Search Results (56)

Hydrogen-rich water (HRW) has shown neuroprotective effects in acute brain injury, but its role in chronic radiation-induced brain injury (RIBI) remains unclear. This study investigated the long-term efficacy of HRW in mitigating cognitive impairment and neuronal damage caused by chronic RIBI. Fifty male Sprague Dawley rats were randomly divided into five groups: control, irradiation (IR), IR with memantine, IR with HRW, and IR with combined treatment. All but the control group received 20 Gy whole-brain X-ray irradiation, followed by daily interventions for 60 days. Behavioral assessments, histopathological analyses, oxidative stress measurements, ¹⁸F-FDG PET/CT imaging, transcriptomic sequencing, RT-qPCR, Western blot, and serum ELISA were performed. HRW significantly improved anxiety-like behavior, memory, and learning performance compared to the IR group. Histological results revealed that HRW reduced neuronal swelling, degeneration, and loss and enhanced dendritic spine density and neurogenesis. PET/CT imaging showed increased hippocampal glucose uptake in the IR group, which was alleviated by HRW treatment. Transcriptomic and molecular analyses indicated that HRW modulated key genes and proteins, including CD44, CD74, SPP1, and Wnt1, potentially through the MIF, Wnt, and SPP1 signaling pathways. Serum CD44 levels were also lower in treated rats, suggesting its potential as a biomarker for chronic RIBI. These findings demonstrate that HRW can alleviate chronic RIBI by preserving neuronal structure, reducing inflammation, and enhancing neuroplasticity, supporting its potential as a therapeutic strategy for radiation-induced cognitive impairment. Full article

Introduction: Substance use disorders (SUDs) pose a significant public health challenge, with current treatments often exhibiting limited effectiveness and high relapse rates. Transcranial direct current stimulation (tDCS), a noninvasive neuromodulation technique that delivers low-intensity direct current via scalp electrodes, has shown promise in various psychiatric and neurological conditions. In SUDs, tDCS may help to modulate key neurocircuits involved in craving, executive control, and reward processing, potentially mitigating compulsive drug use. However, the precise neurobiological mechanisms by which tDCS exerts its therapeutic effects in SUDs remain only partly understood. This review addresses that gap by synthesizing evidence from clinical studies that used neuroimaging (fMRI, fNIRS, EEG) and blood-based biomarkers to elucidate tDCS’s mechanisms in treating SUDs. Methods: A targeted literature search identified articles published between 2008 and 2024 investigating tDCS interventions in alcohol, nicotine, opioid, and stimulant use disorders, focusing specifically on physiological and neurobiological assessments rather than purely behavioral outcomes. Studies were included if they employed either neuroimaging (fMRI, fNIRS, EEG) or blood tests (neurotrophic and neuroinflammatory markers) to investigate changes induced by single- or multi-session tDCS. Two reviewers screened titles/abstracts, conducted full-text assessments, and extracted key data on participant characteristics, tDCS protocols, neurobiological measures, and clinical outcomes. Results: Twenty-seven studies met the inclusion criteria. Across fMRI studies, tDCS—especially targeting the dorsolateral prefrontal cortex—consistently modulated large-scale network activity and connectivity in the default mode, salience, and executive control networks. Many of these changes correlated with subjective craving, attentional bias, or extended time to relapse. EEG-based investigations found that tDCS can alter event-related potentials (e.g., P3, N2, LPP) linked to inhibitory control and salience processing, often preceding or accompanying changes in craving. One fNIRS study revealed enhanced connectivity in prefrontal regions under active tDCS. At the same time, two blood-based investigations reported the partial normalization of neurotrophic (BDNF) and proinflammatory markers (TNF-α, IL-6) in participants receiving tDCS. Multi-session protocols were more apt to drive clinically meaningful neuroplastic changes than single-session interventions. Conclusions: Although significant questions remain regarding optimal stimulation parameters, sample heterogeneity, and the translation of acute neural shifts into lasting behavioral benefits, this research confirms that tDCS can induce detectable neurobiological effects in SUD populations. By reshaping activity across prefrontal and reward-related circuits, modulating electrophysiological indices, and altering relevant biomarkers, tDCS holds promise as a viable, mechanism-based adjunctive therapy for SUDs. Rigorous, large-scale studies with longer follow-up durations and attention to individual differences will be essential to establish how best to harness these neuromodulatory effects for durable clinical outcomes. Full article

