Synaptic adhesion molecules (SAMs) are glycoproteins localized on neuronal surfaces, primarily expressed at synaptic plasma membranes. SAMs play a role in inducing formation, maturation, plasticity, and assembly of synaptic connections, which are vital for normal neurodevelopment. SAMs link the pre- and post-synaptic compartments and assist in inter-synaptic signaling and recognition. An increasing variety of SAMs, including neurexins and neuroligins, immunoglobulin (Ig) domain proteins-like synaptic cell adhesion molecule (SynCAM) and neural cell adhesion molecule, receptor phosphotyrosine kinases and phosphatases, as well as various leucine-rich repeat proteins, have been identified. Neurodevelopmental disorders (NDDs), like autism, attention deficit hyperactivity disorder, intellectual disabilities, and cerebral palsy, have been associated with altered SAMs. NDDs are characterized by a spectrum of challenges stemming from abnormal brain development. The etiology of these disorders involves the interaction between genes and environmental factors, such as metals. This review aims to provide a comprehensive overview of the literature, highlighting the role of SAMs in NDDs and potential mechanisms via which neurotoxic metals may contribute to the pathogenesis of NDDs that could involve perturbations in SAMs. Understanding these interconnections will assist in identifying therapeutic targets for these disorders.

Parkinson's disease (PD) is a common degenerative disease of the central nervous system that is characterized by movement disorders and non-motor symptoms (NMSs). The associated NMSs primarily include neuropsychiatric symptoms, autonomic dysfunction, sleep-wake disorders, pain, fatigue, and hyposmia. These NMSs can occur at any stage of PD, especially before the onset of motor symptoms, and may affect a patient's quality of life more than motor symptoms. Although PD is most commonly diagnosed in people over 65 years, some patients exhibit symptom onset before the age of 50, which is clinically known as early-onset Parkinson's disease (EOPD). The high heterogeneity and incidence of EOPD-associated NMSs can lead to the misdiagnosis of EOPD as other neurodegenerative diseases. In this review, we discuss the research progress related to NMSs in patients with EOPD, focusing on neuropsychiatric disorders, autonomic dysfunction, sleep disorders, and sensory impairment, and outline the association of NMSs with different genotypic alterations, with the aim of providing assistance in the clinical management of patients.

The use of iron oxide nanoparticles (IONPs) in magnetic resonance imaging (MRI) and the study of brain functions using MRI have been continuously evolving for more than 30 years. This contribution aims to explore the recent applications of magnetic IONPs in the study of the brain through functional MRI (fMRI), particularly focusing on their use in a specific parameter, that is, the cerebral blood volume (CBV), whose measurements are valued for their higher sensitivity and spatial specificity with respect to blood oxygen level-dependent (BOLD) fMRI analyses. This study will summarize the basis of the fMRI technique, explaining the types of experiments commonly conducted, the parameters involved, and discussing the main techniques that exploit magnetic nanoparticles and other materials as contrast agents, along with their potential applications in the imaging field. CBV measurements will be explained in general theoretical terms and compared with other methods. The key elements of magnetic nanoparticle production, including the most commonly used synthesis procedures and coating options, will be reported. Finally, the discussion will focus on how CBV-weighted (CBVw) images acquired using IONPs are currently being utilized in research.

With the intensification of the aging society, the incidence of various neurodegenerative diseases is on the rise. The hippocampus is susceptible to age-related neuronal decline and is the earliest and crucial region affected in the transition from healthy aging to neurodegenerative diseases. Before the diagnosis of neurodegenerative diseases, there is already a decline in brain energy metabolism, with the disruption of energy metabolism serving as the primary mechanism leading to neuronal damage. This triggers complex signaling mechanisms both inside and outside the brain during the aging process. Glucose serves as the primary energy source for brain tissues, and a decrease in glucose metabolism is an early indicator of age-related functional changes in the brain. Therefore, understanding the pathophysiological basis of glucose metabolism in the aging hippocampus, as well as the underlying mechanisms, is crucial in comprehending cognitive aging. Such understanding is integral for early intervention and the mitigation of memory and learning impairments caused by energy metabolism. In this review, we have delved into the characteristics of energy metabolism, focusing specifically on glucose metabolism, as well as exploring the molecular foundations and associated mechanisms present within hippocampal neuronal cells under both normal and aging conditions. Notably, our investigation has highlighted the vital roles played by ALG5 and STT3A, key molecules involved in N-glycosylation, in influencing GLUT expression and the rate of membrane transport, regulating glucose metabolism, and thereby influencing cellular glucose uptake. The exploration of this study direction holds considerable promise for future endeavors.

The evolving research on the interactions between pain and mental disorders underscores the critical role of neuroimmune interplay in shaping pain perception and mental illness progression. This study employs bibliometric analysis to scrutinize the research landscape, identify emerging hotspots, and forecast future directions. A systematic review of literature from 2014 to 2023 was conducted using CiteSpace software for co-citation analysis, keyword co-occurrence, and burst detection to identify research hotspots and trends. The study examined developmental trends in pain and psychiatric disorder research, highlighting major research institutions and key themes. It unveils pivotal contributors and collaborative networks, showing significant growth in recent years. Emphasis is placed on neuroinflammation and neuroimmunomodulation interactions with mental illnesses. Keyword and thematic clustering analyses highlight the roles of microglial activation, inflammatory mediators, neurotransmitters, and emotional regulation processes. This study paves the way for future inquiries into neuroimmune mechanisms, the development of personalized treatment strategies, and an interdisciplinary approach to enrich our understanding of the biopsychosocial model in these conditions. Future studies should delve deeper into the molecular intricacies of these interactions to develop more effective therapeutic strategies, aiming to enhance patients' quality of life.

