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Aging and Disease Mar 2024Although researched extensively the understanding regarding mechanisms underlying glaucoma pathogenesis remains limited. Further, the exact mechanism behind neuronal... (Review)
Review
Although researched extensively the understanding regarding mechanisms underlying glaucoma pathogenesis remains limited. Further, the exact mechanism behind neuronal death remains elusive. The role of neuroinflammation in retinal ganglion cell (RGC) death has been prominently theorised. This review provides a comprehensive summary of neuroinflammatory responses in glaucoma. A systematic search of Medline and Embase for articles published up to 8th March 2023 yielded 32 studies using post-mortem tissues from glaucoma patients. The raw data were extracted from tables and text to calculate the standardized mean differences (SMDs). These studies utilized post-mortem tissues from glaucoma patients, totalling 490 samples, compared with 380 control samples. Among the included studies, 27 reported glial cell activation based on changes to cellular morphology and molecular staining. Molecular changes were predominantly attributed to astrocytes (62.5%) and microglia (15.6%), with some involvement of Muller cells. These glial cell changes included amoeboid microglial cells with increased CD45 or HLA-DR intensity and hypertrophied astrocytes with increased glial fibrillary acidic protein labelling. Further, changes to extracellular matrix proteins like collagen, galectin, and tenascin-C suggested glial cells' influence on structural changes in the optic nerve head. The activation of DAMPs-driven immune response and the classical complement cascade was reported and found to be associated with activated glial cells in glaucomatous tissue. Increased pro-inflammatory markers such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were also linked to glial cells. Glial cell activation was also associated with mitochondrial, vascular, metabolic and antioxidant component disruptions. Association of the activated glial cells with pro-inflammatory responses, dysregulation of homeostatic components and antigen presentation indicates that glial cell responses influence glaucoma progression. However, the exact mechanism triggering these responses and underlying interactions remains unexplored. This necessitates further research using human samples for an increased understanding of the precise role of neuroinflammation in glaucoma progression.
PubMed: 38502591
DOI: 10.14336/AD.2024.0103 -
Croatian Medical Journal Apr 2019To propose potential mechanisms of action of electromagnetic fields (EMF) on astrocytes and microglia and to elucidate the role of heat shock proteins (HSP), adenosine...
AIM
To propose potential mechanisms of action of electromagnetic fields (EMF) on astrocytes and microglia and to elucidate the role of heat shock proteins (HSP), adenosine triphosphate (ATP), calcium ions (Ca2+), and hypoxia-inducible factor 1α (HIF1α) in neurorestoration following the application of EMF.
METHODS
We reviewed the existing studies within the public domain and cross-evaluated their results in order to conclude on the molecular mechanisms of microglia-astrocyte crosstalk at work during EMF treatment.
RESULTS
The existing studies suggest that EMF induces the increase of HSP70 expression and inhibition of HIF1α, thus decreasing inflammation and allowing the microglia-astrocyte crosstalk to initiate the formation of a glial scar within the central nervous system. Furthermore, by potentially up-regulating A2A and A3 adenosine receptors, EMF increases cAMP accumulation from astrocytes and reduces the expression of inflammatory cytokines TNF α and IL-8, thus initiating neurorestoration.
CONCLUSION
The microglia-astrocyte crosstalk during EMF treatment is crucial for the initiation of neurorestoration. Elucidating the exact mechanisms of EMF actions upon microglia and astrocytes, and its role in neurorestoration could be a key step in further research of the therapeutic potential of EMFs in various neurological disorders.
Topics: Adenosine Triphosphate; Animals; Astrocytes; Calcium; Cells, Cultured; Cytokines; Electromagnetic Fields; Heat-Shock Proteins; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Inflammation; Magnetic Field Therapy; Microglia; Neurodegenerative Diseases; Receptor Cross-Talk; Tumor Necrosis Factor-alpha
PubMed: 31044584
DOI: 10.3325/cmj.2019.60.127 -
Frontiers in Cellular Neuroscience 2024Schizophrenia is a complex and severe mental disorder that affects approximately 1% of the global population. It is characterized by a wide range of symptoms, including...
