Severe Neurological Disease Research Articles

Acute transverse myelitis caused by Paragonimus infection: a case report and review of the literature

Acute transverse myelitis (ATM) is a rare but severe neurological disorder that can be triggered by infections, autoimmune conditions, or other factors. While the association between parasitic infections and ATM is uncommon, Paragonimus infection can cause significant neurological damage, posing a diagnostic challenge. We report the case of a 65-year-old male patient who developed acute limb weakness, sensory loss, and fever following abdominal pain. Initial diagnostic tests were inconclusive; however, advanced imaging and metagenomic sequencing of cerebrospinal fluid ultimately confirmed an Paragonimus infection. After treatment with praziquantel, the patient successfully regained substantial motor function. This case highlights the need to consider parasitic infections in endemic areas and demonstrates the critical role of advanced diagnostic tools, such as metagenomic sequencing, in achieving timely diagnosis and treatment, ultimately improving the patient’s prognosis.

An mRNA vaccine provides effective protection against Duck Tembusu Virus infection

As an emerging flavivirus, Duck Tembusu virus (DTMUV) causes severe neurological disorder and acute egg drop syndrome in poultry. Herein, we report the development of a highly effective mRNA vaccine against DTMUV using lipid nanoparticle (LNP) delivery technology. We engineered an mRNA construct encoding the pre-membrane (prM) and envelope (E) proteins of DTMUV, with an upstream signal peptide to enhance secretion. Two doses of our mRNA vaccine elicited robust neutralizing antibody titers and conferred 100% protection against challenge with a prevalent virulent DTMUV strain. Notably, in a head-to-head comparison, the neutralizing antibody titers induced by our mRNA vaccine were approximately 40-fold of a commercial live-attenuated vaccine (FX2010-180P). Importantly, our mRNA vaccine demonstrated efficient maternal antibody transfer via egg yolk deposition, indicating the potential for protecting offspring through maternal immunity. These findings demonstrate the superiority of our mRNA vaccine platform, as well as the feasibility of applying mRNA vaccines in poultry.

Susceptibility of diverse sand fly species to Toscana virus.

Toscana virus (TOSV) is an emerging but neglected human pathogen currently circulating around the Mediterranean basin including North Africa. Human illness ranges from asymptomatic or mild flu-like syndromes to severe neurological diseases such as meningitis or meningoencephalitis. Despite its significant impact, understanding of TOSV transmission and epidemiology remains limited. Sand flies (Diptera: Phlebotominae), specifically Phlebotomus perniciosus and Phlebotomus perfiliewi, are believed to be the primary vectors of TOSV. However, the spread of TOSV to new geographical areas and its detection in other sand fly species suggest that additional species play a role in the circulation and transmission of this virus. This study investigated the vector competence of four sand fly species - P. tobbi, P. sergenti, P. papatasi, and Sergentomyia schwetzi - for two TOSV strains: 1500590 (TOSV A lineage) and MRS20104319501 (TOSV B lineage). Sand flies were orally challenged with TOSV via bloodmeals. None of the tested species showed susceptibility to the TOSV A strain. However, for TOSV B strain, P. tobbi demonstrated a high potential as a new vector, exhibiting high infection and dissemination rates. P. sergenti also showed some susceptibility to TOSV B, with the virus dissemination observed in all infected females. These finding suggests that P. tobbi and P. sergenti are new potential vectors for TOSV B. Given that P. tobbi and P. sergenti are the primary vectors of human leishmaniases in the Balkans, Turkey and Middle East, their susceptibility to TOSV could have significant epidemiological consequences. On the other hand, P. papatasi and S. schwetzi appeared refractory to TOSV B infection. Refractoriness of P. papatasi, a highly anthropophilic species distributed from the Mediterranean to the Middle East and India, suggests that this species does not contribute to TOSV circulation.

Recent Advancements in Neuroimaging-Based Alzheimer's Disease Prediction Using Deep Learning Approaches in e-Health: A Systematic Review.

