Search Results (31)

Cardiomyopathies affect over 3 million individuals globally, with conventional treatments exhibiting up to 60% resistance and 25% 30-day readmission rates. This review synthesizes the current evidence on the role of neuro-immune interactions in the pathogenesis of cardiomyopathy and evaluates emerging therapies targeting this axis. We systematically examined clinical trials and mechanistic and multi-omics data across cardiomyopathy phenotypes, focusing on autonomic-immune dysregulation. Sympathetic overactivation, present in approximately 85% of patients, correlates with elevated pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) and contributes significantly to therapeutic non-response. Concurrent parasympathetic withdrawal impairs cholinergic anti-inflammatory pathways, as reflected by reduced heart rate variability and baroreflex sensitivity. At the molecular level, shared mechanisms include inflammasome activation, neuroimmune synaptic signaling, and neurogenic inflammation. Emerging therapies targeting this axis are promising. Vagus nerve stimulation, as demonstrated in the INOVATE-HF trial, improves functional outcomes, whereas IL-1β antagonists reduce cardiovascular events by 15–20% in the context of inflammatory diseases. Bioelectronic interventions, such as transcutaneous vagal nerve stimulation and baroreflex activation therapy, offer noninvasive dual-modulatory strategies that address both neural and immune pathways, positioning the neuroimmune axis as a central driver of cardiomyopathy, regardless of etiology. The integration of genetic and metabolomic profiling may enable precision therapies targeting neuroimmune circuits, thereby overcoming the limitations of hemodynamic-focused care. This mechanistic framework shifts the therapeutic paradigm from symptomatic relief to targeted modulation of pathogenic pathways, with implications for millions of patients with cardiomyopathy and broader inflammatory cardiovascular disorders. Full article

Acute transverse myelitis (ATM) is a rare, immune-mediated disorder of the spinal cord characterized by sensory, motor, and autonomic dysfunction. Although the human papillomavirus (HPV) vaccine is widely regarded as safe, isolated reports have suggested a potential temporal association with autoimmune neurological events, including ATM. We present a case of a 21-year-old woman who developed ATM two weeks following administration of the first dose of the HPV vaccine (Cervarix). The clinical presentation included rapid-onset paraparesis, sensory deficits, and sphincter dysfunction. An MRI revealed a T2-hyperintense lesion at the Th10–Th12 level. A cerebrospinal fluid analysis showed elevated protein levels. The patient underwent corticosteroid therapy, plasmapheresis, and IVIG, followed by a comprehensive, individualized rehabilitation program. This included balance and stability training, Redcord-based neuromuscular activation, electrostimulation, and pelvic floor therapy. Although no causal link between HPV vaccination and ATM has been established, this case emphasizes the importance of considering post-vaccinal autoimmune phenomena. More importantly, it illustrates the critical role of early, targeted rehabilitation—particularly pelvic floor re-education and neuromodulation—in improving outcomes in patients with significant motor and autonomic deficits. Full article

Spinal cord injury (SCI) results in a significant loss of motor, sensory, and autonomic function, imposing substantial biosocial and economic burdens. Traditional approaches, such as stem cell therapy and immune modulation, have faced translational challenges, whereas neuromodulation and digital brain–spinal cord interfaces combining brain–computer interface (BCI) technology and epidural spinal cord stimulation (ESCS) to create brain–spine interfaces (BSIs) offer promising alternatives by leveraging residual neural pathways to restore physiological function. This review examines recent advancements in neuromodulation, focusing on the future translation of clinical trial data to clinical practice. We address key considerations, including scalability, patient selection, surgical techniques, postoperative rehabilitation, and ethical implications. By integrating interdisciplinary collaboration, standardized protocols, and patient-centered design, neuromodulation has the potential to revolutionize SCI rehabilitation, reducing long-term disability and enhancing quality of life globally. Full article