Anxiety and depression are highly prevalent mental health disorders often associated with dysregulation of neuroendocrine and immune systems, particularly the hypothalamic–pituitary–adrenal (HPA) axis and the sympathetic–adrenal–medullary (SAM) system. Recent research highlights the potential of salivary biomarkers to serve as non-invasive indicators for psychological distress. This narrative review synthesizes current evidence on key salivary biomarkers, cortisol, alpha-amylase (sAA), secretory immunoglobulin A (sIgA), chromogranin A (CgA), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), brain-derived neurotrophic factor (BDNF), and salivary microRNAs (miRNAs), in relation to anxiety, depression, and stress. A comprehensive literature search (2010–2025) was conducted using multiple databases and relevant MeSH terms. The review reveals consistent associations between these salivary analytes and stress-related disorders, reflecting changes in neuroendocrine activity, immune response, and neuroplasticity. Cortisol and sAA mirror acute stress reactivity, while cytokines and CRP indicate chronic inflammation. BDNF and miRNAs provide insight into neuroplastic dysfunction and gene regulation. Despite promising results, limitations such as variability in sampling methods and biomarker specificity remain. In conclusion, salivary biomarkers offer a promising avenue for early detection, monitoring, and personalization of treatment in mood and anxiety disorders. Conclusions: Cortisol and alpha-amylase serve as the principal markers of acute stress response, whereas cytokines such as IL-6 and TNF-α, together with CRP, indicate chronic inflammation associated with extended emotional distress. Full article

Background/Objectives: Child abuse is a pervasive global issue with significant implications for the physical, emotional, and psychological well-being of victims. This review highlights the clinical, molecular, and therapeutic dimensions of child abuse, emphasizing its long-term impact and the need for interdisciplinary approaches. Early exposure to abuse activates the hypothalamic-pituitary-adrenal (HPA) axis, leading to chronic cortisol release and subsequent neuroplastic changes in brain regions such as the hippocampus, amygdala, and prefrontal cortex. These molecular alterations, including epigenetic modifications and inflammatory responses, contribute to the heightened risk of psychiatric disorders and chronic illnesses in survivors. Clinically, child abuse presents with diverse manifestations ranging from physical injuries to psychological and developmental disorders, making timely diagnosis challenging. Methods: A multidisciplinary approach involving thorough clinical evaluation, detailed histories, and collaboration with child protection services is essential for accurate diagnosis and effective intervention. Results: Recent advances in molecular biology have identified biomarkers, such as stress-related hormones and epigenetic changes, which provide novel insights into the physiological impact of abuse and potential targets for therapeutic intervention. Current treatment strategies prioritize the child’s safety, psychological well-being, and prevention of further abuse. Trauma-focused cognitive behavioral therapy and family-centered interventions are pivotal in promoting recovery and resilience. Conclusions: Emerging research focuses on integrating molecular findings with clinical practice, utilizing digital health tools, and leveraging big data to develop predictive models and personalized treatments. Interdisciplinary collaboration remains crucial to translating research into policy and practice, ultimately aiming to mitigate the impact of child abuse and improve outcomes for survivors. Full article