Alzheimer's disease (AD) is a severe neurological disease that significantly impairs brain function. Timely identification of AD is essential for appropriate treatment and care. This comprehensive review intends to examine current developments in deep learning (DL) approaches with neuroimaging for AD diagnosis, where popular imaging types, reviews well-known online accessible data sets, and describes different algorithms used in DL for the correct initial evaluation of AD are presented. Conventional diagnostic techniques, including medical evaluations and cognitive assessments, usually not identify the initial stages of Alzheimer's. Neuroimaging methods, when integrated with DL techniques, have demonstrated considerable potential in enhancing the diagnosis and categorization of AD. DL models have received significant interest due to their capability to identify AD in its early phases automatically, which reduces the mortality rate and treatment cost of AD. An extensive literature search was performed in leading scientific databases, concentrating on papers published from 2021 to 2025. Research leveraging DL models on different neuroimaging techniques such as magnetic resonance imaging (MRI), positron emission tomography, and functional magnetic resonance imaging (fMRI), and so forth. The review complies with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Current developments show that CNN-based techniques, especially those utilizing hybrid and transfer learning frameworks, outperform conventional DL methods. Research employing the combination of multimodal neuroimaging data has demonstrated enhanced diagnostic precision. Still, challenges such as method interpretability, data heterogeneity, and limited data exist as significant issues. DL has considerably improved the accuracy and reliability of AD diagnosis with neuroimaging. Regardless of issues with data accessibility and adaptability, current studies into the interpretability of models and multimodal fusion provide potential for clinical application. Further research should concentrate on standardized data sets, rigorous validation architectures, and understandable AI methodologies to enhance the effectiveness of DL methods in AD prediction.

Oxidative Stress and Nutritional Antioxidants in Neurological Diseases

A significant number of neurological diseases are pathogenetically related to oxidative stress, including but not limited to cerebrovascular afflictions such as ischemic and hemorrhagic stroke, Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, amyotrophic lateral sclerosis, and so on. Natural nutrients may help limit the impact of oxidative stress and, therefore, delay or prevent the impairment of these diseases. Although these natural components have not entered routine use, many have been studied in preclinical or even clinical settings with promising results. Therefore, the need to find the stage of the research in the field of validating the properties and clinical usefulness of such nutrients represents the main reason this narrative review was conducted. This analysis explored the PubMed database for papers related to the influence of natural nutrients on the onset and evolution of some of the most severe neurological disorders. The results of the review provide an overview of the pathways oxidative stress may undertake and how the use of nutrients may counteract these pathways. In conclusion, natural nutrients may have beneficial effects that can be impactful on clinical outcomes, but more good quality research in this field is needed before formulating any clear recommendation.

Outbreak of Enterovirus D68 in Young Children, Brescia, Italy, August to November 2024.

Enterovirus D68 (EV-D68) is responsible for a plethora of clinical manifestations ranging from asymptomatic infections to severe respiratory symptoms and neurological disorders. EV-D68 was first detected in children with pneumonia in 1962 and, from then, only sporadic cases were reported until 2014, when outbreaks were notified across the world. After the withdrawal of preventive measures against SARS-CoV-2, a significant increase in EV-D68 infections has been reported in 2021-2022. A surveillance program to evaluate the incidence of enterovirus/rhinovirus (EV/RV) infections was implemented at the Brescia Civic Hospital, Italy. Fifty-five EV/RV-positive respiratory samples, belonging to pediatric patients, were subjected to NGS. We observed that 61.8% of samples were positive for EV, with EV-D68 as the most prevalent genotype predominantly detected between August and November 2024. Phylogenetic analysis revealed that EV-D68 sequences formed two monophyletic clades corresponding to the A2 and B3 lineages, highlighting their recent introduction in Italy. Interestingly, 40% of pediatric EV-D68 infections were detected with at least one other EV/RV. Our study highlights the crucial role played by genomic surveillance of respiratory infections to monitor the circulation of emerging and re-emerging viruses, as well as their evolution. This will be fundamental to enable prompt intervention strategies.

