scholarly journals Connection between Systemic Inflammation and Neuroinflammation Underlies Neuroprotective Mechanism of Several Phytochemicals in Neurodegenerative Diseases

2018 ◽  
Vol 2018 ◽  
pp. 1-16 ◽  
Author(s):  
Jintang Wang ◽  
Yuetao Song ◽  
Zheng Chen ◽  
Sean X. Leng
Keyword(s):  
Neurodegenerative Diseases ◽  
Systemic Inflammation ◽  
Neuronal Damage ◽  
Nutritional Intervention ◽  
Therapeutic Benefit ◽  
Brain Parenchyma ◽  
Health Concern ◽  
Gastrointestinal Function ◽  
Anti Inflammatory ◽  
The Brain

Oxidative damage, mitochondrial dysfunction, and neuroinflammation are strongly implicated in the pathogenesis of neurodegenerative diseases including Alzheimer’s disease (AD) and Parkinson’s disease (PD), and a substantial portion of elderly population at risk of these diseases requires nutritional intervention to benefit health due to lack of clinically relevant drugs. To this end, anti-inflammatory mechanisms of several phytochemicals such as curcumin, resveratrol, propolis, polyunsaturated fatty acids (PUFAs), and ginsenosides have been extensively studied. However, correlation of the phytochemicals with neuroinflammation or brain nutrition is not fully considered, especially in their therapeutic mechanism for neuronal damage or dysfunction. In this article, we review the advance in antioxidative and anti-inflammatory effects of phytochemicals and discuss the potential communication with brain microenvironment by improved gastrointestinal function, enhanced systemic immunity, and neuroprotective outcomes. These data show that phytochemicals may modulate and suppress neuroinflammation of the brain by several approaches: (1) reducing systemic inflammation and infiltration via the blood-brain barrier (BBB), (2) direct permeation into the brain parenchyma leading to neuroprotection, (3) enhancing integrity of disrupted BBB, and (4) vagal reflex-mediated nutrition and protection by gastrointestinal function signaling to the brain. Therefore, many phytochemicals have multiple potential neuroprotective approaches contributing to therapeutic benefit for pathogenesis of neurodegenerative diseases, and development of strategies for preventing these diseases represents a considerable public health concern and socioeconomic burden.

Peripheral Immunosenescence and Central Neuroinflammation: A Dangerous Liaison - A Dietary Approach

2020 ◽  
Vol 20 (9) ◽  
pp. 1391-1411 ◽  
Author(s):  
Thea Magrone ◽  
Manrico Magrone ◽  
Matteo A. Russo ◽  
Emilio Jirillo
Keyword(s):  
Neurodegenerative Diseases ◽  
T Regulatory Cells ◽  
Neuronal Damage ◽  
Age Related ◽  
The Central Nervous System ◽  
Anti Oxidant ◽  
Anti Inflammatory ◽  
Neuro Inflammation ◽  
Inflammatory Profile ◽  
The Brain

Background & Objectives: In old people, both innate and adaptive immune responses are impaired, thus leading to a condition of systemic inflamm-ageing, even including the involvement of the central nervous system (CNS). Aims: Here, main mechanisms of the immune ageing and neuro-inflammation will be discussed along with the dietary approaches for the modulation of age related diseases. Discussion: Neuroinflammation is caused by the passage of inflammatory mediators through the brain blood barrier to CNS. Then, in the brain, antigenic stimulation of microglia and/or its activation by peripheral cytokines lead to a robust production of free radicals with another wave of proinflammatory cytokines which, in turn, causes massive neuronal damage. Also, infiltrating T cells [T helper (h) and T cytotoxic cells] contribute to neuronal damage. Additionally, a peripheral imbalance between inflammatory Th17 cells and anti-inflammatory T regulatory cells seems to be prevalent in the aged brain, thus leading to a proinflammatory profile. Alzheimer’s disease, Parkinson’s disease and multiple sclerosis will be described as typical neurodegenerative diseases. Finally, modulation of the immune response thanks to the anti-oxidant and anti-inflammatory effects exerted by dietary products and nutraceuticals in ageing will be discussed. Special emphasis will be placed on polyunsaturated fatty acids, polyphenols, micronutrients and pre-probiotics and synbiotics. Conclusion: Ageing is characterized by an imbalance subversion of the immune system with a condition of inflamm-ageing. Neuroinflammation and neurodegenerative diseases seem to be a central manifestation of a peripheral perturbation of the immune machinery. Dietary products and nutraceuticals may lead to a down-regulation of the oxidative and pro-inflammatory profile in ageing.

