NeuroSci最新文献

Lumbar intervertebral disc herniation is a common cause of low back and radicular leg pain, traditionally managed with a combination of conservative therapies and, when indicated, surgical discectomy. An intriguing phenomenon observed in many patients is the spontaneous resorption of herniated disc material over time, often correlating with significant symptom improvement. This article is presented as a narrative review synthesizing experimental, imaging, and clinical literature relevant to spontaneous disc resorption and its implications for clinical decision-making. This paper provides a comprehensive overview of spontaneous disc herniation resorption, exploring the underlying pathophysiological mechanisms and the factors that predict which herniations are likely to regress without surgery. Key mechanisms include inflammatory-mediated degradation of disc fragments, neovascularization with macrophage infiltration and phagocytosis of extruded nucleus pulposus tissue, and biological processes such as enzymatic matrix breakdown and cellular apoptosis that collectively lead to shrinkage of the herniated mass. Patient and disc characteristics that favour spontaneous resorption are identified, such as younger age, extruded or sequestered fragment type, larger initial herniation size, and robust inflammatory response on imaging, whereas certain chronic degenerative changes may reduce this likelihood. We also review current clinical guidelines and expert recommendations on when surgical intervention is warranted versus when conservative management and observation are appropriate. Understanding the probability of natural disc fragment resolution is critical in guiding treatment decisions. In the absence of severe neurological deficits or intractable pain, a period of non-operative management can often be pursued safely, given that the majority of patients experience substantial relief within a few months as discs regress. Conversely, timely surgery is advised for those with neurological compromise or refractory symptoms. By synthesizing the latest evidence on spontaneous disc herniation resorption and its predictors, this review aims to assist neurosurgeons and spine specialists in optimizing patient selection for conservative care and identifying the proper timing for surgical intervention to achieve the best clinical outcomes. Given the narrative design, conclusions are based on synthesis of heterogeneous evidence rather than formal comparative analysis.

Background and aim: Alterations in immune signaling have emerged as a key factor contributing to Parkinson's disease pathophysiology. Increasing evidence also suggests that MASLD and Parkinson's disease may share common immunological mechanisms. Among these, TLR4 has been linked to immune surveillance processes and inflammatory responses in both the central nervous system and the liver. The aim of our study was to delineate TLR4-mediated immune networks underpinning the molecular overlap between MASLD and Parkinson's disease. Methods: Disease-disease and gene-disease associations were systematically retrieved from the DisGeNet database to map TLR4-related molecular networks across both conditions. Functional enrichment analyses were subsequently applied to identify biological pathways significantly associated with TLR4, including potential gene-drug interactions. Guided by these results, a scoping review of the literature was undertaken to summarize existing evidence addressing TLR4-dependent mechanisms in MASLD and Parkinson's disease. Results: DisGeNet analysis indicated 978 shared genes and 39 SNPs shared between both diseases. TLRs, including TLR4-associated coreceptors such as CD14, are among these shared genes. Among these, TLR4 and its missense SNP rs4986791 emerged as key shared immunometabolic nodes linking both diseases. Among the shared SNPs identified in both diseases, we focused on TLR4, where the common variant was rs4986791. Gene set enrichment analysis revealed multiple biological processes associated with cytokine signaling, inflammation, and fibrogenesis. Gene-drug enrichment analysis identified statins and fibrates among the compounds enriched in TLR4-containing networks. Conclusions: These findings support a role for TLR4-associated pathways in linking immunometabolic processes across MASLD and Parkinson's disease. Disruption of these pathways is associated with aberrant inflammatory regulation, with tissue-specific effects further contributing to the distinct molecular pathology observed in each condition. Consequently, modulation of TLR4 signaling represents a plausible strategy for the development or repositioning of disease-modifying interventions applicable to both conditions.

Purpose: The aim of this narrative review is to update current knowledge on Moyamoya vasculopathy (MMV) by addressing key diagnostic debates-including laterality; genetic subtypes; regional epidemiology; and features distinguishing Moyamoya Disease (MMD), Moyamoya Syndrome (MMS) and their mimics.