Activity-dependent degradation of Kv4.2 contributes to synaptic plasticity and behavior in Angelman syndrome model mice.

Activity-dependent degradation of Kv4.2 contributes to synaptic plasticity and behavior in Angelman syndrome model mice.

The aromatic cure: A scientific review of Nutmeg’s medicinal properties

An aromatic spice sourced from the seeds of a tropical evergreen tree native to the Banda Islands of Indonesia, nutmeg (Myristica fragrans) has been admired for millennia for its cookery and its many therapeutic uses. Nutmeg has long been used in traditional medical systems such as Unani and Ayurveda for severe gastrointestinal and neurological disorders. Modern medical research developments are now supported by scientific evidence for these customary applications. Based on many therapeutic values, including antioxidant, anti-inflammatory, antimicrobial, analgesic, carminative, and neuroprotective, nutmeg has risen as a prospective natural compound. Most of these advantages are ascribed to the many bioactive compounds, including myristicin, elemicin, eugenol, and sabinene, present in it. These plant compounds have been discovered to regulate several biochemical systems, lower oxidative stress, fight microbial infections, and improve cognitive function. The pharmacokinetic and pharmacodynamic properties of the active ingredients of nutmeg are discussed in depth in this review, emphasizing their mechanisms of action and possible medicinal uses. Furthermore, it integrates data from many different types of research, including in vitro studies, animal models, and a small number of clinical trials, to provide a thorough assessment of the therapeutic effectiveness of nutmeg. Moreover, covered are safety issues, dosage concerns, as well as possible toxicities linked with overconsumption. In general, this post tries to link modern science and traditional knowledge, providing an updated and comprehensive view of the medicinal use of nutmeg and its potential as a complementary or substitute therapeutic agent in current medicine.

Identification and Validation of Glycosylation‑Related Genes in Ischemic Stroke Based on Bioinformatics and Machine Learning.

Ischemic stroke (IS) constitutes a severe neurological disorder with restricted treatment alternatives. Recent investigations have disclosed that glycosylation is closely associated with the occurrence and outcome of IS. Nevertheless, data on the transcriptomic dynamics of glycosylation in IS are lacking. The objective of this study was to undertake a comprehensive exploration of glycosylation-related genes (GRGs) in IS via bioinformatics and to assess their immune characteristics. In this study, through the intersection of genes from weighted gene co-expression network analysis, GRGs from five glycosylation pathways, and DEGs from differential expression analysis, 20 candidate GRGs were identified. Subsequently, through LASSO, Random Forest, and SVM-RFE, 3 hub GRGs (F5, PPP6C, and UBE2J1) were identified. Additional, a gene diagnostic model linked to glycosylation was developed and validated. The findings indicated that the diagnostic model could effectively distinguish between IS patients and healthy individuals in the training, validation, and merging datasets, indicating clinical relevance. Subsequently, by employing unsupervised clustering analysis, IS patients were classified into three clusters, and significant disparities were witnessed in immune cell infiltration among distinct clusters. In summary, this study successfully identified hub GRGs in IS and investigated the roles of these hub genes in the immune microenvironment, indicating potential clinical applications for IS.

A mix-and-match reverse genetics system for evaluating genetic determinants of orthobunyavirus neurological disease.