scholarly journals Neuronal Damage and Neuroinflammation, a Bridge Between Bacterial Meningitis and Neurodegenerative Diseases

2021 ◽  
Vol 15 ◽  
Author(s):  
Kristine Farmen ◽  
Miguel Tofiño-Vian ◽  
Federico Iovino
Keyword(s):  
Bacterial Meningitis ◽  
Neurodegenerative Diseases ◽  
Neuronal Damage ◽  
Bacterial Pathogens ◽  
Neuronal Cell Death ◽  
Bacterial Pathogen ◽  
Neuronal Cell ◽  
Brain Parenchyma ◽  
Bacterial Interaction ◽  
The Brain

Bacterial meningitis is an inflammation of the meninges which covers and protects the brain and the spinal cord. Such inflammation is mostly caused by blood-borne bacteria that cross the blood-brain barrier (BBB) and finally invade the brain parenchyma. Pathogens such as Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae are the main etiological causes of bacterial meningitis. After trafficking across the BBB, bacterial pathogens in the brain interact with neurons, the fundamental units of Central Nervous System, and other types of glial cells. Although the specific molecular mechanism behind the interaction between such pathogens with neurons is still under investigation, it is clear that bacterial interaction with neurons and neuroinflammatory responses within the brain leads to neuronal cell death. Furthermore, clinical studies have shown indications of meningitis-caused dementia; and a variety of neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease and Huntington’s disease are characterized by the loss of neurons, which, unlike many other eukaryotic cells, once dead or damaged, they are seldom replaced. The aim of this review article is to provide an overview of the knowledge on how bacterial pathogens in the brain damage neurons through direct and indirect interactions, and how the neuronal damage caused by bacterial pathogen can, in the long-term, influence the onset of neurodegenerative disorders.

scholarly journals Neuroprotective Effect of Antioxidants in the Brain

2020 ◽  
Vol 21 (19) ◽  
pp. 7152 ◽  
Author(s):  
Kyung Hee Lee ◽  
Myeounghoon Cha ◽  
Bae Hwan Lee
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Diseases ◽  
Intracellular Signaling ◽  
Neuronal Damage ◽  
Neuroprotective Effect ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
High Energy ◽  
Antioxidant Compounds ◽  
The Brain

The brain is vulnerable to excessive oxidative insults because of its abundant lipid content, high energy requirements, and weak antioxidant capacity. Reactive oxygen species (ROS) increase susceptibility to neuronal damage and functional deficits, via oxidative changes in the brain in neurodegenerative diseases. Overabundance and abnormal levels of ROS and/or overload of metals are regulated by cellular defense mechanisms, intracellular signaling, and physiological functions of antioxidants in the brain. Single and/or complex antioxidant compounds targeting oxidative stress, redox metals, and neuronal cell death have been evaluated in multiple preclinical and clinical trials as a complementary therapeutic strategy for combating oxidative stress associated with neurodegenerative diseases. Herein, we present a general analysis and overview of various antioxidants and suggest potential courses of antioxidant treatments for the neuroprotection of the brain from oxidative injury. This review focuses on enzymatic and non-enzymatic antioxidant mechanisms in the brain and examines the relative advantages and methodological concerns when assessing antioxidant compounds for the treatment of neurodegenerative disorders.

scholarly journals Adenosine Triphosphate Accumulated Following Cerebral Ischemia Induces Neutrophil Extracellular Trap Formation

2020 ◽  
Vol 21 (20) ◽  
pp. 7668
Author(s):  
Seung-Woo Kim ◽  
Dashdulam Davaanyam ◽  
Song-I Seol ◽  
Hye-Kyung Lee ◽  
Hahnbie Lee ◽  
...  
Keyword(s):  
Adenosine Triphosphate ◽  
Neuronal Damage ◽  
Artery Occlusion ◽  
Brain Parenchyma ◽  
Neutrophil Extracellular Trap ◽  
Dependent Manner ◽  
Peptidylarginine Deiminase ◽  
Ischemic Brain ◽  
Cerebral Artery Occlusion ◽  
The Brain