Background/Objectives: Mild Cognitive Impairment (MCI) represents a clinical syndrome characterized by cognitive decline greater than expected for an individual’s age and education level but not severe enough to significantly interfere with daily activities, with variable trajectories that may remain stable, progress to dementia, or occasionally revert to normal cognition. This systematic review examines neurotechnological approaches to cognitive rehabilitation in MCI populations, including neuromodulation, electroencephalography (EEG), virtual reality (VR), cognitive training, physical exercise, and artificial intelligence (AI) applications. Methods: A systematic review following PRISMA guidelines was conducted on 34 empirical studies published between 2014 and 2024. Studies were identified through comprehensive database searches and included if they employed neurotechnological interventions targeting cognitive outcomes in individuals with MCI. Results: Evidence indicates promising outcomes across multiple intervention types. Neuromodulation techniques showed beneficial effects on memory and executive function. EEG analyses identified characteristic neurophysiological markers of MCI with potential for early detection and monitoring. Virtual reality enhanced assessment sensitivity and rehabilitation engagement through ecologically valid environments. Cognitive training demonstrated the most excellent efficacy with multi-domain, adaptive approaches. Physical exercise interventions yielded improvements through multiple neurobiological pathways. Emerging AI applications showed potential for personalized assessment and intervention through predictive modeling and adaptive algorithms. Conclusions: Neurotechnological approaches offer promising avenues for MCI rehabilitation, with the most substantial evidence for integrated interventions targeting multiple mechanisms. Neurophysiological monitoring provides valuable biomarkers for diagnosis and treatment response. Future research should focus on more extensive clinical trials, standardized protocols, and accessible implementation models to translate these technological advances into clinical practice. Full article

Purpose: Obesity’s metabolic consequences are well documented; however, its neurobiological underpinnings remain elusive. This systematic review addresses a critical gap by synthesizing evidence on obesity-induced neuroplasticity across structural, functional, and molecular domains through advanced neuroimaging. Methods: According to PRISMA guidelines, we systematically searched (2015–2024) across PubMed/Web of Science, employing MeSH terms: (“Obesity” [Majr]) AND (“Neuroimaging” [Mesh] OR “Magnetic Resonance Imaging” [Mesh]). A total of 104 studies met the inclusion criteria. The inclusion criteria required the following: (1) multimodal imaging protocols (structural MRI/diffusion tensor imaging/resting-state functional magnetic resonance imaging (fMRI)/positron emission tomography (PET)); (2) pre-/post-intervention longitudinal design. Risk of bias was assessed via the Newcastle-Ottawa Scale. Key Findings: 1. Structural alterations: 7.2% mean gray matter reduction in prefrontal cortex (Cohen’s d = 0.81). White matter integrity decline (FA reduction β = −0.33, p < 0.001) across 12 major tracts. 2. Functional connectivity: Resting-state hyperactivity in mesolimbic pathways (fALFF + 23%, p-FDR < 0.05). Impaired fronto–striatal connectivity (r = −0.58 with BMI, 95% CI [−0.67, −0.49]). 3. Interventional reversibility: Bariatric surgery restored prefrontal activation (Δ = +18% vs. controls, p = 0.002). Neurostimulation (transcranial direct current stimulation (tDCS) enhanced cognitive control (post-treatment β = 0.42, p = 0.009). Conclusion: 1. Obesity induces multidomain neural reorganization beyond traditional reward circuits. 2. Neuroimaging biomarkers (e.g., striatal PET-dopamine binding potential) predict intervention outcomes (AUC = 0.79). 3. Precision neuromodulation requires tripartite integration of structural guidance, functional monitoring, and molecular profiling. Findings highlight neuroimaging’s pivotal role in developing stage-specific therapeutic strategies. Full article