The encephalitic orthobunyaviruses have tri-segmented, negative sense RNA genomes and can cause severe neurological disease in humans, including La Crosse virus (LACV), which is the leading cause of pediatric arboviral encephalitis in the United States. However, little is known about the genetic factors that drive neuropathogenesis. Reverse genetics systems (RGS) are valuable tools for studying viral genetics and pathogenesis. Plasmid-based cDNA reverse genetics systems are available for LACV, however the plasmid backbones are medium-copy number and have a propensity for recombination. We therefore generated a plasmid-based cDNA reverse genetics system for LACV utilizing a more stable and high-copy number plasmid backbone. Additionally, we created the first full reverse genetics systems for two closely related orthobunyaviruses, Jamestown Canyon virus (JCV), and Inkoo virus (INKV), which have differing reported disease incidences in humans and differing neuropathogenic phenotypes in mice compared to LACV. We compared wild type (wt) viruses with RGS-derived wt viruses in human neuronal cells and in mice, and found that RGS-derived wt viruses maintained the replication and neuropathogenic phenotypes of their wt counterpart. Additionally, we demonstrated that reverse genetics plasmids from different parental viruses can be readily mixed-and-matched to generate reassortant viruses. This system provides a valuable genetic tool utilizing viruses with differing neuropathogenic phenotypes to investigate the genetic determinants of orthobunyavirus neuropathogenesis.

Improved Alzheimer Disease Diagnosis With a Machine Learning Approach and Neuroimaging: Case Study Development.

Alzheimer disease (AD) is a severe neurological brain disorder. While not curable, earlier detection can help improve symptoms substantially. Machine learning (ML) models are popular and well suited for medical image processing tasks such as computer-aided diagnosis. These techniques can improve the process for an accurate diagnosis of AD. In this paper, a complete computer-aided diagnosis system for the diagnosis of AD has been presented. We investigate the performance of some of the most used ML techniques for AD detection and classification using neuroimages from the Open Access Series of Imaging Studies (OASIS) and Alzheimer's Disease Neuroimaging Initiative (ADNI) datasets. The system uses artificial neural networks (ANNs) and support vector machines (SVMs) as classifiers, and dimensionality reduction techniques as feature extractors. To retrieve features from the neuroimages, we used principal component analysis (PCA), linear discriminant analysis, and t-distributed stochastic neighbor embedding. These features are fed into feedforward neural networks (FFNNs) and SVM-based ML classifiers. Furthermore, we applied the vision transformer (ViT)-based ANNs in conjunction with data augmentation to distinguish patients with AD from healthy controls. Experiments were performed on magnetic resonance imaging and positron emission tomography scans. The OASIS dataset included a total of 300 patients, while the ADNI dataset included 231 patients. For OASIS, 90 (30%) patients were healthy and 210 (70%) were severely impaired by AD. Likewise for the ADNI database, a total of 149 (64.5%) patients with AD were detected and 82 (35.5%) patients were used as healthy controls. An important difference was established between healthy patients and patients with AD (P=.02). We examined the effectiveness of the three feature extractors and classifiers using 5-fold cross-validation and confusion matrix-based standard classification metrics, namely, accuracy, sensitivity, specificity, precision, F1-score, and area under the receiver operating characteristic curve (AUROC). Compared with the state-of-the-art performing methods, the success rate was satisfactory for all the created ML models, but SVM and FFNN performed best with the PCA extractor, while the ViT classifier performed best with more data. The data augmentation/ViT approach worked better overall, achieving accuracies of 93.2% (sensitivity=87.2, specificity=90.5, precision=87.6, F1-score=88.7, and AUROC=92) for OASIS and 90.4% (sensitivity=85.4, specificity=88.6, precision=86.9, F1-score=88, and AUROC=90) for ADNI. Effective ML models using neuroimaging data could help physicians working on AD diagnosis and will assist them in prescribing timely treatment to patients with AD. Good results were obtained on the OASIS and ADNI datasets with all the proposed classifiers, namely, SVM, FFNN, and ViTs. However, the results show that the ViT model is much better at predicting AD than the other models when a sufficient amount of data are available to perform the training. This highlights that the data augmentation process could impact the overall performance of the ViT model.