Methods: Key and representative studies were identified through PubMed/MEDLINE and Scopus, focusing on publications from 2014-2025 while also considering earlier seminal works.

Results: MMD typically presents with bilateral steno-occlusion of the terminal internal carotid arteries (ICAs) and proximal middle and anterior cerebral arteries (MCAs/ACAs) due to concentric vascular thickening, accompanied by characteristic 'puff-of-smoke' collaterals, whereas MMS shows a similar but more often unilateral pattern with fewer collaterals, influenced by the underlying condition. However, this distinction often fails to reflect the full clinical and radiological variability of the Moyamoya spectrum. Atypical moyamoya-like patterns, often confined to M1 or A1 segments, further complicate diagnosis. Clinical manifestations ranged from asymptomatic cases to ischemic or hemorrhagic strokes, and occasionally seizures. Diagnosis relied on multimodal imaging (DSA, MRA, CTA), but genetic mutations, contributing to radiological variability, often complicate differentiation between MMD, MMS, and mimics. Management is pattern-specific: MMS and atypical forms are generally managed conservatively, whereas MMD frequently requires surgical revascularization, particularly in children and symptomatic adults. Nevertheless, variability within diagnostic categories limits the applicability of rigid treatment protocols.

Conclusions: Current diagnostic algorithms remain limited. Integrating advanced imaging findings with clinical, genetic, and epidemiological data is essential to define the full disease spectrum, improve diagnostic accuracy, and inform patient management and outcome assessment.

Multiple sclerosis (MS) pathogenesis involves not only immune-mediated myelin injury but also glial responses. We examined how three charge isomers of myelin basic protein (MBP)-native (C1), phosphorylated (C4), and citrullinated (C8)-modulate rat astrocytes. Cytokines were quantified and grouped (pro/anti-inflammatory, chemotactic, neurotrophic, angiogenic, tissue remodeling), and regulatory markers assessed. C1 strongly upregulated the lipid-sensing receptor LXR, and reduced global DNA methylation; C4 moderately enhanced LXR; C8 failed to activate LXR or alter methylation. Functionally, C1 attenuated IL-1β, IL-6 and GM-CSF while increasing IL-10 and certain chemokines. C4 elicited an intermediate pattern, inducing CX3CL1 (fractalkine), CCL20, VEGF-A and TIMP-1 with minor effects on classical cytokines. In contrast, C8 triggered a robust pro-inflammatory phenotype, increasing IL-1α/β, TNF-α and GM-CSF, with higher IL-10, fractalkine, CCL20, VEGF-A and TIMP-1. All isomers suppressed IFN-γ, IL-4 and CNTF. These data indicate that MBP post-translational modifications drive distinct astrocyte phenotypes through integrated cytokine, metabolic and epigenetic pathways: C1 favors immune regulation and repair, C4 blends inflammatory and reparative cues, and C8 amplifies neuroinflammation. Understanding how modified MBP shapes astrocyte behavior provides mechanistic insight into lesion evolution in MS and suggests astrocyte-directed strategies to modulate neuroinflammation and promote remyelination.

Traditional interoception research investigates cardioception, respiroception, or gastroception as a proxy for the sense of the body as a whole. These single-organ tasks sacrifice construct and ecological validity for a content validity that has been elusive. We propose that interoception is better captured by one's sense of their own autonomic nervous system, or ANSception. The ANS integrates multimodal signals via lesser-myelinated neurons, making it an integral part of the interoceptive nervous system. Thirty-four participants moved a slider to reflect their perceived sympathetic activation (ANSception) while their physiology was monitored. Most participants reported integrating information from two or more organ systems during ANSception. The relationship between ANSception and physiology showed unique but often robust responses by condition and physiological measure. For example, one participant had a negative-to-positive-to-negative pattern for ANSception-EDA correlations from baseline to stimulus to recovery (r = -0.677; 0.657; -0.507, p < 0.001). Another participant had a strong positive correlation between their ANSception and blood pressure (r = 0.601, p < 0.001) during a five-minute reportedly meditative state. We propose that the role of interoception is to scan, integrate and manage information across organ systems, and we conclude that ANSception better captures this role than traditional single-organ tasks.