Schizophrenia is a complex and severe mental disorder that affects approximately 1% of the global population. It is characterized by a wide range of symptoms, including delusions, hallucinations, disorganized speech and behavior, and cognitive impairment. Recent research has suggested that the immune system dysregulation may play a significant role in the pathogenesis of schizophrenia, and glial cells, such as astroglia and microglia known to be involved in neuroinflammation and immune regulation, have emerged as potential players in this process. The aim of this systematic review is to summarize the glial hallmarks of schizophrenia, choosing as cellular candidate the astroglia and microglia, and focusing also on disease-associated psychological (cognitive and emotional) changes. We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched PubMed, Scopus, and Web of Science for articles that investigated the differences in astroglia and microglia in patients with schizophrenia, published in the last 5 years. The present systematic review indicates that changes in the density, morphology, and functioning of astroglia and microglia may be involved in the development of schizophrenia. The glial alterations may contribute to the pathogenesis of schizophrenia by dysregulating neurotransmission and immune responses, worsening cognitive capabilities. The complex interplay of astroglial and microglial activation, genetic/epigenetic variations, and cognitive assessments underscores the intricate relationship between biological mechanisms, symptomatology, and cognitive functioning in schizophrenia.
PubMed: 38419655
DOI: 10.3389/fncel.2024.1358450 -
Molecular Neurobiology Oct 2022Evidence from clinical, preclinical, and post-mortem studies supports the inflammatory/immune hypothesis of schizophrenia pathogenesis. Less evident is the link between... (Review)
Review
Linking Inflammation, Aberrant Glutamate-Dopamine Interaction, and Post-synaptic Changes: Translational Relevance for Schizophrenia and Antipsychotic Treatment: a Systematic Review.
Evidence from clinical, preclinical, and post-mortem studies supports the inflammatory/immune hypothesis of schizophrenia pathogenesis. Less evident is the link between the inflammatory background and two well-recognized functional and structural findings of schizophrenia pathophysiology: the dopamine-glutamate aberrant interaction and the alteration of dendritic spines architecture, both believed to be the "quantal" elements of cortical-subcortical dysfunctional network. In this systematic review, we tried to capture the major findings linking inflammation, aberrant glutamate-dopamine interaction, and post-synaptic changes under a direct and inverse translational perspective, a paramount picture that at present is lacking. The inflammatory effects on dopaminergic function appear to be bidirectional: the inflammation influences dopamine release, and dopamine acts as a regulator of discrete inflammatory processes involved in schizophrenia such as dysregulated interleukin and kynurenine pathways. Furthermore, the link between inflammation and glutamate is strongly supported by clinical studies aimed at exploring overactive microglia in schizophrenia patients and maternal immune activation models, indicating impaired glutamate regulation and reduced N-methyl-D-aspartate receptor (NMDAR) function. In addition, an inflammatory/immune-induced alteration of post-synaptic density scaffold proteins, crucial for downstream NMDAR signaling and synaptic efficacy, has been demonstrated. According to these findings, a significant increase in plasma inflammatory markers has been found in schizophrenia patients compared to healthy controls, associated with reduced cortical integrity and functional connectivity, relevant to the cognitive deficit of schizophrenia. Finally, the link between altered inflammatory/immune responses raises relevant questions regarding potential new therapeutic strategies specifically for those forms of schizophrenia that are resistant to canonical antipsychotics or unresponsive to clozapine.
Topics: Antipsychotic Agents; Dopamine; Glutamic Acid; Humans; Inflammation; Receptors, N-Methyl-D-Aspartate; Schizophrenia
PubMed: 35963926
DOI: 10.1007/s12035-022-02976-3 -
Phytomedicine : International Journal... Oct 2023Neurovascular glial unit (NVGU) dysfunction has been reported to be an early and critical event in the pathophysiology of Alzheimer's disease (AD) and vascular dementia...