Drug-induced Guillain-Barré Syndrome: a disproportionality analysis based on the US FDA adverse event reporting system

ABSTRACT Background Guillain-Barré Syndrome (GBS) is a rare but severe neurological disorder often precipitated by infections, vaccines, and potentially by certain medications. Drug-induced GBS, though less commonly reported, presents significant diagnostic and therapeutic challenges. This study investigates the correlation between various medications and the onset of GBS. Research design and methods We conducted a retrospective pharmacovigilance analysis using data from the FDA Adverse Event Reporting System (FAERS) from Q1 2004 to Q1 2024. The analysis focused on identifying drugs frequently associated with GBS and examining the time-to-onset and severity of these events. Results From over 17 million adverse events, 1,869 cases were identified as drug-induced GBS. Monoclonal antibodies and immunomodulators were the most frequently implicated drug classes. The median time-to-onset for GBS was within the first 30 days following drug exposure. Approximately 51.8% of the cases resulted in severe outcomes, such as hospitalization or disability. Drugs such as brentuximab vedotin and efalizumab showed strong associations with GBS occurrences. Conclusions This study highlights the importance of monitoring for GBS symptoms following the administration of certain medications, particularly those that affect immune function, and underscores the need for healthcare providers to be aware of the potential neurological risks associated with these medications.

Molecular mechanisms of interaction between ferroptosis and cuproptosis in ischemic stroke. Pharmacological perspectives on preventing brain dysfunction

Ischemic stroke is one of the most severe and common neurological disorders, posing a significant threat to the health and life expectancy of affected individuals. Resulting from impaired blood flow, ischemic stroke leads to hypoxia and cerebral tissue ischemia, triggering a cascade of pathophysiological changes that markedly exacerbate neuronal damage and may ultimately result in cell death. New recent studies increasingly focus on newly discovered mechanisms of cell death, such as ferroptosis and cuproptosis. There is growing evidence supporting the independent roles of ferroptosis and cuproptosis in ischemic stroke. The aim of this review is to elucidate the potential mechanisms of cross-regulation between ferroptosis and cuproptosis and to investigate their regulatory roles in ischemic stroke. This review thoroughly examines intracellular interactions between ferroptosis and cuproptosis in ischemic stroke, emphasizing key aspects such as the fundamental roles of iron and copper, metabolic disturbances in ischemic stroke, cross-influences, and signaling pathways. Summarizing recent publications not only deepens our understanding of the pathogenesis of ischemic stroke but also suggests novel perspectives and directions for future pharmacological interventions in the treatment of ischemic stroke.

Exosome-shuttled miR-5121 from A2 astrocytes promotes BSCB repair after traumatic SCI by activating autophagy in vascular endothelial cells

Spinal cord injury (SCI) is a severe neurological disorder that significantly impacts patients’ quality of life. Following SCI, the blood-spinal cord barrier (BSCB) is destroyed, leading to ischemia and hypoxia, which further exacerbates the imbalance in the spinal cord microenvironment. A2-type astrocytes, which arise under ischemic and hypoxic conditions, have been reported to promote SCI repair. However, the roles of exosomes derived from A2 astrocytes (A2-Exos) in SCI have not been explored. This study aims to investigate the role of A2-Exos in SCI repair, particularly in BSCB restoration, and to elucidate its potential mechanisms. GEO database analysis, western blotting, and immunofluorescence were used to detect A2 astrocyte polarization after SCI in mice. In vitro, A2 astrocytes were obtained through hypoxia induction, and A2-Exos were extracted via ultracentrifugation. An in vivo SCI model and a series of in vitro experiments demonstrated the reparative effects of A2-Exos on BSCB following SCI. Furthermore, miRNA sequencing analysis and rescue experiments confirmed the role of miRNAs in A2-Exos-mediated BSCB repair. Finally, luciferase assays and western blotting were performed to investigate the underlying mechanisms. The results showed that A2-Exos promote motor function recovery and BSCB repair in mice following SCI. In vitro, A2-Exos facilitated BSCB reconstruction and endothelial cell autophagy. miRNA sequencing identified miR-5121 as the most significantly enriched miRNA in A2-Exos, suggesting its involvement in BSCB repair and autophagy regulation. AKT2 was identified as a potential downstream target of miR-5121. Functional gain- and loss-of-function experiments further validated the miR-5121/AKT2 axis. Finally, we demonstrated that the AKT2/mTOR/p70S6K pathway may mediate the effects of miR-5121 in A2-Exos on BSCB repair.

