Neuroprotection最新文献

Pediatric neurological disorders comprise diverse conditions that impair nervous system function in children and contribute substantially to global disease burden. Stem cell therapy has become a promising treatment in neurology due to the cells' ability to self-renew, ensuring a continuous supply of cells. Cells are harvested from various origins, notably embryonic tissues and adult sources such as bone marrow, adipose tissue, and umbilical cord. Therapeutic effects arise from cell or enzyme replacement, trophic support, immunomodulation, and paracrine actions of the secretome. This review summarizes clinical applications of stem cell therapies across pediatric neurological diseases-including autism spectrum disorder, cerebral palsy, traumatic brain and spinal cord injury, epilepsy, neuromuscular disorders, and lysosomal storage diseases-and appraises evidence from preliminary descriptive studies that update the field and reveal methodological limitations. Reported therapeutic effect differs markedly by cell type, disease biology, timing of intervention, dose, and delivery method, producing inconsistent clinical results. Positive functional or developmental improvements have been documented in selected reports, but safety concerns, heterogeneity in study design, short follow-up, and variable potency assays limit conclusions. Because stem cell populations share phenotypic features but vary in therapeutic capacity, a universal, one-size-fits-all strategy is unlikely to succeed. Critical gaps remain regarding long-term safety, durability, standardized manufacturing, and optimal clinical endpoints. Continued rigorous translational research, standardized clinical trials, and expanded long-term surveillance are essential to optimize these therapies and improve outcomes for affected children and to ensure equitable access for diverse pediatric populations worldwide and sustainable implementation.

Neuroinflammation is increasingly recognized as a critical driver of central nervous system (CNS) disorders, and network pharmacology has emerged as a promising approach to elucidate its complex mechanisms and therapeutic strategies. This study provides a comprehensive bibliometric and scientometric analysis of publications over the past 13 years to characterize research trends, identify key contributors, and uncover core therapeutic targets in this field. Articles published between January 2012 and May 2024 were retrieved from the Web of Science Core Collection. Visualization and quantitative analyses were performed using CiteSpace (version 6.3.R1, Drexel University, PA, United States) and VOSviewer (version 1.6.20, Leiden University - CWTS, Netherlands) followed by network interaction analysis to identify central targets implicated in neuroinflammation. A total of 156 publications were analyzed, with the United States, China, and Germany leading global output. Beijing University of Chinese Medicine, Case Western Reserve University, and University System of Ohio were identified as the most influential institutions. Nucleic Acids Research was the most frequently cited journal, whereas Journal of Ethnopharmacology contributed the largest number of publications. Co-occurrence clustering revealed 13 thematic research areas, highlighting apoptosis, Panax notoginseng, dihydrochalcones, and quercetin as representative hotspots. Target interaction analysis identified signal transducer and activator of transcription 3 (STAT3), jun proto-oncogene (JUN), AKT serine/threonine kinase 1 (AKT1), tumor protein 53 (TP53), and interleukin-6 (IL6) as core molecular targets. The findings delineate a dynamic and evolving research landscape in this domain and clarify its organization around several pivotal molecular targets. The field is shifting away from the conventional "one drug, one target" paradigm toward multi-target therapeutic strategies, reflecting the multifactorial nature of neuroinflammation in CNS disorders. These insights highlight key molecular nodes and research directions, providing a foundation for precision medicine approaches and innovative drug development to improve treatment outcomes in neuroinflammatory CNS diseases.

