Oxidative/Nitrosative Stress and Brain Involvement in Sepsis: A Relationship Supported by Immunohistochemistry DOI Creative Commons
Giuseppe Bertozzi, Michela Ferrara, Mariagrazia Calvano

et al.

Medicina, Journal Year: 2024, Volume and Issue: 60(12), P. 1949 - 1949

Published: Nov. 26, 2024

Background and Objectives: A large amount of recent evidence suggests that cellular inability to consume oxygen could play a notable part in promoting sepsis as consequence mitochondrial dysfunction oxidative stress. The latter could, fact, represent fundamental stage the evolution “natural history” sepsis. Following study previously conducted by same working group on heart samples, present research project aims evaluate, through an immunohistochemical study, existence and/or extent stress brains subjects who died due define, after reviewing literature, its contribution septic process support use medications aimed at correcting redox anomalies management patients. Materials Methods: 10 cases healthcare facilities with ante-mortem clinical-laboratory signs allowed diagnosis shock were selected case studies, 1 subject immediately following road traffic accident was used negative control. Samples cerebral cortex then taken, fixed formalin, subjected sections which performed using anti-NOX-2, NT, iNOS, 8-OHdG antibodies. Results: results emerging from demonstrate despite variable expressivity for NOX2 markers, brain samples demonstrated univocal high positivity marker. Conclusions: This would allow us hypothesize how, regardless mechanism production ROS NOS (iNOS or mediated) pathophysiological mechanisms are triggered during sepsis, damage DNA represents event this whole leads and, is directly correlated sepsis-dependent mortality. Neurons, conversely, appear be more sensitive because low number protective scavenger molecules (catalase, glutathione peroxidase, GSH, vitamin E). Therefore, reduced production, manifestation remains high. evidence, together previous can only introduction substances antioxidant function guidelines treatment

Language: Английский

Advancing neurological disorders therapies: Organic nanoparticles as a key to blood-brain barrier penetration DOI Creative Commons
Zahra Razavi,

Seyed Sina Alizadeh,

F. S. Razavi

et al.

International Journal of Pharmaceutics, Journal Year: 2025, Volume and Issue: 670, P. 125186 - 125186

Published: Jan. 8, 2025

The blood-brain barrier (BBB) plays a vital role in protecting the central nervous system (CNS) by preventing entry of harmful pathogens from bloodstream. However, this also presents significant obstacle when it comes to delivering drugs for treatment neurodegenerative diseases and brain cancer. Recent breakthroughs nanotechnology have paved way creation wide range nanoparticles (NPs) that can serve as carriers diagnosis therapy. Regarding their promising properties, organic NPs potential be used effective drug delivery across BBB based on recent advancements. These remarkable ability penetrate using various mechanisms. This review offers comprehensive examination intricate structure distinct properties BBB, emphasizing its crucial function preserving balance regulating transport ions molecules. disruption conditions such stroke, Alzheimer's disease, Parkinson's disease highlights importance developing creative approaches drugs. Through encapsulation therapeutic molecules precise targeting processes vasculature, NP formulations present hopeful strategy improve BBB. We explore changes pathological investigate factors affect successful into brain. In addition, we most systems associated with shown positive results treating ischemic disorders. opens up new possibilities nanotechnology-based therapies cerebral diseases.

Language: Английский

Citations

12
Glial Perturbation in Metal Neurotoxicity: Implications for Brain Disorders DOI Creative Commons
Olayemi K. Ijomone, Ukwubile Ileje Inelo, Vivian O. Aneke

et al.

Neuroglia, Journal Year: 2025, Volume and Issue: 6(1), P. 4 - 4

Published: Jan. 6, 2025

Overexposure of humans to heavy metals and essential poses a significant risk for the development neurological neurodevelopmental disorders. The mechanisms through which these exert their effects include generation reactive oxygen species, mitochondrial dysfunction, activation inflammatory pathways, disruption cellular signaling. function glial cells in brain maintenance homeostasis cannot be overlooked. are particularly susceptible metal-induced neurotoxicity. Accumulation promotes microglial activation, triggering responses that can coincide with other neurotoxicity, inducing alteration synaptic transmission, cognitive deficit, neuronal damage. In this review, we highlighted role dysfunction some selected neurodegenerative diseases We further dive into how exposure such as nickel, manganese, methyl mercury, cadmium, iron, arsenic, lead affect functions microglia, astrocytes, oligodendrocytes they on relation Potential therapeutic interventions use new improved chelating agents antioxidant therapies might approach alleviating perturbations.