In ischemic stroke, neutrophils infiltrate damaged brain tissue immediately following the ischemic insult and aggravate inflammation via various mechanisms which include neutrophil extracellular traps (NETs) formation. In the present study, we showed that adenosine triphosphate (ATP), a DAMP molecule, accumulates in the brain and induces NETosis in brain parenchyma and in circulating neutrophils (PMNs) isolated from a murine model of stroke induced by middle cerebral artery occlusion (MCAO). Expression of peptidylarginine deiminase-4 (PAD4), which induces citrullination of histones H3 (CitH3) and initiates NETosis, was significantly enhanced in brain parenchyma and blood PMNs following MCAO. ATP or BzATP (a prototypic P2X7R agonist) significantly enhanced the inductions of PAD4 and CitH3 in a P2X7R-dependent manner and intracellular Ca2+ influx, PKCα activation, and NADPH oxidase-dependent reactive oxygen species (ROS) production play critical roles in this ATP-P2X7R-mediated NETosis. In our MCAO animal model, NETosis was markedly suppressed by treatment with apyrase, an enzyme hydrolyzing ATP, but enhanced by co-treatment of BzATP, confirming ATP-P2X7R-mediated NETosis. Since ATP not only induced NETosis but was also extruded after NETosis, our results indicate that ATP accumulated in the ischemic brain induces NETosis, mediating a cross-talk linking NETosis with neuronal damage that might aggravate inflammation and brain damage.

scholarly journals Isomeric O-methyl cannabidiolquinones with dual BACH1/NRF2 activity

2020 ◽  
Author(s):  
Laura Casares ◽  
Juan Diego Unciti ◽  
Maria Eugenia Prados ◽  
Diego Caprioglio ◽  
Maureen Higgins ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Multiple Sclerosis ◽  
Neurodegenerative Diseases ◽  
Cell Models ◽  
Therapeutic Approaches ◽  
Neuroprotective Effects ◽  
Anti Oxidant ◽  
Anti Inflammatory ◽  
The Brain

ABSTRACTOxidative stress and inflammation in the brain are two key hallmarks of neurodegenerative diseases (NDs) such as Alzheimer’s, Parkinson’s, Huntington’s and multiple sclerosis. The axis NRF2-BACH1 has anti-inflammatory and anti-oxidant properties that could be exploited pharmacologically to obtain neuroprotective effects. Activation of NRF2 or inhibition of BACH1 are, individually, promising therapeutic approaches for NDs. Compounds with dual activity as NRF2 activators and BACH1 inhibitors, could therefore potentially provide a more robust antioxidant and anti-inflammatory effects, with an overall better neuroprotective outcome. The phytocannabinoid cannabidiol (CBD) inhibits BACH1 but lacks significant NRF2 activating properties. Based on this scaffold, we have developed a novel CBD derivative that is highly effective at both inhibiting BACH1 and activating NRF2. This new CBD derivative provides neuroprotection in cell models of relevance to Huntington’s disease, setting the basis for further developments in vivo.

scholarly journals The Ethanol Fraction of White Rose Petal Extract Abrogates Excitotoxicity-Induced Neuronal Damage In Vivo and In Vitro through Inhibition of Oxidative Stress and Proinflammation

Nutrients ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 1375 ◽  
Author(s):  
Jung-Min Yon ◽  
Yun-Bae Kim ◽  
Dongsun Park
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Neuronal Damage ◽  
Neuroprotective Effect ◽  
Radical Scavenging ◽  
Cresyl Violet ◽  
Anti Inflammatory ◽  
White Rose ◽  
The Brain