Post-traumatic stress disorder (PTSD) is a complex psychiatric condition characterized by persistent behavioral and neurobiological alterations following trauma. Although rodent models are commonly used to study PTSD, zebrafish (Danio rerio) have emerged as a promising alternative due to their genetic similarity to humans, conserved stress response systems, and high-throughput capabilities. This systematic review evaluates 33 experimental studies on zebrafish PTSD models, focusing on behavioral, neurochemical, and molecular outcomes. Chronic unpredictable stress (CUS/UCS) paradigms of 14–15 days were identified as the most reliable for inducing PTSD-like phenotypes, consistently resulting in anxiety-like behaviors, cortisol dysregulation, and gene expression changes. In contrast, acute stress models produced transient effects, and social defeat paradigms showed methodological variability. Chronic models frequently demonstrated neurotransmitter imbalances, oxidative stress, and upregulation of inflammatory and neuroplasticity-related genes. However, the literature revealed challenges, including protocol heterogeneity, limited sex-specific analyses, and constraints in longitudinal biomarker tracking. Future directions include epigenetic profiling, environmental standardization, and cross-species validation. When used with methodological rigor, zebrafish offer a powerful and translationally relevant platform to study PTSD mechanisms and screen novel interventions. Full article

Background/Objectives: Lower-limb amputation (LLA) leads to disability, impaired mobility, and reduced quality of life, affecting 1.6 million people in the USA. Post-amputation, motor cortex reorganization occurs, contributing to phantom limb pain (PLP). Transcranial magnetic stimulation (TMS) assesses changes in cortical excitability, helping to identify compensatory mechanisms. This study investigated the association between TMS metrics and clinical and neurophysiological outcomes in LLA patients. Methods: A cross-sectional analysis of the DEFINE cohort, with 59 participants, was carried out. TMS metrics included resting motor threshold (rMT), motor-evoked potential (MEP) amplitude, short intracortical inhibition (SICI), and intracortical facilitation (ICF). Results: Multivariate analysis revealed increased ICF and rMT in the affected hemisphere of PLP patients, while SICI was reduced with the presence of PLP. A positive correlation between SICI and EEG theta oscillations in the frontal, central, and parietal regions suggested compensatory mechanisms in the unaffected hemisphere. Increased MEP was associated with reduced functional independence. Conclusions: SICI appears to be a key factor linked to the presence of PLP, but not its intensity. Reduced SICI may indicate impaired cortical compensation, contributing to PLP. Other neural mechanisms, including central sensitization and altered thalamocortical connectivity, may influence PLP’s severity. Our findings align with those of prior studies, reinforcing low SICI as a marker of maladaptive neuroplasticity in amputation-related pain. Additionally, longer amputation duration was associated with disrupted SICI, suggesting an impact of long-term plasticity changes. Full article

Background/Objectives: Stroke often leads to persistent cognitive and emotional impairments, which rehabilitation may mitigate. However, the biological mechanisms underlying such improvements remain unclear. This study investigated whether supplementing computerized cognitive training (CCT) with mindfulness-based stress reduction (MBSR) or physical exercise (PE) modulated biomarkers of neuroplasticity, inflammation, and stress in patients with chronic stroke compared to CCT alone. We also explored whether biomarker changes mediated or correlated with behavioral improvements. Methods: In a three-arm, single-blind, randomized controlled trial (NCT04759950), 141 patients with chronic stroke were randomized (1:1:1) to MBSR+CCT, PE+CCT, or CCT-only for 12 weeks. Plasma levels of brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), C-reactive protein (CRP), interleukin-6 (IL-6), and cortisol were measured at baseline and post-intervention. Cognitive, mental health, mindfulness, and fitness outcomes were also assessed. Between- and within-group changes were analyzed using ANCOVA and paired t-tests. Per-protocol and complete-case analyses were conducted. Results: Among the 109 participants with ≥80% adherence, the only significant between-group difference was for VEGF: it remained stable in the MBSR+CCT group but declined in PE+CCT and CCT-only. Within-group analyses showed significant decreases in cortisol in MBSR+CCT and PE+CCT, while IGF-1 levels declined across all groups. In contrast, BDNF, IL-6, and CRP did not show significant changes, and biomarker changes were not significantly associated with behavioral improvements. Complete-case analysis (n = 126) yielded similar findings. Conclusions: Our findings suggest that combining MBSR or PE with CCT may modulate certain biological processes relevant to stroke recovery. MBSR may help maintain VEGF levels, which could support vascular health, while MBSR and PE may contribute to lowering cortisol levels. However, since no clear association with behavioral improvements was found, further research is needed to determine the clinical relevance of these biomarker changes in stroke recovery. Full article