BACKGROUND
Neurovascular glial unit (NVGU) dysfunction has been reported to be an early and critical event in the pathophysiology of Alzheimer's disease (AD) and vascular dementia (VD). Although herbal medicines, with their favorable safety profiles and low adverse effects, have been suggested to be useful for the treatment of cognitive impairment, the potential role of the NVGU as the target of the effects of herbal medicines is still unclear.
PURPOSE
This review aimed to retrieve evidence from experimental studies of phytopharmaceuticals targeting the NVGU for the treatment of cognitive impairment in AD and VD, and discussed the potential of phytopharmaceuticals to improve cognitive impairment from the perspective of the NVGU.
STUDY DESIGN AND METHODS
We systematically searched PubMed, Google Scholar, Web of Science, and CNKI. The keywords used for searching information on the NVGU in the treatment of cognitive impairments included "Alzheimer's disease," "Vascular dementia," "Herbal medicines," "Natural products," "Neurovascular," "Adverse reaction," and "Toxicity, etc." We selected studies on the basis of predefined eligibility criteria.
RESULTS
NVGU mainly consists of endothelial cells, pericytes, astrocytes, microglia, oligodendrocytes, and neurons, and damage to these cells can induce cognitive impairment by impairing the blood-brain barrier (BBB) and cerebral blood flow (CBF) as well as neuronal function. The active components of herbal medicines, including Ginkgo biloba L., Ginseng Radix et Rhizoma, Epimedium Folium, Chuanxiong Rhizoma, Carthami flos, and Acorus tatarinowii Schott, as well as traditional Chinese medicine prescriptions have shown the potential to improve BBB function and increase CBF to prevent cognitive impairment by inhibiting astrocyte and microglia activation, protecting oligodendrocyte myelin function, reducing neuronal apoptosis, and promoting angiogenesis.
CONCLUSIONS
Herbal medicines demonstrate great potential to prevent cognitive impairment. Multiple components from herbal medicines may function through different signaling pathways to target the NVGU. Future studies using novel drug-carrier or delivery systems targeting the NVGU will certainly facilitate the development of phytopharmaceuticals for AD and VD.
Topics: Alzheimer Disease; Cognitive Dysfunction; Dementia, Vascular; Drugs, Chinese Herbal; Endothelial Cells; Phytotherapy; Plant Extracts; Plants, Medicinal; Humans
PubMed: 37573807
DOI: 10.1016/j.phymed.2023.155009 -
Zeitschrift Fur Psychosomatische... Dec 2018Pain and fatigue - a systematic review Introduction: Chronic pain and fatigue are symptoms that often occur together and characterize the symptom picture of various...
UNLABELLED
Pain and fatigue - a systematic review Introduction: Chronic pain and fatigue are symptoms that often occur together and characterize the symptom picture of various diseases. Nevertheless, integrative explanatory approaches have so far received little attention in medical practice.
METHODS
Based on a systematic literature search in the Embase, Medline, PsychInfo, and CENTRAL databases, we searched for high-quality intervention studies for the simultaneous treatment of pain and fatigue.
RESULTS
From 1,496 total hits, 158 studies were included in the evaluation. The most commonly studied clinical pictures of the symptomcomplex were tumor catabolism, fibromyalgia, chronic fatigue, rheumatoid arthritis, and osteoarthritis.Current explanations of the symptom complex focus on the activation of proinflammatory microglia in centralized pain syndrome with multiple effects on neurotransmission, neuroendocrinology, neuroplasticity, and the autonomic nervous system. In this model, fatigue can be understood as an evolutionary, meaningful symptom protective of the organism.
CONCLUSIONS
A deeper understanding of the relationship between centralized pain syndrome and fatigue allows for new explanatory and treatment approaches.