Parechovirus: neglected for too long?

Parechoviruses are non-enveloped, positive-sense, single-stranded RNA viruses that have been isolated from multiple vertebrate species. Infection with these etiologic agents of typically mild childhood respiratory and gastrointestinal illness in humans is nearly universal, and a subset of infected neonates and infants develop severe neurologic diseases. Rodent parechoviruses cause myocarditis, encephalitis, and perinatal death in multiple rodent species. The key steps of the viral life cycle, clinical characteristics, and global burden of these viruses are not well characterized yet, particularly for nonhuman parechoviruses. Here, we review the history of human and nonhuman parechovirus isolation, global seroprevalence and distribution, viral biology, and evolution, considering these factors might contribute to host specificity, virulence, tissue tropism, pathogenesis, host immunity, and population dynamics.

Psychological aspects of hippotherapy for children with severe neurological impairment: An exploratory study.

Neuropediatric hospitalization presents significant psychological challenges that affect quality of life, learning, and treatment adherence. Hippotherapy might address these factors, but its psychological effects are underexplored. This paper explores the psychological and neuropsychological potential of hippotherapy in pediatric neurorehabilitation. Objectives include analyzing (1) patient characteristics, (2) session characteristics, (3) patients' psychological and neuropsychological reactions, and (4) therapists' perceptions of the extent to which the therapeutic goals were realized in the sessions. This retrospective explorative study examines data from 581 children and adolescents (M = 9.01 years, SD = 3.88) with severe neurological disorders who underwent hippotherapy. We used the registration form for each patient and session-documentation forms for each hippotherapy session. We extracted information regarding patient and session characteristics, performed a content analysis on the documented reactions of the patients and the predefined neuropsychosocial goals set by the rehabilitation team, and examined to what extent the goals were met during hippotherapy. The data were analyzed using descriptive statistics. Patients received an average of 3.47 hippotherapy sessions. During hippotherapy, 66.4% of the predefined goals were reached; cognitive functions and social behavior were the most successfully achieved goals. The most frequently documented patient reaction was had fun (81% of all sessions). Our study shows that hippotherapy is a feasible and beneficial treatment for neuropediatric patients with severe neurological impairments. The goals of hippotherapy can be much broader than the usually targeted physical functioning and mobility. Hippotherapy might be especially effective in promoting fun and motivation and in addressing patients' socioemotional needs.

Soy Isoflavones Protects Against Stroke by Inhibiting Keap1/NQO1/Nrf2/HO-1 Signaling Pathway: Network Pharmacology Analysis Combined with the Experimental Validation.

