Search Results (13,967)

Garrya flavescens S. Wats. (GF) has been traditionally used to treat gastrointestinal spasms, yet its bioactivity within the central nervous system remains unexplored. This study aimed to characterize the bioactive constituents of GF and evaluate its anti-inflammatory and metabolic regulatory effects in lipopolysaccharide-activated microglia. Phytochemical profiling using LC-HRMS and HPLC identified rutin as a primary bioactive component, present at an exceptionally high concentration (9309 μg/g). In BV-2 microglial and RAW 264.7 cells, GF treatment significantly suppressed the expression of pro-inflammatory cytokines and mediators in a dose-dependent manner. Mechanistic studies revealed that GF specifically modulated the ERK signaling pathway. Furthermore, Seahorse XF analysis demonstrated that GF restored mitochondrial homeostasis by reducing basal respiration and proton leak while significantly enhancing spare respiratory capacity. Finally, conditioned medium from GF-treated microglia improved the viability of N2A neuronal cells. These findings highlight GF as a potent botanical source with significant neuroprotective potential, offering a promising candidate for functional food or nutraceutical applications targeting neuroinflammatory disorders. Full article

Nanogrooves provide instructive cues to cells in culture. Several nanofabrication techniques have been developed to create biomimetic substrates, advancing our understanding of cell adhesion. Their integration into nervous system models highlights the critical role of the extracellular matrix (ECM) in developing functional tissue constructs for in vitro platforms such as Brain-on-Chip (BoC) and Nervous System-on-Chip (NoC). This study presents a nanofabrication approach that integrates photolithography and microtransfer molding (μTM) to pattern nanogrooves using photocurable polymer NOA81 onto microelectrode array (MEA) plates. The resulting nanogrooves exhibited a pattern periodicity of 976 nm and a ridge width of 232 nm, as confirmed by scanning electron microscopy and atomic force microscopy. We assessed the biocompatibility and functional impact of these modified substrates using human induced pluripotent stem cell (hiPSC)-derived neuronal cultures. Neurons cultured on nanogroove-modified MEAs exhibited aligned neural processes due to the anisotropic surface features and expressed vivid spiking behavior and higher burst frequency compared to randomly cultured neuronal networks. In conclusion, the proposed fabrication technique integrates nanogrooves with commercial MEAs using a combination of microtransfer molding and photolithography, resulting in modified culture substrates that enhance spike activity and network organization, aiding in the development of more in vivo-like neural models. Full article

Chronic pain, a complex multidimensional disorder, remains a major healthcare issue and a therapeutic challenge. Neuropathic pain is a chronic pain condition that results from damage or dysfunction in the nervous system. While mechanisms of neuropathic pain at the peripheral and spinal cord level have been extensively studied, pain mechanisms in the brain remain underexplored. The amygdala, a limbic brain region, has emerged as a critical brain area for the emotional–affective dimension of pain and pain modulation. Amygdala neuroplasticity has been associated with pain states, but the exact molecular and cellular mechanisms underlying these states and the transition from acute to chronic pain are not well understood. Here, we used the spinal nerve ligation (SNL) model of neuropathic pain in male rats to investigate changes in gene expression in the amygdala at the chronic pain stage using RNA sequencing (RNA-Seq). Two amygdala nuclei, the basolateral (BLA) and central (CeA), were investigated in a hemisphere-dependent manner. We used an integrative approach that focuses on functional significance and cell-type specificity of differentially expressed genes (DEGs) to nominate mechanistic targets for central regulation of chronic pain. Our integrative transcriptomic and bioinformatic analyses identified individual genes (e.g., Cxcl10, Cxcl12, Mbp, Plp1, Mag, Mog, Slc17a6, Gad1, and Sst), molecular pathways (e.g., cytokine-mediated signaling pathway), biological processes (e.g., myelination, synaptic transmission), and specific cell types (e.g., oligodendrocytes, glutamatergic, and GABAergic neurons) affected by chronic pain. Our results also provide some evidence for the emerging concept of hemispheric lateralization of pain processing in the amygdala. Overall, our study proposes oligodendrocyte dysfunction in the amygdala, neuroimmune signaling in the CeA, and glutamatergic neurotransmission in the BLA as key processes and potential therapeutic targets for the management of chronic neuropathic pain. Full article