Since oxidative stress and inflammation are involved in seizure-related neurotoxicity, the neuroprotective effect of a white rose (Rosa hybrida) petal extract (WRPE) in mice that are challenged with kainic acid (KA) were examined using behavioral epileptiform seizures as well as biochemical and morphological parameters of oxidative stress and inflammation. WRPE (50–200 mg/kg) was orally administered to male ICR mice for 15 days, and intraperitoneally challenged with KA (30 mg/kg). Seizure activity, lipid peroxidation, inflammatory cytokines, and related enzymes were analyzed in the brain tissue, in addition to the morphological alterations in the hippocampal pyramidal neurons. Separately, antioxidant ingredients in WRPE were analyzed, and antioxidant, anti-inflammatory, and neuroprotective activities of WRPE were investigated in HB1.F3 human neural stem cells (NSCs) to elucidate underlying mechanisms. Total polyphenol and flavonoid contents in WRPE were 303.3 ± 15.3 mg gallic acid equivalent/g extract and 18.5 ± 2.2 mg catechin/g extract, respectively. WRPE exhibited strong radical-scavenging activities and inhibited lipid peroxidation in vitro, and protected glutamate-induced cytotoxicity in NSCs by suppressing inflammatory process. Treatment with WRPE attenuated epileptiform seizure scores to a half level in KA-challenged mice, and decreased hippocampal pyramidal neuronal injury and loss (cresyl violet and DAPI staining) as well as astrocyte activation (GFAP immunostaining). Lipid peroxidation was inhibited, and mRNA expression of antioxidant enzymes (GPx, PHGPx, SOD1, and SOD2) were recovered in the brain tissues. Inflammatory parameters (cytokines and enzymes) including NF-kB, IL-1β, TNF-α, IL-6, HMGB1, TGF-β, iNOS, COX2, and GFAP mRNAs and proteins were also down-regulated by WRPE treatment. Taken together, the results indicate that WRPE could attenuate KA-induced brain injury through antioxidative and anti-inflammatory activities.

scholarly journals Intranasal Delivery of Nerve Growth Factor in Neurodegenerative Diseases and Neurotrauma

2021 ◽  
Vol 12 ◽  
Author(s):  
Luigi Manni ◽  
Giorgio Conti ◽  
Antonio Chiaretti ◽  
Marzia Soligo
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Neurodegenerative Diseases ◽  
Brain Parenchyma ◽  
Delivery Methods ◽  
Nerve Growth ◽  
The Central Nervous System ◽  
Cholinergic Phenotype ◽  
Preclinical And Clinical Studies ◽  
The Brain

Since the 1980s, the development of a pharmacology based on nerve growth factor (NGF) has been postulated for the therapy of Alzheimer’s disease (AD). This hypothesis was based on the rescuing effect of the neurotrophin on the cholinergic phenotype of the basal forebrain neurons, primarily compromised during the development of AD. Subsequently, the use of NGF was put forward to treat a broader spectrum of neurological conditions affecting the central nervous system, such as Parkinson’s disease, degenerative retinopathies, severe brain traumas and neurodevelopmental dysfunctions. While supported by solid rational assumptions, the progress of a pharmacology founded on these hypotheses has been hampered by the difficulty of conveying NGF towards the brain parenchyma without resorting to invasive and risky delivery methods. At the end of the last century, it was shown that NGF administered intranasally to the olfactory epithelium was able to spread into the brain parenchyma. Notably, after such delivery, pharmacologically relevant concentration of exogenous NGF was found in brain areas located at considerable distances from the injection site along the rostral-caudal axis. These observations paved the way for preclinical characterization and clinical trials on the efficacy of intranasal NGF for the treatment of neurodegenerative diseases and of the consequences of brain trauma. In this review, a summary of the preclinical and clinical studies published to date will be attempted, as well as a discussion about the mechanisms underlying the efficacy and the possible development of the pharmacology based on intranasal conveyance of NGF to the brain.

Aging of Brain Related with Mitochondrial Dysfunctions

2020 ◽  
Vol 21 ◽  
Author(s):  
Vipin Dhote ◽  
Prem Samundre ◽  
Aditya Ganeshpurkar ◽  
Aman Upaganlawar
Keyword(s):  
Neurodegenerative Diseases ◽  
Psychiatric Symptoms ◽  
Neuronal Damage ◽  
The Elderly ◽  
Environmental Chemicals ◽  
Aging Brain ◽  
Mitochondrial Dysfunctions ◽  
Mitochondrial Functions ◽  
Key Issues ◽  
The Brain

Abstract:: Advancing age presents a major challenge for the elderly population in terms of quality of life. The risk of cognitive impairment, motor in-coordination, and behavioral inconsistency due to neuronal damage is relatively higher in aging individuals of society. The brain, through its structural and functional integrity, regulates vital physiological events; however, the susceptibility of the brain to aging-related disturbances signal the onset of neurodegenerative diseases. Mitochondrial dysfunctions impair bioenergetic mechanism, synaptic plasticity, and calcium homeostasis in the brain, thus sufficiently implying mitochondria as a prime causal factor in accelerating aging-related neurodegeneration. We reviewed the fundamental functions of mitochondria in a healthy brain and aimed to address the key issues in aging-related diseases by asking: 1) What goes wrong with mitochondria in the aging brain? 2) What are the implications of mitochondrial damage on motor functions and psychiatric symptoms? 3) How environmental chemicals and metabolic morbidities affect mitochondrial functions? Further, we share insight on opportunities and pitfalls in drug discovery approaches targeting mitochondria to slow down the progression of aging and related neurodegenerative diseases.

