enasidenib-related signals involving 15 SOCs, 78 ivosidenib-related signals involving 17 SOCs, and 7 olutasidenib-related signals involving 4 SOCs were obtained. The most signals reported were “blood and lymphatic system disorders,” “infections and infestations,” and “nervous system disorders” in enasidenib. For signals of ivosidenib, the most frequently reported were “gastrointestinal disorders,” “general disorders and administration site conditions,” and “injury, poisoning and procedural complications.” Ivosidenib was the only IDH inhibitor with signals in “cardiac disorders.” Differentiation syndrome events were reported in 89, 40, and 2 cases for enasidenib, ivosidenib, and olutasidenib, respectively. The median time to onset was 26–31 days for ivosidenib and enasidenib. AML was the most common indication in the differentiation syndrome reports.ConclusionsOur study identifies potential AE signals associated with IDH inhibitors and provides a broader understanding of the safety. The safety profiles highlight the need for long-term safety monitoring of IDH inhibitor recipients. Promptly monitoring and intervention in specific organ systems depending on the type of IDH inhibitor may improve the overall survival or enhance the quality of life. In the future, it will be necessary to validate our findings in prospective large-scale studies and to investigate the underlying mechanisms.

Assessing the inflammation in pediatric MOGAD: Significance of CSF HMGB1 and related biomarkers

Background and purposeMyelin-oligodendrocyte glycoprotein antibody associated disease (MOGAD) is a common inflammatory disease of the central nervous system (CNS) in children that can lead to demyelination. Evaluation and monitoring of biomarkers associated with its pathogenesis would provide vital information on disease progression and therapeutic assessment.MethodsWe assessed NLRP3, HMGB1, IL-6, and IL-33 levels in the cerebrospinal fluid (CSF) of pediatric patients with MOGAD at different time points and their association with the risk of disease. We recruited 30 patients with MOGAD (20 in the acute phase and 10 in remission) and 10 control patients with noninflammatory demyelinating disease. The expanded disability status scale (EDSS) was used to assess disease severity.ResultsNLRP3, HMGB1, and IL-6 levels in the CSF were significantly higher in patients with MOGAD during the acute phase than in remission (P < 0.05, P < 0.05, P < 0.05) and the control group (P < 0.01, P < 0.0001, P < 0.01). HMGB1 levels were significantly correlated with NLRP3 levels (P < 0.01) during the acute phase. Moreover, we found notable correlation between HMGB1 levels and EDSS (P < 0.05) scores. IL-6 levels were significantly correlated with the total number of attacks (P < 0.05), but not with EDSS scores.ConclusionsThese findings suggest that NLRP3, HMGB1, and IL-6 in the CSF may be potential therapeutic targets and are at least partly involved in the pathogenesis of pediatric MOGAD. HMGB1 in the CSF may be a potential biomarker correlating with pediatric MOGAD severity. Further investigations are warranted to validate potential cytokine pathways between that NLRP3, HMGB1, and IL-6 of MOGAD.

Mitochondrial dysfunction, iron accumulation, lipid peroxidation, and inflammasome activation in cellular models derived from patients with multiple sclerosis.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Despite advancements in managing relapsing active illness, effective treatments for the irreversible progressive decline in MS remain limited. Research employing skin fibroblasts obtained from patients with neurological disorders revealed modifications in cellular stress pathways and bioenergetics. However, research using MS patient-derived cellular models is scarce. In this study, we collected fibroblasts from two MS patients to investigate cellular pathological alterations. We observed that MS fibroblasts showed a senescent morphology associated with iron/lipofuscin accumulation and altered expression of iron metabolism proteins. In addition, we found increased lipid peroxidation and downregulation of antioxidant enzymes expression levels in MS fibroblasts. When challenged against erastin, a ferroptosis inducer, MS fibroblasts showed decreased viability, suggesting increased sensitivity to ferroptosis. Furthermore, MS fibroblasts presented alterations in the expression levels of autophagy-related proteins. Interestingly, these alterations were associated with mitochondrial dysfunction and inflammasome activation. These findings were validated in 7 additional patient-derived cell lines. Our findings suggest that the underlying stress phenotype of MS fibroblasts may be disease-specific and recapitulate the main cellular pathological alterations found in the disease such as mitochondrial dysfunction, iron accumulation, lipid peroxidation, inflammasome activation, and pro-inflammatory cytokine production.