Background and Objectives: Functional neurosurgery encompasses surgical interventions aimed at modulating the function of the central and peripheral nervous systems. Spinal cord stimulation (SCS), as a form of neuromodulation, is an established treatment for chronic pain and is increasingly utilized by both anesthesiologists and neurosurgeons. The aim of this study was to evaluate the effectiveness of SCS in patients with chronic neuropathic spinal pain. Materials and Methods: This prospective study included 42 patients who demonstrated a positive response to trial stimulation. Only patients achieving a clinically meaningful response (≥50% pain reduction) during the trial phase were included in the final analysis. Pain intensity and functional disability were assessed using the Visual Analog Scale (VAS) and the Oswestry Disability Index (ODI). All patients underwent a two-stage percutaneous implantation procedure using burst stimulation. A follow-up assessment was performed 3–6 months after implantation. Results: A statistically significant reduction in pain intensity was observed (p < 0.0001), with median VAS scores decreasing from 8 to 3, corresponding to a 62.5% reduction in pain intensity and exceeding the minimal clinically important difference (MCID) for VAS. Functional status improved significantly, with ODI scores decreasing from 74% to 38%, markedly surpassing the established MCID threshold. A clinically meaningful reduction in pain (≥50%) was achieved in the majority of patients. All patients requiring opioid analgesics at baseline discontinued their use following SCS implantation, and a reduction in overall analgesic consumption was observed across the cohort. Conclusions: These findings suggest that burst SCS may be an effective treatment option for carefully selected patients with chronic neuropathic spinal pain who are not candidates for conventional spine surgery. However, the results should be interpreted with caution due to the enriched study design and limited follow-up period. Full article

Delayed cerebral ischemia (DCI) is a major complication of aneurysmal subarachnoid hemorrhage (aSAH), strongly associated with neurological deterioration and poor outcomes. Its pathophysiology remains incompletely understood and involves multiple interacting processes. Increasing evidence highlights the role of redox imbalance triggered by hemoglobin breakdown and the subsequent generation of reactive species, leading to vascular dysfunction, impaired nitric oxide signaling, and inflammatory activation This review aims to summarize current knowledge on redox-related mechanisms involved in DCI and to explore the potential role of the peroxiredoxin (PRDX) family in this setting. A narrative review of experimental and preclinical studies was performed, focusing on molecular pathways associated with vascular regulation, cellular injury, and antioxidant defense. Particular attention was given to the distribution and biological functions of PRDX isoforms within the central nervous system. This work addresses a topic not previously systematically discussed, the potential involvement of PRDX proteins in aSAH-related complications. By integrating available data, it provides a conceptual framework linking PRDX to mechanisms relevant for DCI. The manuscript serves as a starting point for future research, particularly translational and clinical studies in humans, which are necessary to verify the relevance of these findings and to better understand their potential clinical implications. Full article

Mast cells are heterogeneous, tissue-resident immune sentinels best known for their roles in allergy and peripheral inflammation. The discovery of mast cells within the meninges and brain parenchyma over a century ago raised enduring questions regarding their function in the central nervous system (CNS), their ontogeny, and distinction from peripheral counterparts. Brain mast cells are sparse and predominantly located in perivascular niches rather than forming dense aggregates, a feature that has made them difficult to study. Nevertheless, accumulating evidence implicates mast cells in diverse aspects of CNS physiology and pathology, including regulation of blood–brain barrier permeability and neurovascular function, as well as immune surveillance in contexts of infection and injury. The ability of mast cells to communicate with neighboring glial and neuronal networks suggests potential roles in modulating neural activity, development, and behavior, although this dimension remains incompletely understood. Much of the foundational literature predates advanced immunological tools, contributing to persistent misconceptions regarding the identity and significance of brain mast cells. In this review, we outline the history of research investigating this enigmatic aspect of mast cell biology, clarifying what is known, what remains speculative, and how emerging insights may help redefine the boundaries between classical immunology and neuroscience. Full article