Traumatic brain injury (TBI) remains a critical global health issue with limited effective treatments. Traditional care of TBI patients focuses on stabilization and symptom management without regenerating damaged brain tissue. In this review, we analyze the current state of treatment of TBI, with focus on novel therapeutic approaches aimed at reducing secondary brain injury and promoting recovery. There are few innovative strategies that break away from the traditional, biological target-focused treatment approaches. Precision medicine includes personalized treatments based on biomarkers, genetics, advanced imaging, and artificial intelligence tools for prognosis and monitoring. Stem cell therapies are used to repair tissue, regulate immune responses, and support neural regeneration, with ongoing development in gene-enhanced approaches. Nanomedicine uses nanomaterials for targeted drug delivery, neuroprotection, and diagnostics by crossing the blood–brain barrier. Brain–machine interfaces enable brain-device communication to restore lost motor or neurological functions, while virtual rehabilitation and neuromodulation use virtual and augmented reality as well as brain stimulation techniques to improve rehabilitation outcomes. While these approaches show great potential, most are still in development and require more clinical testing to confirm safety and effectiveness. The future of TBI therapy looks promising, with innovative strategies likely to transform care. Full article

Resiniferatoxin (RTX), a potent capsaicin analog, is being investigated as a therapeutic agent for neurogenic conditions, particularly those affecting bladder control. However, the transcriptomic effects of RTX on the urinary bladder remain largely unexplored. This study aimed to characterize the transcriptomic changes in the porcine urinary bladder trigone region removed seven days post-treatment with intravesical RTX administration (500 nmol per animal in 60 mL of 5% aqueous solution of ethyl alcohol). High-throughput sequencing identified 126 differentially expressed genes (DEGs; 66 downregulated, 60 upregulated), 5 differentially expressed long non-coding RNAs (DELs), and 22 other RNAs, collectively involved in 175 gene ontology (GO) processes. Additionally, differential alternative splicing events (DASes) and single nucleotide variants (SNVs) were detected. RTX significantly modulated signaling pathways related to nerve growth and myelination. Changes in genes associated with synaptic plasticity and neuromodulation were observed, particularly within serotoninergic and cholinergic signaling. RTX altered the expression of immune-related genes, particularly those involved in chemokine signaling and immune regulation. Notably, altered gene expression patterns suggest a potential anti-cancer role for RTX. These findings provide new insights into RTX’s therapeutic effects beyond TRPV1 receptor interactions, filling a critical gap in our understanding of its molecular impact on bladder tissue. Full article

Aging is associated with a decline in physiological performance leading to increased inflammation and impaired immune function. Polysaccharides (PLs) found in plants, fruits, and fungi are emerging as potential targets for therapeutic intervention, but little is known about their effects on chronic inflammation and aging. This review aims to highlight the current advances related to the use of PLs, with the presence of arabinose, to attenuate oxidative stress and chronic and acute inflammation, and their immunomodulatory effects associated with antioxidant status in monocytes, macrophages, and neutrophil infiltration, and leukocyte rolling adhesion in neutrophils. In addition, recent studies have shown the importance of investigating the ‘major’ monosaccharide, such as arabinose, present in several of these polysaccharides, and with described effects on gut microbiome, glucose, inflammation, allergy, cancer cell proliferation, neuromodulation, and metabolic stress. Perspectives and opportunities for further investigation are provided. By promoting a balanced immune response and reducing inflammation, PLs with arabinose or even arabinose per se may alleviate the immune dysregulation and inflammation seen in the elderly, therefore providing a promising strategy to mitigate a variety of diseases. Full article