Objectives: Ischemic stroke is a severe neurological disorder with high morbidity, mortality, and disability rates, posing a substantial burden on patients, families, and healthcare systems. Soy isoflavone (SI), a naturally occurring phytoestrogen, has demonstrated promising neuroprotective effects. This study aimed to evaluate the anti-stroke efficacy of SI and elucidate its underlying mechanisms through integrated phytochemical profiling, network pharmacology, and both in vitro and in vivo experimental validation. Methods: Active constituents of SI were extracted via reflux and identified using liquid chromatography-mass spectrometry (LC-MS). Network pharmacology was employed to predict therapeutic targets and signaling pathways. The neuroprotective effects of SI were first assessed in PC12 cells subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) injury in vitro. For in vivo evaluation, transient cerebral ischemia-reperfusion injury was induced using the bilateral common carotid artery occlusion (BCCAO) model in adult male ICR rats (27.3 ± 1.8 g; 6-8 weeks old), obtained from the Shanghai Experimental Animal Center, Chinese Academy of Sciences. Forty-eight rats were randomly assigned into four groups (n = 12): sham, model (BCCAO), SI-treated (100 mg/kg, oral gavage for 5 days), and edaravone (EDA)-treated (10 mg/kg, i.p., positive control). All procedures were approved by the Institutional Animal Care and Use Committee of Changchun Normal University (Approval No. 2024003, 13 March 2024) and conducted in accordance with the NIH guidelines and ARRIVE 2.0 reporting standards. Results: In vitro, SI significantly enhanced PC12 cell viability from 57.23 ± 2.88% to 80.76 ± 4.43% following OGD/R. It also reduced intracellular Ca2+ by 58.42%, lactate dehydrogenase (LDH) release by 37.67%, caspase-3 activity by 55.05%, and reactive oxygen species (ROS) levels by 74.13% (p < 0.05). A flow cytometry analysis revealed that OGD/R increased the apoptosis rate from 5.34% (control) to 30.85% (model group), which was significantly attenuated by SI treatment, especially in the 560 µg/mL group (20.00%), followed by the 140 and 280 µg/mL groups. In vivo, SI improved neurological scores from 8.3 ± 1.09 to 6.8 ± 1.68, reduced cerebral infarction volume by 18.49%, and alleviated brain edema by 10.42% (p < 0.05). SI also decreased malondialdehyde (MDA) and LDH levels by 31.15% and 39.46%, respectively, while increasing the activity of antioxidant enzymes: superoxide dismutase (SOD) by 11.70%, catalase (CAT) by 26.09%, and glutathione peroxidase (GSH-px) by 27.55% (p < 0.01). Scratch assay results showed that SI restored the impaired migratory ability of the OGD/R-treated PC12 cells, further supporting its role in cellular repair. A Western blot analysis demonstrated the upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H:quinone oxidoreductase 1 (NQO1) and the downregulation of Kelch-like, ECH-associated protein 1 (Keap1) in the cerebral ischemia-reperfusion model. Conclusions: These findings indicate that soy isoflavone confers significant neuroprotective effects against cerebral ischemia-reperfusion injury by enhancing endogenous antioxidant defense mechanisms, reducing oxidative stress, inhibiting apoptosis, and promoting cell migration. The protective effects are likely mediated through the activation of the Nrf2/Keap1 signaling pathway, supporting the therapeutic potential of SI in ischemic stroke treatment.

Mg2+‐Loaded Black Phosphorus Nanosheet Protects against Cerebral Ischemic Injury through Anti‐Oxidative and Anti‐Inflammatory Effects

AbstractIschemic stroke is a severe neurological disease, with high morbidity and mortality worldwide. To date, the treatment of ischemic stroke is limited, and its consequent ischemia‐reperfusion injury is an important reason for this result. Excessive reactive oxygen species (ROS) and inflammatory storm followed by ischemia‐reperfusion alter the microenvironment of cerebral ischemic penumbra, leading to the devastating damage to the brain. Herein, we design a black phosphorus nanosheets (BPNSs) loaded with magnesium ions (Mg2+) and polydopamine (PBP@Mg) to tackle the above problems. BPNSs of PBP@Mg effectively scavenge excessive ROS in neurocytes. Mg2+ plays an anti‐inflammatory role in ischemic penumbra. Furthermore, polydopamine improves the stability of BPNSs. PBP@Mg is subsequently injected into the lateral ventricle of a rat model of ischemic stroke, resulting in an improvement of the ischemic microenvironment and a reduction in ischemic volume. BPNSs of PBP@Mg counteract against the excessive generation of ROS and the neuronal apoptosis in ischemic penumbra. Meanwhile, PBP@Mg dramatically suppresses inflammation by promoting the transformation of microglia from M1 to M2 in ischemic penumbra. PBP@Mg group exhibit a significantly better performance in neurofunctional behavior compared to ischemic group. Taken together, this study provides a novel therapeutic approach for cerebral ischemia‐reperfusion injury via anti‐oxidative and anti‐inflammatory effects.

