Trained immunity is the ability of the innate immune system to mount a heightened response to an environmental stimulus after a previous encounter with a noxious trigger. This effect is mediated by metabolic rewiring and epigenetic reprogramming in innate immune cells. In the context of neuroinflammation, trained immunity may represent a major contributor to the pathogenesis of neurological diseases, exerting both detrimental and potentially beneficial effects. While the general mechanisms and systemic implications of trained immunity are widely discussed, evidence in central nervous system (CNS) diseases remains fragmented and largely confined to individual pathological conditions. As a result, a comprehensive framework integrating these findings and identifying shared mechanisms across neurological disorders is still lacking. In this review, we explore the concept of trained immunity with a focus on neuroinflammatory and neurodegenerative diseases, synthetizing evidence from multiple CNS pathologies, including multiple sclerosis, Alzheimer's disease, Parkinson's disease, and cerebrovascular disorders. We first critically examine preclinical and experimental studies addressing innate immune memory in the CNS and subsequently integrate these findings with emerging clinical evidence, aiming to identify convergent mechanisms and disease-relevant immune memory signatures. Finally, we discuss potential therapeutic targets identified in preclinical settings and outline key unresolved issues, including the nature of triggering stimuli, thresholds, and temporal dynamics shaping innate immune memory in the CNS. By highlighting current limitations and defining critical questions for future research, this review presents a unifying perspective on trained immunity in neurological diseases and underscores the translational potential to modulate neuroinflammation and to influence disease progression.

Voltage-gated sodium channels (Navs) selectively conduct Na+ to generate action potentials. Na+ permeates Navs with significantly higher efficiency than many other cations, but Li+ can also permeate Navs to an extent comparable with Na+. Li+ in the blood is known to enter cells via Navs and to have a beneficial effect on various neuropathies. However, the molecular basis of the high Li+ selectivity of Navs was unclear. In this study, using a prokaryotic Nav, we successfully created the first Nav mutant to be more selective for Li+ than for Na+. Electrophysiological and crystallographic analyses suggested the critical determinants of high Li+ selectivity: the strong electrostatic interaction between the ion pathway and hydrated ions, and the smaller number of hydration water exchanges within the ion pathway. Additionally, the extensive interactions around the ion pathway were shown to support monovalent cation selectivity. New drug directions based on the molecular basis for Li+ permeation may target various neurological disorders and could clarify the broader biological effects of lithium.

Recent advances in traditional Chinese medicine-mediated regulation of microglial metabolic reprogramming in neurological disease therapy.

Introduction: Co-ordinated hip, ankle, and stepping strategies play a crucial role in postural control, which is often impaired in patients with neurological conditions such as stroke, multiple sclerosis, Parkinson’s disease, and Diabetic Peripheral Neuropathy (DPN). Despite their widespread clinical use, the available evidence has not been systematically mapped to determine their effects on balance and gait parameters. Aim: To collate, synthesise, and report existing evidence on the effects of hip, ankle, and stepping strategy training (SST) on balance and gait parameters among individuals with neurological conditions. Materials and Methods: This scoping review followed PRISMA-ScR guidelines. The review protocol was registered on the Open Science Framework (OSF) with the registration DOI: 10.17605/OSF.IO/CAF63. Three electronic databases— PubMed, Scopus, and ScienceDirect—were searched for studies published in the English language. The search strategy included relevant keywords, Boolean operators (AND, OR, NOT), Medical Subject Headings (MeSH) terms, and filters such as publication year range, randomised clinical trials, and language. Results: Fourteen studies were included in this scoping review. Study characteristics were summarised based on the populations investigated, types of postural-strategy training employed (hip, ankle, and stepping strategies), and intervention duration. Ankle Strategy Training (AST) on unstable surfaces demonstrated significant improvements in Centre Of Pressure (COP) sway. When combined with Hip Strategy Training (HST), greater improvements were observed in proximal extremity control and limits of stability. Several studies also reported that perturbation-based training enhanced reactive balance by increasing tolerance to perturbation intensity, improving confidence during community mobility, reducing fall risk behaviours, and enhancing gait parameters. Conclusion: Postural-strategy training improves balance and gait parameters in individuals with neurological conditions. Each strategy offers distinct benefits, while multistrategy training yields greater functional improvements than single-strategy interventions.