Ischemic stroke is the most prevalent cerebrovascular disorder in the clinical setting. It results in associated neurological abnormalities due to a variety of factors, including disruption of cerebral arterial blood flow, hypoxia, and ischemic necrosis of local brain tissues. The neurovascular unit (NVU) is a dynamic structural complex that consists of neurons, glial cells, pericytes, vascular endothelial cells, and the extracellular matrix. Many cells work together to preserve the integrity of the central nervous system (CNS) under physiological conditions. However, following ischemic stroke, NVU homeostasis is disrupted along with the development of tissue ischemia and hypoxia, as well as impaired interactions between various components of the NVU. Collectively, the changes result in increased blood–brain barrier permeability, neuronal dysfunction, and functional destruction of nerve conduction bundles, ultimately leading to the clinical manifestation of neurological deficits including motor, cognitive, and speech impairments that hinder the rehabilitation process. In recent years, with continuously expanding research on ischemic cerebrovascular disease, the role of interconnections between different cells in the NVU in ischemic stroke has received increasing attention. To describe new concepts for the prevention and treatment of ischemic cerebrovascular illnesses, this article reviews the interplay between NVU in the pathogenesis of ischemic stroke.

The appropriate acute treatment strategy for minor ischemic stroke, defined as National Institutes of Health Stroke Scale scores ≤5, is not as well-defined. Prior studies have demonstrated mixed results regarding the effects of neurovascular interventions on minor stroke patients for optimizing the chances of symptomatic improvement. We performed a retrospective single-center study across 6 years to determine the association between thrombolytics and the likelihood of clinical symptom improvement by 24 h in minor stroke patients across ages. Margin plots were derived from multivariable regression analyses. Of 1172 minor stroke patients, in patients <70 years of age, there was greater than 50% likelihood of improvement with any type of thrombolytic administration. When substratifying by type of thrombolytic, there is greater than 50% odds of improvement in patients <80 years of age treated with alteplase and <70 years of age treated with tenecteplase. Thus, the association between age and likelihood of benefit after thrombolytic treatment in minor stroke patients highlights particular minor stroke subpopulations, particularly younger patients, who may benefit from thrombolytic treatment.

Perioperative neurocognitive disorders (PNDs) are one of the most common complications in perioperative patients, and neuroinflammatory reaction mediated by microglia plays a key role in their formation, but the underlying mechanism remains unknown. Given that the triggering receptor expressed on myeloid cells 1 (TREM1) is a key regulator of inflammation, this study aimed to observe the role of TREM1 on the sevoflurane-induced inflammatory activation in microglia. BV2 microglia were subjected to varying sevoflurane concentrations and durations to assess their viability using CCK8 and the expression of TREM1, iNOS, and ARG using enzyme-linked immunosorbent assays. Additionally, TREM1 knockdown lentivirus was employed to examine its impacts on microglia response to sevoflurane and altered expression of inflammatory markers, IL-1β, TNF-α, TGF-β, IL-10, iNOS, and ARG, as detected using qRT-PCR and immunofluorescence for INOS/Iba-1 and ARG/Iba-1. Our findings underscore the potent inflammatory activation induced by prolonged, high-concentration sevoflurane exposure on microglia. We highlight the potential role of TREM1 as a modulator of microglial polarization and a potential target for the treatment and prevention of sevoflurane-induced PNDs.

Myasthenia gravis (MG) is an autoimmune disorder driven by pathogenic IgG autoantibodies, leading to muscle weakness and impaired quality of life. Conventional immunosuppressant therapies are often limited by side effects and incomplete efficacy. Nipocalimab-aahu (N-a), recently FDA-approved, is a novel neonatal Fc receptor (FcRn) antagonist that reduces circulating IgG levels, targeting the underlying disease mechanism. This review synthesizes evidence on N-a's efficacy, safety, and clinical positioning. Phase 2 and 3 trials (Vivacity-MG/MG3) demonstrated that N-a significantly improves the Myasthenia Gravis Activities of Daily Living (MG-ADL) score compared to placebo, with a favorable safety profile. The most common adverse events were nasopharyngitis and headache, with no increased serious infection risk or clinically significant hypoalbuminemia. Compared to other biologics, N-a offers a distinct mechanism, selective IgG reduction without broad immunosuppression and a convenient bi-weekly dosing regimen. While it shows promise for reduced systemic immunosuppression and potentially greater efficacy in MG-ADL improvement than some alternatives, cross-trial comparisons are limited. Key limitations include the need for long-term safety data and more research in underrepresented populations, including pediatric and seronegative patients. In conclusion, N-a represents a significant advancement in generalized MG (gMG) treatment, providing a targeted, effective, and well-tolerated option that addresses a key unmet need for patients with acetylcholine receptor (AChR) or muscle-specific kinase (MuSK) antibody-positive disease.