Implementing psychosocial guidelines into specialized spinal cord injury rehabilitation services to strengthen person-centred health care: protocol for a mixed methods study.

Spinal cord injury (SCI) is a severe neurological disorder resulting in loss of movement and altered sensation with lifelong impacts on health, function, and social integration. Multidisciplinary SCI rehabilitation primarily focuses on enhancing function and independence while simultaneously managing secondary health conditions and providing psychosocial support. Therefore, a major goal in SCI rehabilitation should be strengthening patients' capacity to cope with and adjust to challenges they encounter. Using a mixed methods design, the primary aim of this study is to integrate psychosocial guidelines that promote psychological adjustment into SCI rehabilitation, and second, to evaluate facilitators and barriers to their successful implementation. To determine perceived depth of knowledge, beliefs, and attitudes about psychosocial care, and usage of psychosocial guidelines, healthcare professionals in the three specialist SCI services in New South Wales, Australia will be invited to complete a baseline survey. Following the survey, semi-structured one-to-one interviews and focus groups will be conducted with healthcare professionals representing different health disciplines to understand the context and generate ideas about how best to integrate these guidelines into clinical practice. Based on the surveys, interviews, and focus groups, an implementation intervention employing educational strategies, structural, and nudge (behavioural change) approaches will be designed and implemented over a period of 18-months to facilitate integration of the guidelines into the SCI services. A post-intervention survey with healthcare workers will then be conducted. Focus groups from each SCI service, with representation across the different healthcare professions, will also be conducted to identify facilitators and barriers to implementing the guidelines. Success of implementation will be determined by analyzing any shifts in perceived knowledge, attitudes, and behaviour of staff and cultural/structural processes observed through comparing baseline and post-intervention qualitative and quantitative data. To capture lived experience insight, 10 patients with SCI currently undergoing rehabilitation will be interviewed. This study will establish the success of implementing psychosocial guidelines into three specialist SCI services. It is hypothesized that constructive changes will occur in the knowledge, attitudes, and behaviour of the SCI Unit healthcare professionals, leading to improved psychosocial practices and patient outcomes that will strengthen person-centred healthcare in SCI rehabilitation. This study has been retrospectively registered with the Australian New Zealand Clinical Trials Registry on the 7th of May 2024. The registration number is: ACTRN12624000581561.

Preconditioning and Posttreatment Strategies in Neonatal Hypoxic-Ischemic Encephalopathy: Recent Advances and Clinical Challenges.

Neonatal hypoxic-ischemic encephalopathy (HIE) is a severe neurological disorder caused by impaired cerebral blood flow and brain hypoxia, resulting in high morbidity and mortality rates. While therapeutic hypothermia remains the standard treatment and has been shown to reduce mortality to some extent, its therapeutic efficacy is limited, and it applies only to a select group of neonates who meet stringent inclusion criteria. Advances in our understanding of the pathophysiology of HIE have led to the identification of several promising neuroprotective strategies designed to mitigate or prevent the neurological damage induced by hypoxia-ischemia. Among these, preconditioning has emerged as a potent neuroprotective approach, enhancing cellular resilience to subsequent injury and potentially reducing treatment complexity and healthcare costs. Preconditioning/pretreatment and posttreatment offer significant promise in attenuating the neurological damage associated with HIE. Thus, exploring early intervention strategies for neonatal HIE, focusing on the comparative mechanisms and therapeutic targets of preconditioning and postconditioning, is critical to developing more effective treatment modalities. This review summarizes the current understanding of the pathophysiological mechanisms underlying neonatal HIE and its prevention and treatment strategies, providing new perspectives and a theoretical foundation for future neuroprotective interventions.