Neurological disorders affect both the central and peripheral nervous systems, exhibiting broad genetic and clinical variability and posing a significant public health concern. These conditions range from common disorders, such as attention deficit disorder and epilepsy, to rare diseases like intellectual disability (ID) and white matter disorders. Exome sequencing (ES) has emerged as a powerful tool in diagnosing the genetic underpinnings of these disorders. ES demonstrated its feasibility as a cost-effective diagnostic pathway by identifying pertinent diagnostic outcomes in 29.4% of cases and being noticeably more cost-effective than conventional genetic diagnostic techniques. This study investigated the genetic basis of three rare neurological disorders in three unrelated Pakistani families using ES. Each family presents with a distinct syndromic form of ID, associated with bilateral frontoparietal polymicrogyria (BFPP) (Family-1), Li-Ghorbani-Weisz-Hubshman syndrome (LIGOWS) (Family-2), or hypomyelination and congenital cataract (HCC) (Family-3). The functional consequences of the missense variants were investigated using bioinformatic prediction tools to confirm the pathogenicity. In Family-1 with BFPP, ES identified a novel homozygous missense variant ((NM_001145771.3): c.1579C>T; (NP_001139243.1): p.Pro527Ser) in ADGRG1, predicted to impact protein function. In Family-2 with LIGOWS, a novel homozygous missense variant ((NM_182958.4): c.649A>C; (NP_892003.2): p.Met217Leu) was found in KAT8. In Family-3 with HCC, a novel homozygous nonsense variant ((NM_032581.4): c.722T>G; (NP_115970.2): p.Leu241Ter) was identified in FAM126A, likely resulting in a truncated, nonfunctional protein. Families' structures and segregation analysis confirm disease condition segregating with autosomal recessive mode of inheritance. The functional consequences of the ADGRG1 and KAT8 missense variants were revealed as deleterious using bioinformatic prediction tools. We have identified novel pathogenic variants in ADGRG1, KAT8, and FAM126A in individuals with rare neurological disorders, thereby expanding the genetic and clinical spectrum of these conditions. This study reports, for the first time, an autosomal recessive inheritance pattern for a KAT8-related disorder, providing new insights into its genetic architecture.

Primary Total Knee Arthroplasty in Patients Who Have Neuromuscular Disorders and Genu Recurvatum Using a Rotating-Hinge Implant: A Case Series With a Mean 4-Year Follow-Up.

Impact of microplastics on human health: A critical role of gut microbiota.

Senegenin attenuates LPS-induced neuroinflammation and microglial cell death via Akt phosphorylation and suppression of cGAS-STING-NLRP3 signaling: Network pharmacology and experimental validation.

Seroprevalence and risk factors for Neospora caninum infection in goats in the state of Goiás, Brazil.

α-asaronol alleviates seizures, neuroinflammation and cognitive deficits in a mice model of lithium-pilocarpine-induced seizures.

Generalizable prediction of hand motor behaviour from spontaneous brain connectivity.

ObjectiveThis cross-sectional study aimed to identify electrophysiological markers distinguishing stages of development, stability, and early aging in cortical auditory processing to elucidate neurophysiological changes in healthy auditory aging.MethodsWe evaluated 149 healthy participants (both sexes; aged 7-59 years) recruited from the general community via electronic media, posters, radio, and regional television, divided into six age groups (7-11, 12-17, 18-29, 30-39, 40-49, and 50-59 years). Eligibility criteria included normal hearing, no neurological disorders, and normal otoscopy. Cortical auditory evoked potentials (CAEPs) were recorded using the syllable /da/ (binaural stimulation, 70 dB HL) with eye-movement control.ResultsSignificant differences in P1 latency were observed between children (7-11 years) and older participants (12-59 years). N1 latency differed between children and adults (30-59 years), while N1 amplitude varied between adolescents (12-19 years) and adults aged 40-49 years. P1-N1 latency differed between adolescents and adults aged 40-59 years. Age correlated moderately negatively with P1/N1 latencies and weakly positively with N1 amplitude.ConclusionMaturational changes in P1/N1 latencies were evident, but no decline occurred during adulthood or pre-senescence, suggesting stable auditory processing until at least age 59.

Introduction: The Zika virus (ZIKV), transmitted primarily by Aedes mosquitoes, has caused significant public health concern due to its association with congenital abnormalities, including microcephaly, and neurological disorders such as Guillain-Barré syndrome. It was first discovered in Uganda in 1947, with its most significant global outbreak occurring between 2015 and 2016. Methodology: A comprehensive literature review was conducted using PubMed, Scopus, the World Health Organization (WHO), and the Centers for Disease Control and Prevention (CDC) databases, covering the period from 2000 to 2024. The search strategy incorporated relevant keywords such as “Zika virus,” “ZIKV epidemiology,” “ZIKV vaccine,” “Aedes mosquitoes,” and “Zika congenital syndrome.” Results: The Zika virus primarily spreads via Aedes mosquitoes, with sexual and congenital transmission also contributing to its spread. The virus has posed significant public health challenges, particularly among pregnant women, resulting in birth defects. Recent data from India highlights an increase in Zika virus cases, especially in Maharashtra and Karnataka. Current preventive measures include vector control, safe sexual practices, and public health campaigns; however, a vaccine is still under development. Discussion: Despite global efforts, the Zika virus continues to threaten maternal and neonatal health, particularly in endemic regions. Its resurgence in areas like India signals the need for proactive containment and education strategies. Conclusion: The Zika virus remains a serious global health threat. There is an urgent need for continued surveillance, effective prevention strategies, and vaccine development to mitigate its impact. Enhanced public awareness and ongoing research are critical to managing Zika-related health risks.