Background/Objectives: Complex regional pain syndrome (CRPS) is characterized by severe pain and reduced functionality, which can significantly affect an individual’s quality of life. The current treatment of CRPS is challenging. However, recent advances in diagnostic and treatment methods show promise for improving patient outcomes. This review aims to place the question of CRPS in a broader context and highlight the objectives of the research for future directions in the management of CRPS. Methods: This study involved a comprehensive literature review. Results: Research has identified three primary pathophysiological pathways that may explain the clinical variability observed in CRPS: inflammatory mechanisms, vasomotor dysfunction, and maladaptive neuroplasticity. Investigations into these pathways have spurred the development of novel diagnostic and treatment strategies focused on N-Methyl-D-aspartate Receptor Antagonists (NMDA), Toll-like receptor 4 (TLR-4), α1 and α2 adrenoreceptors, as well as the identification of microRNA (miRNA) biomarkers. Treatment methods being explored include immune and glial-modulating agents, intravenous immunoglobulin (IVIG) therapy, plasma exchange therapy, and neuromodulation techniques. Additionally, there is ongoing debate regarding the efficacy of other treatments, such as free radical scavengers, alpha-lipoic acid (ALA), dimethyl fumarate (DMF), adenosine monophosphate-activated protein kinase (AMPK) activators such as metformin, and phosphodiesterase-5 inhibitors such as tadalafil. Conclusions: The controversies surrounding the mechanisms, diagnosis, and treatment of CRPS have prompted researchers to investigate new approaches aimed at enhancing understanding and management of the condition, with the goal of alleviating symptoms and reducing associated disabilities. Full article

Chronic pain is a multidimensional experience that not only involves persistent nociception but is also frequently accompanied by significant emotional disorders, such as anxiety and depression, which complicate its management and amplify its impact. This review provides an in-depth exploration of the neurobiological mechanisms underlying the comorbidity of chronic pain and emotional disturbances. Key areas of focus include the dysregulation of major neurotransmitter systems (serotonin, gamma-aminobutyric acid, and glutamate) and the resulting functional remodeling of critical neural circuits implicated in pain processing, emotional regulation, and reward. Given the contribution of neuroimmune mechanisms to pain chronicity and mood disorders, we further conducted an in-depth investigation into the role of neuroimmune factors, including resident immune cells, infiltrating immune cells, and the release of inflammatory mediators. This review further discusses current therapeutic strategies, encompassing pharmacological interventions, neuromodulation, and integrative approaches, and emphasizes the necessity of targeted treatments that address both pain and emotional components. Finally, it identifies gaps in the current understanding and outlines future research directions aimed at elucidating the complex interplay between chronic pain and emotional disorders, thereby laying the foundation for more effective and holistic treatment paradigms. Full article

Historically, the multiple uses of cannabis as a medicine, food, and for recreational purposes as a psychoactive drug span several centuries. The various components of the plant (i.e., seeds, roots, leaves and flowers) have been utilized to alleviate symptoms of inflammation and pain (e.g., osteoarthritis, rheumatoid arthritis), mood disorders such as anxiety, and intestinal problems such as nausea, vomiting, abdominal pain and diarrhea. It has been established that the intestinal microbiota progresses neurological, endocrine, and immunological network effects through the gut–microbiota–brain axis, serving as a bilateral communication pathway between the central and enteric nervous systems. An expanding body of clinical evidence emphasizes that the endocannabinoid system has a fundamental connection in regulating immune responses. This is exemplified by its pivotal role in intestinal metabolic and immunity equilibrium and intestinal barrier integrity. This neuromodulator system responds to internal and external environmental signals while also serving as a homeostatic effector system, participating in a reciprocal association with the intestinal microbiota. We advance an exogenous cannabinoid–intestinal microbiota–endocannabinoid system axis potentiated by the intestinal microbiome and medicinal cannabinoids supporting the mechanism of action of the endocannabinoid system. An integrative medicine model of patient care is advanced that may provide patients with beneficial health outcomes when prescribed medicinal cannabis. Full article