Changes in Coagulation following Brain Injury

2020 ◽  
Vol 46 (02) ◽  
pp. 155-166
Author(s):  
Marc Maegele ◽  
John Aversa ◽  
Mathew K. Marsee ◽  
Ross McCauley ◽  
Swetha Hanuma Chitta ◽  
...  
Keyword(s):  
Brain Injury ◽  
Point Of Care ◽  
Activated Protein C ◽  
Brain Parenchyma ◽  
Health Concern ◽  
Cerebral Vasculature ◽  
Clinical Presentations ◽  
Initial Injury ◽  
The Brain ◽  
Supporting Structures

AbstractTraumatic brain injury (TBI) is a worldwide public health concern due to increasing mortality, affecting around 10 million patients per year. A wide variety of clinical presentations are a function of the magnitude of injury and the anatomical perturbation of the brain parenchyma, supporting structures, and cerebral vasculature, with subsequent alteration of the blood–brain barrier. These disturbances correspond with the evolution of intracerebral hemorrhage and clinical outcomes. The associated hemostatic alterations associated with TBI are caused by the disruption of the delicate balance between bleeding and thrombosis formation, which can exacerbate initial injury. TBI-associated coagulopathy is a function of a cross-talk between coagulation and inflammation, with varying influences on the immunomodulation and regulation of coagulation that occur on platelets and the endothelium of injured TBI patients. In addition to the severity of initial injury, the following factors modulate the hemocoagulative response to TBI: time from the onset of injury to treatment, age, gender, catecholamine secretion, platelet dysfunction, endotheliopathy, premorbid anticoagulation, fibrinolysis, tissue factor, and activated protein C contribution. All these entities are intertwined and influence the pathologic evolution of TBI. These factors have implications for therapeutic options such as the choice of blood components for transfusion and hemostatic agents such as tranexamic acid. Monitoring hemostatic changes of TBI patients requires an understanding of these interactions between immunology and coagulation, which can be discerned by point-of-care viscoelastic testing with specific limitations. This review considers the implications of these interrelated influences on the evaluation of coagulopathy in TBI.

scholarly journals Treatment with Autophagy Inducer Trehalose Alleviates Memory and Behavioral Impairments and Neuroinflammatory Brain Processes in db/db Mice

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2557
Author(s):  
Tatiana A. Korolenko ◽  
Nina I. Dubrovina ◽  
Marina V. Ovsyukova ◽  
Nataliya P. Bgatova ◽  
Michael V. Tenditnik ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Genetic Model ◽  
Neuronal Damage ◽  
Blood Glucose Concentration ◽  
Immunohistochemical Analysis ◽  
Experimental Models ◽  
Fear Learning ◽  
Slight Reduction ◽  
Behavioral Disturbances ◽  
The Brain

Autophagy attenuation has been found in neurodegenerative diseases, aging, diabetes mellitus, and atherosclerosis. In experimental models of neurodegenerative diseases, the correction of autophagy in the brain reverses neuronal and behavioral deficits and hence seems to be a promising therapy for neuropathologies. Our aim was to study the effect of an autophagy inducer, trehalose, on brain autophagy and behavior in a genetic model of diabetes with signs of neuronal damage (db/db mice). A 2% trehalose solution was administered as drinking water during 24 days of the experiment. Expressions of markers of autophagy (LC3-II), neuroinflammation (IBA1), redox state (NOS), and neuronal density (NeuN) in the brain were assessed by immunohistochemical analysis. For behavioral phenotyping, the open field, elevated plus-maze, tail suspension, pre-pulse inhibition, and passive avoidance tests were used. Trehalose caused a slight reduction in increased blood glucose concentration, considerable autophagy activation, and a decrease in the neuroinflammatory response in the brain along with improvements of exploration, locomotor activity, anxiety, depressive-like behavior, and fear learning and memory in db/db mice. Trehalose exerted some beneficial peripheral and systemic effects and partially reversed behavioral alterations in db/db mice. Thus, trehalose as an inducer of mTOR-independent autophagy is effective at alleviating neuronal and behavioral disturbances accompanying experimental diabetes.

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