Topics: Chronic Pain; Fatigue; Fibromyalgia; Humans
PubMed: 30829171
DOI: 10.13109/zptm.2018.64.4.365 -
Neuroscience and Biobehavioral Reviews Aug 2019Bipolar disorder (BD) is a complex neurobiological disease. It is likely that both neurons and glial cells are affected in BD, yet how these cell types are changed at... (Review)
Review
Bipolar disorder (BD) is a complex neurobiological disease. It is likely that both neurons and glial cells are affected in BD, yet how these cell types are changed at the structural and functional level is still largely unknown. In this review we provide an overview of postmortem studies analyzing structural cellular changes in BD, including the density, number and size of neurons and glia. We categorize the results per cell-type and validate outcome measures per brain region. Despite variations by brain region, outcome measure and methodology, several patterns could be identified. Total neuron, total glia, and cell subtypes astrocyte, microglia and oligodendrocyte presence appears unchanged in the BD brain. Interneuron density may be decreased across various cortical areas, yet findings of interneuron subpopulations show discrepancies. This structural review brings to light issues in validation and replication. Future research should therefore prioritize the validation of existing studies in order to increasingly refine the conceptual models of BD.
Topics: Bipolar Disorder; Brain; Humans; Neuroglia; Neurons
PubMed: 31163205
DOI: 10.1016/j.neubiorev.2019.05.027 -
Journal of Ethnopharmacology May 2024Traditional plant-based medicines (TMs) have been widely used to prevent chronic oxaliplatin-induced peripheral neurotoxicity (OIPN). However, the prevention and safety... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of traditional plant-based medicines for preventing chronic oxaliplatin-induced peripheral neurotoxicity in patients with colorectal cancer: A systematic review and meta-analysis with core herb contribution.
ETHNOPHARMACOLOGICAL RELEVANCE
Traditional plant-based medicines (TMs) have been widely used to prevent chronic oxaliplatin-induced peripheral neurotoxicity (OIPN). However, the prevention and safety of TMs for chronic OIPN remain ambiguous. Furthermore, diverse TM prescriptions and complicated components limit in-depth research on the mechanisms of TMs.
AIM OF THIS STUDY
To determine core TMs and potential pharmacological pathways on the basis of a thorough investigation into the preventive benefits and safety of oral TMs for chronic OIPN in colorectal cancer (CRC).
METHODS
A search of the PubMed, Cochrane, Embase, CNKI, VIP, and Wanfang databases for RCTs reporting on TMs for chronic OIPN was conducted through December 1, 2022. Subgroup analysis, sensitivity analysis and meta-regression were applied to assess the impacts of influencing variables. The assessment of Risk of Bias was relied on Cochrane Risk of Bias tool. The funnel plot, Egger's test, and the Trim and Fill method were applied to identify potential publication bias. Trial sequential analyses (TSA) were carried out by the TSA tool to increase the robustness. The assessment of the quality of evidence was according to the GRADE system. System pharmacology analysis was employed to screen core herbal combinations to elucidate possible mechanisms for preventing chronic OIPN in CRC.
RESULTS
The pooled effect estimate with robustness increased by TSA analysis demonstrated that oral TMs appeared to significantly decrease the incidence of chronic OIPN (RR = 0.66, 95% CI (0.56, 0.78); P<0.00001), leukocytopenia (RR = 0.65, 95% CI (0.54,0.79); P<0.00001), and nausea and vomiting (RR = 0.72, 95% CI (0.61,0.84); P<0.0001) as well as improve the Objective Response Rate (ORR) (RR = 1.31, 95% CI (1.09,1.56); P = 0.003). The incidence of severe chronic OIPN was revealed a significant reduction, particularly when chemotherapy was administered for periods of time shorter than six months (RR = 0.33, 95% CI (0.15,0.71); P = 0.005; actuation duration<3 months; RR = 0.33, 95% CI (0.17,0.62); P = 0.0007; actuation duration≥3 months, <6 months). The considerable heterogeneity among studies may be attributable to the severity of dysfunction categorized by grade and accumulated dosage. Using core TMs consisting of Astragalus membranaceus (Fisch.) Bunge, Atractylodes Macrocephala Koidz., Poria cocos (Schw.) Wolf, and Codonopsis pilosula (Franch.) Nannf. To regulate nuclear factor-kappa B against inflammation caused by activation of microglia might be an approach to preventing chronic OIPN.