Oxazole-Based Ferroptosis Inhibitors with Promising Properties to Treat Central Nervous System Diseases.

Ferroptosis plays an important role in the occurrence and development of many diseases, including neurodegenerative diseases. Thus, ferroptosis inhibitors able to cross the blood-brain barrier may have therapeutic potential. The best ferroptosis inhibitors so far are lipophilic radical trapping antioxidants (RTAs) that block lipid peroxidation in membranes. Several generations of ferrostatins have been synthesized, among which UAMC-3203 showed high potency in animal models with improved properties compared to ferrostatin-1. To further improve its pharmacokinetics properties, drug-likeness, and permeability, we modified UAMC-3203 by decreasing the size of the molecule and reducing its polarity by replacing the sulfonamide first by amide groups and subsequently by isosteric oxazoles. Herein, we present the design, synthesis, and biological evaluation of a novel series of oxazole RTAs with high potency, excellent oral bioavailability, and high concentrations in brain tissue.

Home noninvasive ventilation in pediatric patients: Does one size fit all?

A French national survey showed that 1447 children were treated with long-term continuous positive airway pressure (CPAP) or noninvasive ventilation (NIV) in 2019. Data about the ventilatory settings for children are scarce. The aim of the study was to report the CPAP/NIV settings from the survey according to the patients' age and disorders. CPAP and NIV settings were compared between 5 age groups (<1, 1-5, 6-11, 12-17 and ≥18 years), and 6 disease categories (upper airway disorders; neuromuscular disease, NMD; disorder of the central nervous system; cardiorespiratory disorder; congenital bone disease, CBD; and other). Age correlated positively with constant CPAP pressure (r=0.364, p<.0001), and negatively with CPAP adherence (r=-0.173, p<.0001). Mean age at CPAP initiation, CPAP pressures and adherence did not differ between disorders. Regarding NIV, mean inspiratory positive airway pressure (IPAP) increased with age (r=0.152, p=.0001), whereas respiratory rate (RR; r=-0.593, p<.0001) and adherence to NIV decreased with age (r=-0.154, p=.0002). NIV settings were quite similar between disease categories, with the CBD group having the highest IPAP, and NMD group having the lowest expiratory positive airway pressure and RR. Adherence tended to be higher with NIV than CPAP. CPAP pressure and IPAP increase with age, while settings seem quite similar between diseases. Even if our study provides some information about CPAP/NIV settings, they should always be individually adapted according to the severity of the disease.

A Case-Report on Double Seronegative Neuromyelitis Optica Spectrum Disorder (DN NMOSD)

Neuromyelitis optica spectrum disorder, formerly known as neuromyelitis optica or Devic's disease, affects roughly 0.3 to 4.4 individuals per 100,000. NMOSD is a peculiar inflammatory disease of the central nervous system that manifests clinically as optic neuritis, transverse myelitis, and specific brainstem and brain-inside syndrome. Here we presented a 55-year-old patient who had been normal months prior to developing numbness of the right half of the face and a history of swaying to the right side. He initially received treatment elsewhere with a five-day course of methylprednisolone pulse therapy, resulting in symptom improvement. However, three months later, he experienced a recurrence and came for further management after receiving a second pulse of steroids. The investigations revealed left-sided facial nerve involvement, sensory loss, and impaired joint position sense and vibration sense in the toes, positive Romberg's sign, and gait ataxia. The magnetic resonance imaging showed T2/FLAIR hyperintense lesions, and cerebrospinal fluid analysis supported a possible diagnosis of neuromyelitis optica spectrum disorder. However, the absence of serum Aquaporin-4 and Myelin Oligodendrocyte Glycoprotein antibodies complicates the diagnosis. The patient was treated effectively for the condition with appropriate glycemic control and is under monitoring for recurrence and progression for any modifications in the treatment as needed. This case highlights the complexity of diagnosing the disease, especially in the context of negative antibody tests, and underscores the need for careful differentiation from other central nervous system disorders.