Language: Английский

Citations

3
The Mechanisms of Sepsis Induced Coagulation Dysfunction and Its Treatment DOI Creative Commons
Lei Zhu, He Dong, Linfeng Li

et al.

Journal of Inflammation Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 1479 - 1495

Published: Feb. 1, 2025

Sepsis is a critical condition characterized by organ dysfunction due to dysregulated response infection that poses significant global health challenges. Coagulation nearly ubiquitous among sepsis patients. Its mechanisms involve platelet activation, coagulation cascade inflammatory reaction imbalances, immune dysregulation, mitochondrial damage, neuroendocrine network disruptions, and endoplasmic reticulum (ER) stress. These factors not only interact but also exacerbate one another, leading severe dysfunction. This review illustrates the of sepsis-induced coagulopathy, with focus on tissue factor endothelial glycocalyx release neutrophil extracellular traps (NETs), all which are potential targets for therapeutic interventions.

Language: Английский

Citations

3
"Lipopolysaccharide-induced animal models for neuroinflammation – An overview." DOI Creative Commons
Ana Silva, Mariana Bernardo Fiadeiro, Liliana Bernardino

et al.

Journal of Neuroimmunology, Journal Year: 2023, Volume and Issue: 387, P. 578273 - 578273

Published: Dec. 31, 2023

Neuroinflammation is a pathological mechanism contributing to neurodegenerative diseases. For in-depth studies of neuroinflammation, several animal models reported reproducing behavioral dysfunctions and cellular mechanisms induced by brain inflammation. One the most popular neuroinflammation one generated lipopolysaccharide exposure. Despite its importance, results using this model show high heterogeneity, making it difficult analyze compare outcomes between studies. Therefore, current review aims summarize different experimental paradigms used reproduce exposure respective outcomes, helping choose that better suits each specific research aim.

Language: Английский

Citations

23
IL-8 (CXCL8) Correlations with Psychoneuroimmunological Processes and Neuropsychiatric Conditions DOI Open Access

Anton Shkundin,

Angelos Halaris

Journal of Personalized Medicine, Journal Year: 2024, Volume and Issue: 14(5), P. 488 - 488

Published: May 3, 2024

Interleukin-8 (IL-8/CXCL8), an essential CXC chemokine, significantly influences psychoneuroimmunological processes and affects neurological psychiatric health. It exerts a profound effect on immune cell activation brain function, suggesting potential roles in both neuroprotection neuroinflammation. IL-8 production is stimulated by several factors, including reactive oxygen species (ROS) known to promote inflammation disease progression. Additionally, CXCL8 gene polymorphisms can alter production, leading differences susceptibility, progression, severity across populations. levels vary among neuropsychiatric conditions, demonstrating sensitivity psychosocial stressors severity. be detected blood circulation, cerebrospinal fluid (CSF), urine, making it promising candidate for broad-spectrum biomarker. This review highlights the need further research diverse effects of associated implications personalized medicine. A thorough understanding its complex role could lead development more effective treatment strategies conditions.

Language: Английский

Citations

7
Omega-3 Fatty Acids and Neuroinflammation in Depression: Targeting Damage-Associated Molecular Patterns and Neural Biomarkers DOI Creative Commons
Ikbal Andrian Malau, Jane Pei‐Chen Chang,

Yi‐Wen Lin

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(21), P. 1791 - 1791

Published: Oct. 29, 2024

Major Depressive Disorder (MDD) is a prevalent mental health condition with complex pathophysiology involving neuroinflammation, neurodegeneration, and disruptions in neuronal glial cell function. Microglia, the innate immune cells of central nervous system, release inflammatory cytokines response to pathological changes associated MDD. Damage-associated molecular patterns (DAMPs) act as alarms, triggering microglial activation subsequent cytokine release. This review examines cellular mechanisms underlying MDD pathophysiology, focusing on lipid-mediated modulation neuroinflammation. We explore intricate roles microglia astrocytes propagating cascades discuss how these processes affect integrity at level. Central our analysis are three key molecules: High Mobility Group Box 1 (HMGB1) S100 Calcium Binding Protein β (S100β) alarmins, Neuron-Specific Enolase (NSE) an indicator stress. present evidence from vitro ex vivo studies demonstrating molecules reflect contribute neuroinflammatory milieu characteristic The then explores potential omega-3 polyunsaturated fatty acids (ω-3 PUFAs) neuroinflammation modulators, examining their effects activation, production, resilience models depression. critically analyze experimental data ω-3 PUFA supplementation influences expression HMGB1, S100β, NSE cultures. By integrating findings lipidomic neurobiology, this aims elucidate by which PUFAs may exert antidepressant through markers. These insights understanding neuroprotection inform development targeted, lipid-based therapies for both depression neurodegenerative disorders.