Fibromyalgia (FM) is a disorder characterized by widespread chronic pain, significant depression, and various neural abnormalities. Recent research suggests a reciprocal exacerbation mechanism between chronic pain and depression. In patients with FM, dysregulation of tryptophan (Trp) metabolism has been identified. Trp, an essential amino acid, serves as a precursor to serotonin (5-HT), a neuromodulator that influences mood, appetite, sleep, and pain perception through the receptors 5-HT1, 5-HT2, and 5-HT3. Additionally, Trp is involved in the kynurenine pathway, a critical route in the immune response, inflammation, and production of neuroactive substances and nicotinamide adenine dinucleotide (NAD+). The activation of this pathway by pro-inflammatory cytokines, such as tumor necrosis factor α (TNF-α) and interferon gamma (IFN-γ), leads to the production of kynurenic acid (KYNA), which has neuroprotective properties, and quinolinic acid (QA), which is neurotoxic. These findings underscore the crucial balance between Trp metabolism, 5-HT, and kynurenine, where an imbalance can contribute to the dual burden of pain and depression in patients with FM. This review proposes a novel therapeutic approach for FM pain management, focusing on inhibiting QA synthesis while co-administering selective serotonin reuptake inhibitors to potentially increase KYNA levels, thus dampening pain perception and improving patient outcomes. Full article

The research in neuroimmunomodulation aims to shed light on the complex relationships that exist between the immune and neurological systems and how they affect the human body. This multidisciplinary field focuses on the way immune responses are influenced by brain activity and how neural function is impacted by immunological signaling. This provides important insights into a range of medical disorders. Targeting both brain and immunological pathways, neuroimmunomodulatory approaches are used in clinical pain management to address chronic pain. Pharmacological therapies aim to modulate neuroimmune interactions and reduce inflammation. Furthermore, bioelectronic techniques like vagus nerve stimulation offer non-invasive control of these systems, while neuromodulation techniques like transcranial magnetic stimulation modify immunological and neuronal responses to reduce pain. Within the context of aging, neuroimmunomodulation analyzes the ways in which immunological and neurological alterations brought on by aging contribute to cognitive decline and neurodegenerative illnesses. Restoring neuroimmune homeostasis through strategies shows promise in reducing age-related cognitive decline. Research into mood disorders focuses on how immunological dysregulation relates to illnesses including anxiety and depression. Immune system fluctuations are increasingly recognized for their impact on brain function, leading to novel treatments that target these interactions. This review emphasizes how interdisciplinary cooperation and continuous research are necessary to better understand the complex relationship between the neurological and immune systems. Full article

In the realm of gastroenterology, the inadequacy of current medical treatments for gastrointestinal (GI) motility disorders and inflammatory bowel disease (IBD), coupled with their potential side effects, necessitates novel therapeutic approaches. Neuromodulation, targeting the nervous system’s control of GI functions, emerges as a promising alternative. This review explores the promising effects of vagal nerve stimulation (VNS), magnetic neuromodulation, and acupuncture in managing these challenging conditions. VNS offers targeted modulation of GI motility and inflammation, presenting a potential solution for patients not fully relieved from traditional medications. Magnetic neuromodulation, through non-invasive means, aims to enhance neurophysiological processes, showing promise in improving GI function and reducing inflammation. Acupuncture and electroacupuncture, grounded in traditional medicine yet validated by modern science, exert comprehensive effects on GI physiology via neuro-immune-endocrine mechanisms, offering relief from motility and inflammatory symptoms. This review highlights the need for further research to refine these interventions, emphasizing their prospective role in advancing patient-specific management strategies for GI motility disorders and IBD, thus paving the way for a new therapeutic paradigm. Full article