Background: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system and is the leading cause of neurological disability. Currently, the main strategy for MS therapy is the use of disease-modifying therapies (DMTs). If low-efficacy DMTs are ineffective, patients are transferred to high-efficacy DMTs, which possess more severe side effects associated with immunosuppression. Therefore, the search for new add-on therapies for MS that can enhance the effect of low-efficacy DMTs is relevant. Curcumin, being a natural polyphenol, has immunoregulatory properties and a favorable safety profile. In addition, micellar forms of curcumin can increase its bioavailability. We studied the effect of micellar curcumin on clinical and laboratory parameters in patients with MS receiving low-efficacy DMTs (IFN-β). Methods: Sixty patients with MS and a suboptimal response to IFN-β were randomized (1:1) into two groups: the IFN-CUR group, which received add-on therapy with micellar curcumin (containing curcumin and Tween 80 as a solubilizer) for 6 months, and a control group (IFN group), which received IFN-β alone. The 6-month treatment period was followed by a subsequent 6-month follow-up off curcumin treatment (DMTs only). Results: The proportion of patients without relapses in the curcumin add-on group increased significantly after 6 months (from 57% to 90%, p = 0.007), and the risk of exacerbation was significantly lower compared to the control group (HR = 0.2; p = 0.03). The treatment was associated with EDSS score stabilization, a positive effect on depression (p = 0.05), and a reduction in plasma IFN-γ levels (p = 0.02). A decreasing trend in MRI lesion activity and reductions in specific microbiota-related markers, including the Eggerthella lenta-associated marker (i16a), were also observed. In ex vivo cultures, curcumin significantly inhibited IL-6 production in macrophages derived from patients with multiple sclerosis (MS) and healthy donors. Conclusions: Add-on therapy with micellar curcumin may enhance the efficacy of IFN-β, improving clinical outcomes and modulating inflammatory and microbial parameters in MS patients with a suboptimal response to IFN-β treatment. Full article

Background: Intraventricular central nervous system (CNS) lymphoma is an atypical presentation of extranodal lymphoma, whether primary or secondary. The most commonly diagnosed subtype of lymphoma is diffuse large B-cell lymphoma (DLBCL). There is a documented relation of HIV, EBV and KSHV infections with lymphomagenesis. AIDS-related lymphomas (ARLs) are described as a defining illness of the acquired immunodeficiency syndrome (AIDS). This study presents a novel case and systematic review of clinical, radiographic and histopathological features of intraventricular lymphomas. Methods: We report on a 27-year-old woman with a left lateral ventricle DLBCL with surrounding edema treated with steroids. A systematic review of 147 additional cases (1977–2025) was conducted, analyzing patient demographics, tumor characteristics, clinical features, imaging, treatment, and outcomes. The tumor locations were divided into three groups depending on the extent of ventricular involvement. Descriptive statistics summarized findings. Findings: 147 cases (mean age, 54.2 years; range, 3–87; 63.3% male) were analyzed. Immunodeficiency in patients was unusual (6.1%). Fully intraventricular lesions were the most common presentation (52.4%), with systemic involvement solely in 10 cases (6.8%). The lesions were predominantly located in the lateral ventricles or fourth ventricles (46 times each), and bilateral involvement was noted 37 additional times. DLBCL was diagnosed in 101 cases (78.9%). Interpretation: Intraventricular involvement in central nervous system lymphoma poses a diagnostic and therapeutic challenge due to non-specific symptoms and atypical locations. Adding to the diagnostic difficulty of intraventricular masses in young patients, we wish to highlight that immunocompromised patients are a notably insignificant subgroup of patients in our study. Full article

The skin–brain axis constitutes a complex, bidirectional network integrating cutaneous sensory, immune, and neuroendocrine systems with central neural circuits involved in emotion regulation, stress responsivity, and social cognition. Advances in psychodermatology and cosmetic science have progressively extended this framework to the emerging field of neurocosmetics, which explores how topical formulations, sensorial properties, and cutaneous neuromodulators may influence psychological well-being, affective states, and perceived stress. The aim of this narrative review is to synthesize current evidence on the biological foundations of the skin–brain axis and to critically examine the implications of these mechanisms for neurocosmetic interventions from a psychological and psychiatric perspective. It describes the biological substrates underlying skin–brain communication, including the cutaneous hypothalamic–pituitary–adrenal axis, neuropeptides, neurotrophins, transient receptor potential channels, and endocannabinoid signaling, and examines how these pathways are targeted by neurocosmetic interventions. Particular attention is devoted to neuroactive compounds, such as peptides, cannabinoids, botanicals, and aromatherapeutic molecules, as well as to sensorial strategies involving texture, temperature, and olfactory cues, which may modulate mood, anxiety, and self-perception through peripheral mechanisms. From a psychological and psychiatric perspective, the review discusses the intersection between stress-related skin conditions, body image disturbances, and emotional dysregulation, highlighting how cosmetic practices may influence subjective well-being beyond purely aesthetic outcomes. Methodological limitations of the existing literature, including the heterogeneity of study designs and outcome measures, as well as ethical considerations related to mood- and stress-related claims in cosmetic products, are critically examined. Finally, future research directions are outlined, and a translational framework is proposed to integrate dermatology, neuroscience, and mental health within next-generation cosmetic science. Full article