Background/Objectives: Neurodegenerative diseases represent a growing global health challenge with limited therapeutic options. Physical exercise has emerged as a promising non-pharmacological intervention with potential neuroprotective effects. This narrative review examines the mechanisms through which exercise induces neuroplasticity and their implications for neurodegenerative disease prevention. Methods: We synthesized evidence from molecular, animal, and human studies on exercise-induced neuroplasticity and neurodegenerative disease prevention through a comprehensive literature review. Results: Exercise enhances neuroplasticity through multiple pathways: (1) neurotrophic signaling (BDNF, IGF-1, VEGF), (2) neuroendocrine regulation, (3) epigenetic modifications, and (4) metabolic pathway optimization. These molecular changes support structural adaptations including hippocampal neurogenesis, enhanced synaptic plasticity, improved cerebrovascular function, and optimized brain network connectivity. Exercise directly impacts pathological features of neurodegenerative diseases by reducing protein aggregation, attenuating excitotoxicity and oxidative stress, and enhancing mitochondrial function. Clinical evidence consistently demonstrates associations between physical activity and reduced neurodegenerative risk, with intervention studies supporting causal benefits on cognitive function and brain structure. Conclusions: Exercise represents a multi-target intervention addressing several pathological mechanisms simultaneously across various neurodegenerative conditions. Its accessibility, minimal side effects, and multiple health benefits position it as a promising preventive strategy. Future research should focus on understanding individual response variability, developing sensitive biomarkers, and creating personalized exercise prescriptions for optimal neuroprotection. Full article

Psychiatric disorders (PDs), including schizophrenia (SZ), major depressive disorder (MDD), bipolar disorder (BD), autism spectrum disorder (ASD), among other disorders, represent a significant global health burden. Despite advancements in understanding their biological mechanisms, there is still no reliable objective and reliable biomarker; therefore, diagnosis remains largely reliant on subjective clinical assessments. Peripheral biomarkers in plasma or serum are interesting due to their accessibility, low cost, and potential to reflect central nervous system processes. Among these, the insulin-like growth factor (IGF) family, IGF-1, IGF-2, and IGF-binding proteins (IGFBPs), has gained attention for its roles in neuroplasticity, cognition, and neuroprotection, as well as for their capability to cross the blood–brain barrier. This review evaluates the evidence for IGF family alterations in PDs, with special focus on SZ, MDD, and BD, while also addressing other PDs covering almost 40 years of history. In SZ patients, IGF-1 alterations have been linked to metabolic dysregulation, treatment response, and hypothalamic–pituitary–adrenal axis dysfunction. In MDD patients, IGF-1 appears to compensate for impaired neurogenesis, although findings are inconsistent. Emerging studies on IGF-2 and IGFBPs suggest potential roles across PDs. While promising, heterogeneity among studies and methodological limitations highlights the need for further research to validate IGFs as reliable psychiatric biomarkers. Full article