The possible effects of chili peppers on ADHD in relation to the gut microbiota

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, which is characterized by inattention, impulsivity and hyperactivity. Although the etiology and pathogenesis of ADHD are not fully understood, existing studies have shown that it may be related to genetic factors, environmental factors, abnormal brain development, and psychosocial factors. In recent years, with the concept of microbioa-gut-brain axis (MGBA), more and more studies have begun to pay attention to the effect of gut microbiota on ADHD. Dietary structure can significantly change the diversity and abundance of gut microbiota. Therefore, dietary supplements or food additives to regulate gut microbiota have become one of the potential ways to treat ADHD. Peppers, as an important dietary component, have potential value in regulating gut microbiota. Among them, capsaicin (8-methyl N-vanillyl-6-noneamide, CAP), as a key active component of peppers, has been shown to have potential therapeutic effects on central nervous system (CNS) diseases such as Parkinson’s disease, epilepsy, and depression. In addition, much attention has been paid to the beneficial effects of CAP on gut microbiota. Chili peppers contain not only CAP, but also rich in vitamin C and fatty acids, all of which may ameliorate ADHD by modulating the gut microbiota. This finding not only provides a potential treatment for ADHD, but also provides a new perspective to expand the research and clinical treatment of ADHD pathogenesis. Although current research on the potential therapeutic effects of chili peppers on ADHD is still at an early stage and requires further verification through larger-scale and more rigorous controlled studies, its potential clinical value cannot be ignored.

Real-world safety evaluation of brivaracetam: insights from the US FDA Adverse Event Reporting System

ABSTRACT Background Brivaracetam (BRV) is a novel drug for the treatment of epilepsy. This study aimed to detect and characterize adverse events (AEs) associated with BRV from the first quarter of 2016 to the second quarter of 2024 using the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. Research design and methods We utilized disproportionality analysis methods, including the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS), to assess the associations between reported AEs and BRV usage in the FAERS data. Results A total of 1,781 adverse event reports were analyzed, with Brivaracetam as the primary suspected drug. We identified 13 positive system organ classes (SOCs) and 78 positive preferred term signals (PTs), with a particular focus on nervous system disorders, psychiatric disorders, and injury, poisoning, and procedural complications. Exposures related to injury, poisoning, and procedural complications during pregnancy and lactation showed positive signals, including exposure before pregnancy, during breastfeeding, and during pregnancy. These exposures warrant significant attention. Conclusions Based on the FAERS database, we conducted a comprehensive analysis of AEs associated with BRV. This study aims to provide guidance for the clinical application of BRV in epilepsy treatment, thereby improving its safety.

Gastrointestinal autonomic neuropathy in patients with type 2 diabetes mellitus: features of diagnosis and treatment