Peripheral nerves provide a direct connection between the brain and the tumor microenvironment. This connection allows the nervous system to influence processes associated with the development, progression, and metastasis of different tumor types. Therefore, tumor innervation by peripheral nerve fibers is currently emerging as a characteristic that contributes to multiple hallmarks of cancer. Several experimental studies have shown that cancer progression involves actively inducing the ingrowth of autonomic and sensory nerve fibers into tumor tissue. In this process, known as neoaxonogenesis, cancer and other cells in the tumor microenvironment play an important role by synthesizing and releasing neurotrophic factors (e.g., nerve growth factor, brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor), axonal guidance molecules (netrins, semaphorins, ephrins, slits), exosomes (containing microRNA and axonal guidance molecules), and other molecules present in the tumor microenvironment (e.g., granulocyte colony-stimulating factor, leukemia inhibitory factor), which modulate the ingrowth of nerve fibers into the tumor. This results in an increased nerve supply to tumor tissue, which is primarily linked to its growth. However, there are also studies demonstrating the protective effects of increased nerve fiber density against processes associated with cancer progression in certain types of cancer. The findings from these studies contribute to the complexity of neuro-cancer interactions, which is probably based on the type of cancer and the physiological specializations of the nerve fibers in a given organ. Despite contrasting findings, the stimulatory effects of nerve fibers on cancer growth are supported by several studies that described reducing the negative impact of nerve fibers on tumors and thus inhibiting cancer progression. The most significant approaches to reducing neural effects appear to be denervation, the administration of neurotransmitter receptor antagonists, the administration of local anesthetics, and the administration of antibodies against neurotrophic factors. Other significant approaches include methods that improve quality of life, such as psychotherapy and heart rate variability biofeedback. Despite their therapeutic potential, there are several limitations to using approaches that manipulate cancer innervation in clinical practice. These limitations include impaired normal tissue function and nervous system function, as well as the problematic direct application of the therapeutic agent to the tumor site, dosage-dependent, cancer type-dependent, cancer stage-dependent, duration-dependent, and timing-dependent effects. Procedures that modify neoaxonogenesis and nerve fiber signaling appear to be a promising new therapeutic approach in oncology. However, more research is needed to better understand their effects on cancer progression. In the future, the assessment of the presence and density of nerve fibers in tumors, as well as the evaluation of approaches aimed at reducing their negative impact, could be part of personalized anticancer therapy. As part of this therapy, a fresh tumor sample would be collected from the patient to generate patient-derived organoid models to test and consider the possibility of using supportive therapy and to predict its efficacy. Based on these results, it would be possible to evaluate the applicability of nerve-fiber-targeted therapy for a given patient. This review article summarizes and describes the current knowledge concerning the significance of nerve fibers in cancer progression, with a particular emphasis on neoaxonogenesis in tumors and the various factors that influence this process. Full article

Although neurons are not productively infected by HIV-1, the envelope glycoprotein gp120, detectable in cerebrospinal fluid independently of active viral replication, gains intraneuronal access via lipid raft-mediated endocytosis, macropinocytosis, and retrograde axonal transport, contributing to persistent neurobiological dysfunction within the central nervous system. Once internalized, gp120 is associated with neuronal dysfunction involving convergent pathways, including excitotoxic calcium dysregulation, mitochondrial and metabolic failure, and inflammatory and senescence-associated amplification. These pathways converge on suppression of CREB and BDNF signaling, dismantling the transcriptional and neurotrophic programs required for synaptic maintenance and cognitive resilience. Extracellular vesicle-mediated dissemination and microRNA reprogramming extend gp120-associated neurobiological effects beyond sites of receptor engagement, while gut-derived metabolites, particularly quinolinic acid, lower the excitotoxic threshold through synergistic activation of NMDA receptors. Together, these mechanisms define HAND as a network disorder in which gp120 contributes to persistent neurocognitive dysfunction beyond active viral replication, identifying convergent therapeutic nodes where combination strategies targeting excitotoxicity, mitochondrial dysfunction, and neuroinflammation offer the most promising path toward durable neuroprotection. Full article