• In-depth study of the impact of intensity value regularization on 3D MRI segmentation methods: nnU-Net, WNet, and Primus. • A broad range of five intensity regularization approaches used in deep learning literature has been included. • The analysis focuses on the influence of the number of channels in deep learning architectures, specifically structural elements like Convolutional Neural Networks, Transformers, and hybrid models. • Comprehensive dataset compendium: three relevant open-access neurological disorders datasets were considered: glioblastoma, multiple sclerosis, and epilepsy, using T1 and FLAIR MRI sequences. • An exhaustive statistical analysis was conducted to evaluate the reported results and support the findings thoroughly. In this work, a comprehensive analysis of the impact of intensity value regularization methods on 3D MRI segmentation for three neurological disorders: glioblastoma, multiple sclerosis, and epilepsy, is presented. The experiments were conducted through three architectures: nnU-Net (convolutional neural network), WNet (hybrid combining convolutional and transformer elements), and Primus (transformer-based), considering both FLAIR and T1-weighted images, as well as FLAIR-only scenarios. The statistical analysis conducted underscores the crucial role of intensity regularization in the performance. The results indicate that among the intensity regularization methods tested in this study, KDE, White-stripe, and Z-score standardizations proved to be particularly effective. Furthermore, nnU-Net is the most robust architecture against intensity variability, with small improvements of around 3%. Meanwhile, methods incorporating TF elements are more sensitive to these variations. WNet demonstrates slightly greater gains, around 6%. While Primus can be less stable and underperform compared to nnU-Net and WNet in most cases; nonetheless, it remains a promising and competitive option. Additionally, it has been demonstrated that adding an extra channel does not necessarily guarantee improved performance, while also increasing computational cost.

Visual Field Testing: The Key to Localizing Afferent Visual Pathway Lesions.

The heparan sulphate proteoglycan, Glypican-4 (GPC-4), is an integral component of cell surfaces that fulfils key functions as a modulator of cell communication. Over time, human GPC-4 (hGPC4) has gained recognition as a valuable target for enhancing the therapeutic potential of human pluripotent stem cells (hPSCs). hGPC-4 is also a promising diagnostic and therapeutic target for a range of developmental and neurological disorders, as well as cancer. Its involvement in multiple biological processes and its impact on cellular signaling pathways make it a compelling candidate for future research and clinical applications. Here, we report RB1 and RB3 as the first hGPC-4-specific nanobodies. Both RB3 and RB1, bind recombinant hGPC4 with affinities in the tens of nanomolar range, whereas only RB1 recognizes native, cell-expressed hGPC4, highlighting its potential for functional studies. Notably, the bivalent nanobody Fc-fusion form of RB1, termed RB1-Fc, demonstrates a significant ∼14-fold increase in apparent binding affinity on cells when compared to the monovalent RB1. Furthermore, binding of RB1-Fc to hGPC-4 is dependent on the native conformation of hGPC-4, demonstrating that RB1-Fc is a conformational nanobody. Notably, RB1-Fc neutralizes the activity of GPC-4, as shown by our functional studies in hPSCs. These studies demonstrate the potent efficacy of the lead hGPC4 nanobodies, RB1-Fc and RB3. They also provide a solid rationale for using these nanobodies in the detection and characterization of physiologically and clinically relevant hGPC-4. Additionally, their potential as agents for therapeutic targeting of hGPC-4 opens new avenues for treating disorders associated with dysregulated hGPC-4 activity.

Transcription factor EB as a therapeutic target for intracerebral hemorrhage: A review.

The cerebellin (CBLN) family includes CBLN1, CBLN2, CBLN3, and CBLN4, which are important secreted glycoproteins that play roles in synaptogenesis and the maintenance and plasticity of synapses across various regions of the central nervous system (CNS). Generally known for their implications in cerebellar parallel fiber-Purkinje cell synapses, CBLNs also play a comprehensive role in synaptic regulation in the CNS. By forming trans-synaptic complexes with postsynaptic glutamate delta receptors (GluDs) and presynaptic neurexins (NRXNs), CBLNs significantly impact the synaptic specificity and potency. Each CBLN protein has its own expression signature and function. Current research points to a key role for CBLN1 in forming excitatory synapses, especially in the cerebellum, while CBLN2 is reported to regulate inhibitory synaptic transmission and serotonergic circuits. In addition, CBLN3 regulates synaptic stability and is associated with many neurodevelopmental problems. Apart from its role in the regulation of inhibitory synapse formation, CBLN4 is also linked to many neurodegenerative disorders. Dysfunction of pathways associated with CBLN signaling has been linked to several neuropsychiatric and neurological disorders, such as ataxia and schizophrenia. This review article compares existing data on the structure, expression, and functional properties of CBLN proteins, their roles in synapse organization, and their potential as therapeutic targets for neurological disease.

Artificial intelligence and machine learning driven nanorobotics for targeted brain delivery: Redefining blood-brain barrier navigation.

Mechanisms and therapeutic potential of migrasomes in neurological disorders.