CONCLUSIONS
TMs appear to be effective and safe in the prevention of chronic OIPN, especially severe chronic OIPN. Additionally, core TMs consisting of Astragalus membranaceus (Fisch.) Bunge, Atractylodes Macrocephala Koidz., Poria cocos (Schw.) Wolf, and Codonopsis pilosula (Franch.) Nannf were presumably responsible for reducing the incidence of chronic OIPN, and the mechanism may be related to relieving inflammation. However, quality-assured trials with long-term follow-up for exploring inflammatory factors and preliminary research on core TMs and pharmacological pathways are needed.
Topics: Animals; Humans; Oxaliplatin; Wolves; Neurotoxicity Syndromes; Colorectal Neoplasms; Inflammation
PubMed: 38211824
DOI: 10.1016/j.jep.2024.117735 -
ACS Chemical Neuroscience Nov 2020Neuroinflammation is indicated in the pathogenesis of several acute and chronic neurological disorders. Acute lesions in the brain parenchyma induce intense and highly...
Neuroinflammation is indicated in the pathogenesis of several acute and chronic neurological disorders. Acute lesions in the brain parenchyma induce intense and highly complex neuroinflammatory reactions with similar mechanisms among various disease prototypes. Microglial cells in the CNS sense tissue damage and initiate inflammatory responses. The cellular and humoral constituents of the neuroinflammatory reaction to brain injury contribute significantly to secondary brain damage and neurodegeneration. Inflammatory cascades such as proinflammatory cytokines from invading leukocytes and direct cell-mediated cytotoxicity between lymphocytes and neurons are known to cause "collateral damage" in models of acute brain injury. In addition to degeneration and neuronal cell loss, there are secondary inflammatory mechanisms that modulate neuronal activity and affect neuroinflammation which can even be detected at the behavioral level. Hence, several of health conditions result from these pathogenetic conditions which are underlined by progressive neuronal function loss due to chronic inflammation and oxidative stress. In the first part of this Review, we discuss critical neuroinflammatory mediators and their pathways in detail. In the second part, we review the phytochemicals which are considered as potential therapeutic molecules for treating neurodegenerative diseases with an inflammatory component.
Topics: Brain; Humans; Inflammation; Microglia; Neurodegenerative Diseases; Neurons
PubMed: 33146995
DOI: 10.1021/acschemneuro.0c00427 -
Biomedicines Dec 2022Lafora disease (LD) is a neurodegenerative condition characterized by the accumulation of polyglucosan bodies (PBs) throughout the brain. Alongside metabolic and... (Review)
Review
BACKGROUND
Lafora disease (LD) is a neurodegenerative condition characterized by the accumulation of polyglucosan bodies (PBs) throughout the brain. Alongside metabolic and molecular alterations, neuroinflammation has emerged as another key histopathological feature of LD.
METHODS
To investigate the role of astrocytes and microglia in LD, we performed a systematic review according to the PRISMA statement. PubMed, Scopus, and Web-of-Science database searches were performed independently by two reviewers.
RESULTS
Thirty-five studies analyzing the relationship of astrocytes and microglia with LD and/or the effects of anti-inflammatory treatments in LD animal models were identified and included in the review. Although LD has long been dominated by a neuronocentric view, a growing body of evidence suggests a role of glial cells in the disease, starting with the finding that these cells accumulate PBs. We discuss the potential meaning of glial PB accumulations, the likely factors activating glial cells, and the possible contribution of glial cells to LD neurodegeneration and epilepsy.
CONCLUSIONS
Given the evidence for the role of neuroinflammation in LD, future studies should consider glial cells as a potential therapeutic target for modifying/delaying LD progression; however, it should be kept in mind that these cells can potentially assume multiple reactive phenotypes, which could influence the therapeutic response.
PubMed: 36551859
DOI: 10.3390/biomedicines10123103