Language: Английский

Citations

7
Morphological diversity of microglia: implications for learning, environmental adaptation, ageing, sex differences and neuropathology DOI
Marcus Augusto‐Oliveira, Gabriela de Paula Arrifano,

Caio Gustavo Leal-Nazaré

et al.

Neuroscience & Biobehavioral Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 106091 - 106091

Published: March 1, 2025

Language: Английский

Citations

1
Human dental pulp stem cells mitigate the neuropathology and cognitive decline via AKT-GSK3β-Nrf2 pathways in Alzheimer’s disease DOI Creative Commons
Wei Xiong, Ye Liu,

Heng Zhou

et al.

International Journal of Oral Science, Journal Year: 2024, Volume and Issue: 16(1)

Published: May 13, 2024

Abstract Oxidative stress is increasingly recognized as a major contributor to the pathophysiology of Alzheimer’s disease (AD), particularly in early stages disease. The multiplicity advantages stem cell transplantation make it fascinating therapeutic strategy for many neurodegenerative diseases. We herein demonstrated that human dental pulp cells (hDPSCs) mediated oxidative improvement and neuroreparative effects vitro AD models, playing critical roles regulating polarization hyperreactive microglia recovery damaged neurons. Importantly, these were reflected 10-month-old 3xTg-AD mice after single hDPSCs, with treated showing significant cognitive function neuropathological features. Mechanistically, antioxidant neuroprotective effects, well enhancements elicited by at least partially Nrf2 nuclear accumulation downstream enzymes expression through activation AKT-GSK3β-Nrf2 signaling pathway. In conclusion, our findings corroborated capacity hDPSCs reshape microenvironment both vivo which may be tremendous potential candidate

Language: Английский

Citations

5
Intersecting Pathways: The Role of Metabolic Dysregulation, Gastrointestinal Microbiome, and Inflammation in Acute Ischemic Stroke Pathogenesis and Outcomes DOI Open Access
Jarosław Nuszkiewicz,

Beata Kukulska-Pawluczuk,

Katarzyna Piec

et al.

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(14), P. 4258 - 4258

Published: July 21, 2024

Acute ischemic stroke (AIS) remains a major cause of mortality and long-term disability worldwide, driven by complex multifaceted etiological factors. Metabolic dysregulation, gastrointestinal microbiome alterations, systemic inflammation are emerging as significant contributors to AIS pathogenesis. This review addresses the critical need understand how these factors interact influence risk outcomes. We aim elucidate roles dysregulated adipokines in obesity, impact gut microbiota disruptions, neuroinflammatory cascade initiated lipopolysaccharides (LPS) AIS. Dysregulated obesity exacerbate inflammatory responses, increasing severity. Disruptions subsequent LPS-induced neuroinflammation further link Advances neuroimaging biomarker development have improved diagnostic precision. Here, we highlight for approach management, integrating metabolic, microbiota, insights. Potential therapeutic strategies targeting pathways could significantly improve prevention treatment. Future research should focus on elucidating developing targeted interventions mitigate impacts metabolic imbalances,

Language: Английский

Citations

4
HIV-associated neurocognitive disorder: key implications of the microbiota-gut-brain axis DOI Creative Commons

Aizhen Hu,

Silvère D. Zaongo, Vijay Harypursat

et al.

Frontiers in Microbiology, Journal Year: 2024, Volume and Issue: 15

Published: Aug. 2, 2024

HIV-associated neurocognitive disorder (HAND) is now recognized to be relatively common in people living with HIV (PLWH), and remains a cause of cognitive impairment. Unfortunately, the fundamental pathogenic processes underlying this specific outcome infection have not as yet been fully elucidated. With increased interest research related microbiota-gut-brain axis, gut-brain axis has shown play critical roles regulating central nervous system disorders such Alzheimer's disease Parkinson's disease. PLWH are characterized by particular affliction, referred gut-associated dysbiosis syndrome, which provokes an alteration microbial composition diversity, their associated metabolite within gut. Interestingly, gut microbiota also key element, both positively negatively influences human brain health, including functioning development (CNS). In review, based on published evidence, we critically discuss relevant interactions between pathogenesis HAND context infection. It likely that manifestation mainly results from (i) syndrome leaky one hand (ii) inflammation other hand. words, preceding features alter (microbes metabolites) promote proinflammatory immune responses singularly or tandem damage neurons and/or induce inadequate neuronal signaling. Thus, fairly prevalent PLWH. This work aims demonstrate quest prevent possibly treat HAND, may ultimately represent therapeutically targetable "host factor."

Language: Английский

Citations

4