Diabetes mellitus (DM) type 2 is one of the components of metabolic syndrome. One of the most common complications of type 2 diabetes is diabetic neuropathy, which results in damage to peripheral and/or autonomic nerve fibers. Disorders of the autonomic nervous system - diabetic autonomic neuropathy (DAN)-can occur in up to 60% of patients. One form of GAN is gastrointestinal autonomic neuropathy (GAN). There is no exact information about its prevalence due to the complexity of diagnosis, but according to some data, symptoms occur in half of patients with diabetes. The main manifestations of GAN are esophageal motility disorders (heartburn, reflux), gastroparesis (nausea, vomiting, feeling of fullness), intestinal motility disorders (diarrhea, constipation), anorectal dysfunction (fecal incontinence). Impaired gastrointestinal motility, in particular gastroparesis, leads to changes in the pharmacokinetics of oral glucose-lowering drugs, which reduces their effectiveness. And in patients receiving insulin therapy, impaired movement of food through the gastrointestinal tract can lead to hypoglycemia. In this regard, identifying and treating manifestations of GAN is an important aspect of managing a patient with type 2 diabetes. Diagnosis of GAN should be aimed at excluding other causes of gastrointestinal disorders and includes, depending on the clinical manifestations, fibrogastroduodenoscopy, barium radiography, colonoscopy, etc. The “gold standard” for diagnosing gastroparesis is considered to be measuring gastric emptying using scintigraphy of digested solids, but due to the high cost and complexity of the procedure, this method is not used in routine practice. The main therapeutic measures in the management of patients with diabetes and GAN are glycemic compensation, compliance with nutritional recommendations, treatment of neuropathy and symptomatic therapy.

Recent advances in mesenchymal stem cell therapy for multiple sclerosis: clinical applications and challenges

Multiple sclerosis (MS), a chronic autoimmune disorder of the central nervous system (CNS), is characterized by inflammation, demyelination, and neurodegeneration, leading to diverse clinical manifestations such as fatigue, sensory impairment, and cognitive dysfunction. Current pharmacological treatments primarily target immune modulation but fail to arrest disease progression or entirely reverse CNS damage. Mesenchymal stem cell (MSC) therapy offers a promising alternative, leveraging its immunomodulatory, neuroprotective, and regenerative capabilities. This review provides an in-depth analysis of MSC mechanisms of action, including immune system regulation, promotion of remyelination, and neuroregeneration. It examines preclinical studies and clinical trials evaluating the efficacy, safety, and limitations of MSC therapy in various MS phenotypes. Special attention is given to challenges such as delivery routes, dosing regimens, and integrating MSCs with conventional therapies. By highlighting advancements and ongoing challenges, this review underscores the potential of MSCs to revolutionize MS treatment, paving the way for personalized and combinatory therapeutic approaches.

New Trends in Brain Shuttle Peptides.

The pharmacological treatment of central nervous system diseases faces significant challenges due to the presence of the blood-brain barrier (BBB). This barrier naturally protects the brain and prevents therapeutics from reaching their targets efficiently. However, the BBB allows the passage of nutrients and other molecules that guarantee brain homeostasis through selective transport mechanisms present at the BBB. These mechanisms provide an opportunity for delivering therapeutic agents into the central nervous system using brain shuttles. Here we review the progress of brain shuttle peptide development from 2015 until 2025. We highlight the most utilized peptides and describe trends in strategies to develop new shuttles and enhance their transport efficiency. Additionally, we compared them with other types of brain shuttles and emphasize the progress of peptide shuttles toward clinical translation.

CCL21-CCR7 blockade prevents neuroinflammation and degeneration in Parkinson’s disease models

Parkinson’s disease (PD) is a progressive degenerative disease of the central nervous system associated with neuroinflammation and microglial cell activation. Chemokine signaling regulates neuron-glia communication and triggers a microglial inflammatory profile. Herein, we identified the neuronal chemokine CCL21 as a major cause of microglial cell imbalance through the CCR7 receptor pathway with therapeutic implications for PD. In humans, we found that CCL21 transcript expression was increased in dopaminergic neurons (DANs) of the substantia nigra in PD patients. CCL21 and CCR7 expressions were spatially associated with brain regional vulnerability to synucleinopathies, as well as with the expression of microglial activation, neuroinflammation, and degeneration-related genes. Also, in mouse models of PD, we showed that CCL21 was overexpressed in DANs in vivo and in vitro. Mechanistically, neuronal CCL21 was shown to regulate microglial cell migration, proliferation, and activation in a CCR7-dependent manner through both canonical (PI3K/AKT) and non-canonical (ERK1/2/JNK) signaling pathways. Finally, we demonstrated that navarixin, a clinically relevant chemokine inhibitor with high affinity for the CCR7 receptor, could block CCL21 effects on microglia and prevent neurodegeneration and behavioral deficits in two mouse models of PD induced with either α-synuclein oligomers (αSynO) or 3,4-dihydroxyphenylacetaldehyde (DOPAL). Altogether, our data indicate that navarixin blocks CCL21/CCR7-mediated neuron-microglia communication and could be used as a therapeutic strategy against PD.Graphical