Intranasal administration is a promising drug delivery route enabling precise and rapid central nervous system targeting. In our previous work, twelve hybrid colloidal dispersions were developed, consisting of synthetic poly(ethylene-oxide)-b-poly(ε-caprolactone) (PEO-b-PCL) block copolymers with an increasing proportion of the hydrophobic PCL segment, Tween 80 (Tw80) and β-cyclodextrin derivatives (βCD), either methyl-β-CD (MβCD) or hydroxy-propyl-β-CD (HPβCD) for IN delivery of ropinirole hydrochloride (RH). Colloidal dispersions were prepared at different weight ratios (system/RH equal to 10:1 and 10:5), characterized and evaluated in vitro. The aim of this study is to evaluate the ex vivo permeation through rabbit nasal mucosa and determine the pharmacokinetic parameters of RH, when administered intranasally as a colloidal dispersion, compared with oral and intranasal RH solutions in C57BL/6J mice. Ex vivo permeation studies showed that all formulations significantly enhanced RH permeation compared to the pure RH solution (0.5 mg/mL, pH 5.6). Among them, F4 [(PEO-b-PCL₁/Tw80/HPβCD)/RH 10:5] was selected for further investigation. Pharmacokinetic analysis showed that F4 significantly enhanced both systemic and brain exposure of RH, achieving higher serum AUC and C_max values, despite a 3-fold lower administered dose compared to the oral dose. It showed high systemic (F_rel(Serum) = 1815%) and brain (F_rel(Brain) = 363%) relative bioavailability compared with oral administration, underscoring its potential as an intranasal delivery system for efficient CNS targeting. Full article

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder classically defined by cerebral amyloid-β (Aβ) plaque deposition and tau pathology. In recent years, AD has increasingly been recognized as a multisystem disorder rather than a purely brain-restricted condition, as mounting evidence indicates that Aβ metabolism is a dynamic, bidirectional process involving both central and peripheral compartments. Peripheral tissues, particularly platelets, liver, kidneys, and the gastrointestinal tract, contribute substantially to circulating Aβ levels and influence cerebral amyloid burden. Platelets are now considered the predominant source of peripheral Aβ, accounting for the majority of plasma Aβ under physiological and pathological conditions, while the liver and kidneys play critical roles in Aβ clearance through receptor-mediated uptake, enzymatic degradation and excretion. Disruption of these peripheral clearance pathways elevates circulating Aβ, increasing its transport into the brain via blood–brain barrier (BBB) mechanisms by enhanced RAGE-mediated influx and impaired LRP1-dependent efflux in AD. Peripheral Aβ entry into the central nervous system exacerbates neuroinflammation, mitochondrial dysfunction, and oxidative stress, thereby accelerating neuronal damage and disease progression. This review synthesizes updated evidence on peripheral sources of Aβ, differences between central and peripheral Aβ pools, mechanisms of Aβ transport across the BBB, pathological consequences of peripheral Aβ on the brain and emerging therapeutic strategies targeting peripheral Aβ metabolism, highlighting the importance of a systemic perspective in AD pathogenesis and treatment. Full article

Epstein–Barr virus (EBV)-positive primary central nervous system lymphoma (PCNSL) is a rare entity typically associated with profound immunosuppression, most commonly in transplant recipients or individuals with HIV. We report a case of EBV-positive PCNSL arising in a 75-year-old male with myasthenia gravis receiving chronic mycophenolate mofetil (MMF) therapy outside the transplant setting. The patient presented with progressive neurological deficits, and brain magnetic resonance imaging demonstrated multiple enhancing lesions. Stereotactic biopsy revealed diffuse large B-cell lymphoma of non–germinal center subtype with immunoblastic features and EBV-encoded RNA (EBER) positivity, confirming EBV-positive PCNSL. MMF was discontinued, and the patient was treated with rituximab and high-dose methotrexate, resulting in stable disease. This case highlights that prolonged MMF therapy may confer sufficient immunosuppression to permit EBV-driven lymphoproliferative disease even in non-transplant patients. Early recognition, withdrawal of immunosuppression, and initiation of methotrexate-based chemotherapy can lead to favorable outcomes. Full article

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system with onset typically in early adulthood and the potential for long-term disability. Current therapies are initiated after symptom onset and do not address early disease triggers, highlighting the need for preventive strategies. Epstein–Barr virus (EBV) infection has emerged as the strongest candidate upstream factor in MS development. This narrative review provides a focused and critical synthesis of current evidence, with particular emphasis on the prevention perspective and the conceptual framing of MS as a potentially infection-driven disease. We integrate epidemiological, immunological, and mechanistic data while explicitly addressing key uncertainties and limitations in causal interpretation. Longitudinal studies indicate that EBV infection precedes MS onset in most cases and is associated with a markedly increased risk following seroconversion. However, EBV infection alone is not sufficient to cause MS. Proposed mechanisms include immune dysregulation and molecular mimicry, though key uncertainties remain. Based on current evidence, EBV represents a promising but unproven target for MS prevention. Future strategies may include prevention of EBV infection or infectious mononucleosis, alongside improved risk stratification and long-term studies to assess the impact of EBV-targeted interventions on MS incidence. Full article