Background/Objectives: The brain-derived neurotrophic factor (BDNF) is a critical exercise-induced modulator of various neuroplasticity processes, including adult hippocampal neurogenesis. Environmental affordance for physical activity is a novel theory that aims to increase the BDNF through walking or climbing stairs, stimulated by the urban and interior environment. In a systematic review, this paper explores the association between walking, as a structured or free-living form of physical activity, and changes in the BDNF in humans with healthy locomotion. Method: A systematic review with a registered protocol, INPLASY2024110093, and following the PRISMA guidelines, includes English-language original research articles on adult and older adult human subjects who are locomotor-healthy, studies on walking as a structured exercise or free-living physical activity that is presented in a non-combined intervention, and must report changes in the BDNF as a dependent variable. The search was conducted using three databases: PubMed, Web of Science, and Scopus, resulting in 21 eligible studies. Results: This systematic review finds that the impact of walking on the BDNF is evidenced, but subject to moderate to high intensities in single bouts. At the same time, the long-term effects are yet to be fully understood, potentially due to the uptake of the BDNF for functional brain improvements, neuroplasticity processes, or muscle repair, instead of an accumulation of the BDNF itself, yet still confirm the important role of the BDNF for neurosustainability. Age and environmental factors such as heat are also found to affect the increase in the BDNF. The narrative synthesis provides elaborate explanations for understanding those complex dynamics before reaching future conclusions on the impact of walking or environmental affordance for physical activity on the changes in the BDNF concentrations. Conclusions: This systematic review highlights the potential role played by moderate- and high-intensity walking as a lifestyle intervention that can be utilised through the built environment to promote adaptive brain changes, through the sustainable regulation of the BDNF. Full article

Background: Degenerative spinal stenosis is a common condition associated with structural degeneration and pain, yet its molecular underpinnings remain incompletely understood. Growth-associated protein 43 (GAP-43), a key player in neuronal plasticity and regeneration, may serve as a biomarker for disease progression and pain severity. This study investigates the expression of GAP-43 at the mRNA and protein levels in the ligamentum flavum of affected patients. Methods: Samples were collected from 96 patients with degenerative spinal stenosis and 85 controls. GAP-43 mRNA expression was analyzed using reverse transcription–quantitative polymerase chain reaction (RT-qPCR), while protein levels were quantified via enzyme-linked immunosorbent assay (ELISA) and Western blot. Pain severity was assessed using the visual analog scale (VAS), and associations with lifestyle factors were analyzed. Results: GAP-43 mRNA expression was significantly downregulated in the study group compared to the controls (fold change = 0.58 ± 0.12, p < 0.05), with an inverse correlation to VAS pain severity (fold change = 0.76 at VAS 4 vs. 0.36 at VAS 10). Conversely, GAP-43 protein levels were markedly elevated in the study group (5.57 ± 0.21 ng/mL) when compared to controls (0.54 ± 0.87 ng/mL, p < 0.0001). Protein levels were also correlated with lifestyle factors, including smoking and alcohol consumption (p < 0.05). Conclusions: GAP-43 shows potential as a biomarker for pain severity and disease progression in degenerative spinal stenosis, in a manner influenced by lifestyle factors. Further research is needed to explore its diagnostic and therapeutic applications. 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

Parkinson’s disease (PD) neuropathology is marked by the selective loss of dopaminergic neurons in the substantia nigra pars compacta, accompanied by the widespread involvement of central and peripheral structures. Brain-derived neurotrophic factor (BDNF), a neurotrophin crucial for the survival of dopaminergic neurons, plays a pivotal role in neuronal and glial development, neuroprotection, and the modulation of synaptic plasticity. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive technique, enhances neurotransmitter release, trans-synaptic efficacy, signaling pathways, gene transcription, neuroplasticity, and neurotrophism. Evidence supports that high-frequency rTMS increases BDNF expression and improves task-specific cognitive deficits in PD patients. This article outlines a detailed protocol to investigate whether rTMS targeting the dorsolateral prefrontal cortex bilaterally induces changes in plasma BDNF levels, the plasma-derived exosomal BDNF concentration, and executive functions in individuals with PD. Identifying non-invasive interventions that effectively modulate the neurobiological mechanisms underlying cognitive and behavioral functions is critical for addressing cognitive impairments and mitigating disease progression in the PD population. This study aims to advance translational research by identifying biomarkers and developing therapeutic strategies for future applications in neurodegenerative diseases. Full article