Background: Intravenous thrombolysis (IVT) is relatively contraindicated in acute ischemic stroke (AIS) patients with intracranial vascular malformations per current guidelines. Thus, the presence of cerebral cavernous malformations (CCMs) may complicate treatment decision-making.

Methods: We performed a literature review of the PubMed, Embase, Scopus, and Web of Science databases through July 2025, identifying reported cases of IVT administration in AIS patients with CCMs. Additionally, we conducted a retrospective cohort study using the Nationwide Readmissions Database (2016-2022) of AIS patients with CCM, and assessed outcomes with IVT versus no IVT treatment. The primary outcome was functional independence at discharge; secondary outcomes included mortality and intracranial hemorrhage (ICH).

Results: Only 34 CCM patients across 7 studies were identified in the literature, with symptomatic ICH occurring in 2 cases (5.9%). In the nationwide cohort, 846 AIS patients with CCMs were included, of whom 240 (28.4%) received IVT. Compared to no IVT treatment, IVT was associated with significantly higher rates of functional independence (46.4% vs. 24.6%, adjusted OR [aOR] 3.04 [95% CI 1.98-4.68], p < 0.001), without significant differences in mortality (8.5% vs. 8.3%, aOR 1.40 [95% CI 0.52-3.76], p = 0.50) or ICH (20.3% vs. 16.1%, adjusted OR 1.01 [95% CI 0.53-1.93], p = 0.97).

Conclusions: The current literature on the safety and efficacy of IVT in AIS patients with CCMs is limited. Our nationwide study suggests that IVT was associated with higher rates of early functional independence without increased risks of hemorrhage or death among patients with CCM.

Alzheimer's disease (AD) is marked by amyloid plaques, hyperphosphorylated TAU proteins, and neuroinflammation. The APP/PS1 mouse model is widely used to study AD pathogenesis. In this study, we investigated the expression of chemokines and their receptors, which may play a role in AD's pathological mechanisms, using brain cortex tissue from female APP/PS1 mice aged 20-21 months. We analyzed several chemokine receptors (CCR1, CCR2, CCR3, CCR4, CCR6, CCR7, CCR9, and CCR10) by Western blot and focused on CCR6, CCR7, and CCR10 using RT-PCR. Additionally, we quantified the levels of chemokines (CCL6, CCL8, CCL19, CCL20, CCL24, and CCL27) by RT-PCR. Our results showed a significant decrease in CCL8 and CCL19, along with their respective receptors, in the APP/PS1 mice compared to controls. On the other hand, we observed a notable increase in CCL6, CCL24, CCL20, CCL27, and their receptors. Chemokines like CCL8 and CCL20, involved in inflammatory responses, may reveal how neuroinflammation contributes to AD. CCL19 and CCL27 are linked to immune cell trafficking, which may help explain immune cell interactions with amyloid plaques and TAU tangles in the CNS. Overall, the altered expression of chemokines such as CCL24 could serve as biomarkers for early AD detection and monitoring disease progression. These findings suggest potential therapeutic targets to modulate immune responses and reduce neuroinflammation in AD.

Background: Prior SMA mortality studies have shown excess mortality in people with SMA, but the literature lacks data on disparities in SMA-related mortality. This study examined disparities in SMA-related mortality in the United States in the post-treatment era (2018-2023).

Methods: This was a population-based study using the CDC Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) database. The International Classification of Disease (ICD), 10th Revision, Clinical Modification codes, G12.0, G12.1, G12.8, and G12.9, were used to identify SMA. The data were stratified by biological sex, race/ethnicity (Non-Hispanic/NH White, NH Black, Hispanic, Asian) and Census regions (West, Northeast, Midwest, South). The analysis was conducted by calculating rate ratios (RR) of age-adjusted mortality rate (AAMR).