Abstract TP329: Hospital encounters in the 7 days and 30 days before first-ever stroke: An observational study using data linkage

Background/Aim: Up to 20% of people have a hospital encounter in the 30 days before a first ever stroke, suggesting opportunities for better primary prevention. The reasons for these healthcare encounters before stroke have been largely unexplored. We aimed to describe diagnoses in hospital encounters within 7 days and 30 days before a first-ever stroke. Methods: We used a statewide (Tasmania, ~500,000 population) linked dataset comprising emergency department [ED] presentations, hospital admissions and deaths in Australia from 2007-2020. An 8-year look back period was used to identify first ever strokes. ICD 10-AM codes in the principal diagnosis field were used to determine diagnoses in hospital encounters before stroke. We describe the distribution of diagnosis groups for each hospital encounters, separately for ED presentations and hospital admissions, in the 7 days and 30 days before stroke. Results: Out of 4907 first-ever stroke patients, 202 (4.12%) people had 234 hospital admissions within 7 days before stroke and 507 (10.33%) people had 724 hospital admissions within 30 days before stroke. Among 339 (7%) people, there were 351 ED presentations within the 7 days before stroke and among 676 (13.78%) people, there were 765 ED presentations in the 30 days before stroke. In event-level analyses, the most common diagnoses for hospital admissions were dialysis, diseases of circulatory system (e.g. carotid artery stenosis and unruptured cerebral aneurysm), abnormal symptoms or pathological findings (e.g. convulsions and headache), nervous system disorders (e.g. migraine) and respiratory diseases (Table 1). The most common diagnoses for ED presentations were circulatory system disorders, abnormal pathological findings and nervous system disorders in the 7 days and 30 days before stroke. Conclusion: Hospital encounters in the period immediately before stroke are common and associated with a broad range of health conditions. These may represent potentially high-risk groups requiring more intensive primary stroke prevention interventions.

Protective effects of wogonin in the treatment of central nervous system and degenerative diseases.

Wogonin, an O-methylated flavonoid extracted from Scutellaria baicalensis, has demonstrated profound neuroprotective effects in a range of central nervous system (CNS) diseases. This review elucidates the pharmacological mechanisms underlying the protective effects of wogonin in CNS diseases, including ischemic stroke, hemorrhagic stroke, traumatic brain injury, epilepsy, anxiety, neurodegenerative diseases, and CNS infections. Wogonin modulates key signaling pathways, such as the MAPK, NF-κB, and ROS pathways, contributing to its anti-inflammatory, antioxidant, and antiapoptotic properties. In ischemic stroke models, wogonin reduces infarct size and enhances neurological outcomes by mitigating inflammation and oxidative stress. For patients with hemorrhagic stroke and traumatic brain injury, it accelerates hematoma regression, mitigates secondary brain damage, and promotes neurogenesis, making it an entirely new treatment option for patients with limited access to this type of therapy. Its anticonvulsant and anxiolytic effects are mediated through GABA-A receptor modulation. Moreover, wogonin shows promise in treating neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease by promoting autophagy and reducing neuroinflammation. Additionally, it exhibits antiviral properties, offering potential benefits against CNS infections. Despite extensive preclinical evidence, further clinical studies are warranted to confirm its efficacy and safety in humans. This review highlights the great therapeutic potential of wogonin in terms of CNS protection. However, despite the substantial preclinical evidence, further large-scale clinical studies are necessary. Future researchers need to further explore the long-term efficacy and safety of wogonin in clinical trials and translate it for early application in the clinical treatment of true CNS disorders.