Xiaochaihu granules (XCHG) are extensively used to treat fever. Nevertheless, the underlying mechanism remains elusive. This study aimed to explore the potential of XCHG in mitigating yeast-induced fever and the underlying metabolic pathways. The chemical composition of XCHG was ascertained using ultra-fast liquid chromatography/quadrupole-time-of-flight tandem mass spectrometry (UFLC-Q-TOF-MS/MS), followed by integrated network analysis to predict potential targets. We then conducted experimental validation using pharmacological assays and metabolomics analysis in a yeast-induced mouse fever model. The study identified 133 compounds in XCHG, resulting in the development of a comprehensive network of herb–compound–biological functional modules. Subsequently, molecular dynamic (MD) simulations confirmed the stability of the complexes, including γ-aminobutyric acid B receptor 2 (GABBR2)–saikosaponin C, prostaglandin endoperoxide synthases (PTGS2)–lobetyolin, and NF-κB inhibitor IκBα (NFKBIA)–glycyrrhizic acid. Animal experiments demonstrated that XCHG reduced yeast-induced elevation in NFKBIA’s downstream regulators [interleukin (IL)-1β and IL-8], inhibited PTGS2 activity, and consequently decreased prostaglandin E2 (PGE2) levels. XCHG also downregulated the levels of 5-hydroxytryptamine (5-HT), γ-aminobutyric acid (GABA), corticotropin releasing hormone (CRH), and adrenocorticotrophin (ACTH). These corroborated the network analysis results indicating XCHG’s effectiveness against fever in targeting NFKBIA, PTGS2, and GABBR2. The hypothalamus metabolomics analysis identified 14 distinct metabolites as potential antipyretic biomarkers of XCHG. In conclusion, our findings suggest that XCHG alleviates yeast-induced fever by regulating inflammation/immune responses, neuromodulation, and metabolism modules, providing a scientific basis for the anti-inflammatory and antipyretic properties of XCHG. Full article

In the era of a steadily increasing lifespan, neurodegenerative diseases among the elderly present a significant therapeutic and socio-economic challenge. A properly balanced diet and microbiome diversity have been receiving increasing attention as targets for therapeutic interventions in neurodegeneration. Microbiota may affect cognitive function, neuronal survival and death, and gut dysbiosis was identified in Parkinson’s disease (PD). Tryptophan (Trp), an essential amino acid, is degraded by microbiota and hosts numerous compounds with immune- and neuromodulating properties. This broad narrative review presents data supporting the concept that microbiota, the Trp-kynurenine (KYN) pathway and aryl hydrocarbon receptors (AhRs) form a triad involved in PD. A disturbed gut–brain axis allows the bidirectional spread of pro-inflammatory molecules and α-synuclein, which may contribute to the development/progression of the disease. We suggest that the peripheral levels of kynurenines and AhR ligands are strongly linked to the Trp metabolism in the gut and should be studied together with the composition of the microbiota. Such an approach can clearly delineate the sub-populations of PD patients manifesting with a disturbed microbiota–Trp-KYN–brain triad, who would benefit from modifications in the Trp metabolism. Analyses of the microbiome, Trp-KYN pathway metabolites and AhR signaling may shed light on the mechanisms of intestinal distress and identify new targets for the diagnosis and treatment in early-stage PD. Therapeutic interventions based on the combination of a well-defined food regimen, Trp and probiotics seem of potential benefit and require further experimental and clinical research. Full article

Lyme disease, the most common tick-borne disease in the United States, is caused by infection with the spirochete Borrelia burgdorferi. While most patients with acute Lyme disease recover completely if treated with antibiotics shortly after the onset of infection, approximately 10–30% experience post-treatment symptoms and 5–10% have residual symptoms with functional impairment (post-treatment Lyme disease syndrome or PTLDS). These patients typically experience pain, cognitive problems, and/or fatigue. This narrative review provides a broad overview of Lyme disease, focusing on neuropsychiatric manifestations and persistent symptoms. While the etiology of persistent symptoms remains incompletely understood, potential explanations include persistent infection, altered neural activation, and immune dysregulation. Widely recognized is that new treatment options are needed for people who have symptoms that persist despite prior antibiotic therapy. After a brief discussion of treatment approaches, the article focuses on vagus nerve stimulation (VNS), a neuromodulation approach that is FDA-approved for depression, epilepsy, and headache syndromes and has been reported to be helpful for other diseases characterized by inflammation and neural dysregulation. Transcutaneous VNS stimulates the external branch of the vagus nerve, is minimally invasive, and is well-tolerated in other conditions with few side effects. If well-controlled double-blinded studies demonstrate that transcutaneous auricular VNS helps patients with chronic syndromes such as persistent symptoms after Lyme disease, taVNS will be a welcome addition to the treatment options for these patients. Full article