Results: There were 821 (45.8% female) SMA-related deaths across the study period. Males were associated with higher AAMR than females (RR = 1.189, 95% CI: 1.035 to 1.366). The SMA-AAMR for NH White individuals was the highest compared to Hispanic individuals (RR = 1.808, 95% CI: 1.420 to 2.300), followed by NH Black and Asian individuals. The West carried the highest AAMR compared to the Northeast (RR = 1.581, 95% CI: 1.263 to 1.978), followed by the Midwest and the South. The age at death distribution showed a bimodal pattern, as follows: 5-14 years and 65-74 years. The infant age group (<1 year) was associated with the highest AAMR compared to all other age groups.

Conclusion: Our findings showed that SMA-related mortality was highest in infants, NH White individuals, the West, and males. These data may assist future efforts to reduce the burden of SMA.

Developmental dyslexia (DD) often involves difficulties in phonological processing of speech.

Objectives: While underlying neural changes have been identified in terms of stimulus- and task-related responses within specific brain regions and their neural connectivity, there is still limited understanding of how these changes affect the overall organization of brain networks.

Methods: This study used EEG and functional network analysis, focusing on small-world propensity across various frequency bands (from δ to γ), to explore the global brain organization during the auditory discrimination of words and pseudowords in children with DD.

Results: The main finding revealed a systemic inefficiency in the functional network of individuals with DD, which did not achieve the optimal small-world propensity. This inefficiency arises from a fundamental trade-off between localized specialization and global communication. During word listening, the δ-/γ1-networks (related to impaired syllabic and phonemic processing of words) and the θ-/β-networks (related to pseudoword listening) in the DD group showed lower local clustering and connectivity compared to the control group, resulting in reduced functional segregation. In particular, the θ-/β-networks for words in the DD group exhibited a less optimal balance between specialized local processing and effective global communication. Centralized midline hubs, such as the postcentral gyrus (PstCG) and inferior frontal gyrus (IFG), which are crucial for global coordination, attention, and executive control, were either absent or inconsistent in individuals with DD. Consequently, the DD network adopted a constrained, motor-compensatory, and left-lateralized strategy. This led to the redirection of information flow and processing effort toward the left PstCG/IFG loop, interpreted as a compensatory effort to counteract automatic processing failures. Additionally, the γ1-network, which is involved in phonetic feature binding, lacked engagement from posterior sensory hubs, forcing this critical process into a slow and effortful motor loop. The γ2-network exhibited unusual activation of right-hemisphere posterior areas during word processing, while it employed a simpler, less mature routing strategy for pseudoword listening, which further diminished global communication.

Conclusions: This functionality highlights the core phonological and temporal processing deficits characteristic of dyslexia.

5a-reductase (5a-R) isozymes are essential for androgen metabolism and neurosteroid biosynthesis, linking endocrinology and neuropsychiatry. This systematic review, conducted in accordance with PRISMA 2020 guidelines, aimed to synthesize current evidence on the tissue distribution of SRD5A1, SRD5A2, and SRD5A3 and their implications in mental health. A systematic search of the PubMed, Scopus, and Web of Science databases up to February 2025 identified 257 articles, of which 83 met the inclusion criteria. SRD5A1 is broadly expressed in the liver, skin, and central nervous system, contributing to allopregnanolone synthesis; SRD5A2 is mainly restricted to androgen-dependent tissues, playing a key role in prostate development and alopecia; and SRD5A3 is associated with glycosylation processes and oncogenesis. Converging evidence suggests that impaired neurosteroidogenesis due to 5α-R inhibition may underlie vulnerability to anxiety, depression, and suicidality. While earlier epidemiological findings were heterogeneous, recent pharmacovigilance data have strengthened the evidence supporting this association. Pharmacovigilance and clinical reports show that a subset of patients treated with finasteride or dutasteride may experience persistent psychiatric and sexual adverse effects, known as post-finasteride syndrome. The current findings underscore the need for careful patient counseling, systematic monitoring, and further translational studies integrating genetics, neuroendocrine markers, and standardized psychiatric outcomes to identify individuals at risk and advance personalized medicine in this field.