Compelling evidence indicates a significant connection between dysfunction of the gastrointestinal tract, the gut microbiome, and Parkinson's disease (PD), which aligns with the notion of the "gut-brain axis". While the exact mechanisms involved in gut-brain interactions are still not fully understood, the high incidence of gastrointestinal symptoms during the early stages of PD aids in the development of diagnostic biomarkers and prospective disease-modifying therapies. Importantly, a number of studies have revealed a possible association between gallstone disease (GD) and PD; nevertheless, the exploration of diverse risk factors and the theory suggesting that the onset of PD might be associated with GD requires further investigation. This review aims to explore the evidence that connects alterations in GD with PD, emphasizing mechanisms that promote gut dysbiosis, the gut-brain connection, changes in lipid profiles, genetic and dietary influences, as well as neuroinflammation. Furthermore, we assess the potential implementation of innovative therapeutic strategies, including probiotic treatments and gut microbiota transplantation, in patients with PD. Although the evidence supports an association between PD and GD, causality remains to be established. Prospective cohort studies are needed to determine whether gallstones represent a prodromal marker or a causal risk factor for PD, and to validate these pathways as novel diagnostic and therapeutic targets for PD.

Glial cells, alongside neurons, are the major cells of the central nervous system. More than just supporting neurons, glial cells are vital in central nervous system homeostasis and actively shape neurodegenerative disease mechanisms. They exhibit dual roles in promoting neuroprotection through glutamate clearance, mitochondrial transfer, extracellular vesicle signaling, and remyelination, yet also contributing to excitotoxicity, neuroinflammation, and myelin loss. Recent studies emphasize their therapeutic potential, such as enhancing excitatory amino acid transporters, engineering extracellular vesicles, and boosting oligodendrocyte precursor cell function in combating neurodegeneration. This mini review comments on previous articles published in Neuroprotection alongside others, and discusses how enhancing glial protective roles may serve as novel neuroprotective interventions.

Background: Aging affects almost all aspects of central nervous system (CNS) function, including the blood-brain barrier (BBB). Here, we use cell culture models to ask whether senescence, a cellular feature of aging, alters the BBB by modifying interactions between astrocytes and brain endothelial cells.

Methods: Human astrocyte and Human brain microvascular endothelial cells were subcultured and maintained for cells at low and high passages, then confirmed with senescence-associated β-galactosidase staining and gene expression of cyclin-dependent kinase inhibitor 2A (Cdkn2a). After coculturing with astrocyte, the Alexa Fluor 488-labeled bovine serum albumin (Alexa 488-BSA) was used as a tracer to measure the permeability of brain endothelial cells; the expression of related proteins was measured by quantitative real-time polymerase chain reaction. Reducing the angiotensinogen (AGT) by small interfering RNA (siRNA) in senescent astrocyte to test the effect of angiotensin signals on endothelial permeability.

Results: Young astrocytes (cumulative population doublings [CPD] ≤ 4) modified the expression of barrier genes and decreased brain endothelial permeability in coculture, whereas aged senescent astrocytes (CPD ≥ 9) had no effects (45.5% ± 18.0% vs. 122.8% ± 28.6%, p = 0.0016). Angiotensin is known to alter the BBB. Its precursor, AGT, is highly expressed in astrocytes in the brain. Therefore, we asked whether angiotensin signaling may mediate the loss of endothelial barrier-promoting properties in senescent astrocytes. Both protein and messenger RNA (mRNA) levels of AGT were increased in high-passage senescent astrocytes. Reducing AGT levels through siRNA restored the endothelial barrier-promoting effects of high-passage senescent astrocytes (F _(2,15) = 6.508, p = 0.0092). By contrast, brain endothelial cells at different passages did not change the expression of AGT in astrocytes.

Conclusion: Taken together, these findings suggest that increased angiotensin signaling from astrocytes to brain endothelium may partly mediate the decrease of BBB function in the aging CNS.

Hemichorea-hemiballism is classically associated with the contralateral basal ganglia, particularly involving the putamen and subthalamic nucleus, whereas cortical involvement remains a rare etiology. In this case, we present a patient with acute hemichorea-hemiballism secondary to multiple cortical infarcts demonstrated by neuroimaging. We review the literature to explore further significance of cortical-basal ganglia circuit dysfunction in movement disorders. This case highlights both the necessity of considering atypical infarction patterns in acute dyskinesia presentations and the importance of early imaging evaluation combined with targeted therapeutic interventions.