scholarly journals Palmitoylethanolamide Modulation of Microglia Activation: Characterization of Mechanisms of Action and Implication for Its Neuroprotective Effects

2021 ◽  
Vol 22 (6) ◽  
pp. 3054
Author(s):  
Alessia D’Aloia ◽  
Laura Molteni ◽  
Francesca Gullo ◽  
Elena Bresciani ◽  
Valentina Artusa ◽  
...  
Keyword(s):  
Inflammatory Markers ◽  
Neuronal Damage ◽  
Electrode Array ◽  
Microglial Cells ◽  
Toll Like Receptor 4 ◽  
Neuroprotective Effects ◽  
M1 Polarization ◽  
Anti Inflammatory

Palmitoylethanolamide (PEA) is an endogenous lipid produced on demand by neurons and glial cells that displays neuroprotective properties. It is well known that inflammation and neuronal damage are strictly related processes and that microglia play a pivotal role in their regulation. The aim of the present work was to assess whether PEA could exert its neuroprotective and anti-inflammatory effects through the modulation of microglia reactive phenotypes. In N9 microglial cells, the pre-incubation with PEA blunted the increase of M1 pro-inflammatory markers induced by lipopolysaccharide (LPS), concomitantly increasing those M2 anti-inflammatory markers. Images of microglial cells were processed to obtain a set of morphological parameters that highlighted the ability of PEA to inhibit the LPS-induced M1 polarization and suggested that PEA might induce the anti-inflammatory M2a phenotype. Functionally, PEA prevented Ca2+ transients in both N9 cells and primary microglia and antagonized the neuronal hyperexcitability induced by LPS, as revealed by multi-electrode array (MEA) measurements on primary cortical cultures of neurons, microglia, and astrocyte. Finally, the investigation of the molecular pathway indicated that PEA effects are not mediated by toll-like receptor 4 (TLR4); on the contrary, a partial involvement of cannabinoid type 2 receptor (CB2R) was shown by using a selective receptor inverse agonist.

Neuroprotection via AT2 receptor agonists in ischemic stroke

2018 ◽  
Vol 132 (10) ◽  
pp. 1055-1067 ◽  
Author(s):  
Douglas M. Bennion ◽  
U. Muscha Steckelings ◽  
Colin Sumners
Keyword(s):  
Ischemic Stroke ◽  
Neuronal Damage ◽  
Recombinant Tissue Plasminogen Activator ◽  
Neurological Deficits ◽  
At2 Receptor ◽  
Neuroprotective Effects ◽  
Receptor Agonists ◽  
Stroke Epidemiology ◽  
The Brain

Stroke is a devastating disease that afflicts millions of people each year worldwide. Ischemic stroke, which accounts for ~88% of cases, occurs when blood supply to the brain is decreased, often because of thromboembolism or atherosclerotic occlusion. This deprives the brain of oxygen and nutrients, causing immediate, irreversible necrosis within the core of the ischemic area, but more delayed and potentially reversible neuronal damage in the surrounding brain tissue, the penumbra. The only currently approved therapies for ischemic stroke, the thrombolytic agent recombinant tissue plasminogen activator (rtPA) and the endovascular clot retrieval/destruction processes, are aimed at restoring blood flow to the infarcted area, but are only available for a minority of patients and are not able in most cases to completely restore neurological deficits. Consequently, there remains a need for agents that will protect neurones against death following ischemic stroke. Here, we evaluate angiotensin II (Ang II) type 2 (AT2) receptor agonists as a possible therapeutic target for this disease. We first provide an overview of stroke epidemiology, pathophysiology, and currently approved therapies. We next review the large amount of preclinical evidence, accumulated over the past decade and a half, which indicates that AT2 receptor agonists exert significant neuroprotective effects in various animal models, and discuss the potential mechanisms involved. Finally, after discussing the challenges of delivering blood–brain barrier (BBB) impermeable AT2 receptor agonists to the infarcted areas of the brain, we summarize the evidence for and against the development of these agents as a promising therapeutic strategy for ischemic stroke.

scholarly journals Inverse Agonism of Cannabinoid Receptor Type 2 Confers Anti-inflammatory and Neuroprotective Effects Following Status Epileptics

2020 ◽  
Vol 57 (6) ◽  
pp. 2830-2845 ◽  
Author(s):  
Ying Yu ◽  
Lexiao Li ◽  
Davis T. Nguyen ◽  
Suni M. Mustafa ◽  
Bob M. Moore ◽  
...  
Keyword(s):  
Cannabinoid Receptor ◽  
Receptor Type ◽  
Neuroprotective Effects ◽  
Inverse Agonism ◽  
Cannabinoid Receptor Type 2 ◽  
Anti Inflammatory

Detailed characterization of the endocannabinoid system in human macrophages and foam cells, and anti-inflammatory role of type-2 cannabinoid receptor

2014 ◽  
Vol 233 (1) ◽  
pp. 55-63 ◽  
Author(s):  
Valerio Chiurchiù ◽  
Mirko Lanuti ◽  
Giuseppina Catanzaro ◽  
Filomena Fezza ◽  
Cinzia Rapino ◽  
...  
Keyword(s):  
Cannabinoid Receptor ◽  
Endocannabinoid System ◽  
Foam Cells ◽  
Detailed Characterization ◽  
Human Macrophages ◽  
Anti Inflammatory

Lifestyle Measures to Reduce Inflammation

2011 ◽  
Vol 6 (1) ◽  
pp. 4-13 ◽  
Author(s):  
Glenn A. Gaesser ◽  
Siddhartha S. Angadi ◽  
Dana M. Ryan ◽  
Carol S. Johnston
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Aerobic Exercise ◽  
Inflammatory Markers ◽  
Dietary Factors ◽  
Low Grade ◽  
Inflammatory Status ◽  
Anti Inflammatory ◽  
Low Grade Inflammation

Chronic low-grade inflammation associated with cardiovascular disease and type 2 diabetes (T2D) may be ameliorated with exercise and/or diet. High levels of physical activity and/or cardiorespiratory fitness are associated with reduced risk of low-grade inflammation. Both aerobic and resistance exercise have been found to improve inflammatory status, with the majority of evidence suggesting that aerobic exercise may have broader anti-inflammatory effects. In particular, aerobic exercise appears to improve the balance between pro- and anti-inflammatory markers. Improvement in inflammatory status is most likely to occur in persons with elevated levels of pro-inflammatory markers prior to intervention. A number of dietary factors, including fiber-rich foods, whole grains, fruits (especially berries), omega-3 fatty acids, antioxidant vitamins (eg, C and E), and certain trace minerals (eg, zinc) have been documented to reduce blood concentrations of inflammatory markers. Anti-inflammatory foods may also help mitigate the pro-inflammatory postprandial state that is particularly evident after ingestion of meals high in saturated fat. Intensive lifestyle interventions involving both exercise and diet appear to be most effective. For the most part, anti-inflammatory effects of exercise and diet are independent of weight loss. Thus overweight and obese men and women, who are most likely to have a pro-inflammatory profile, do not necessarily have to normalize body mass index to improve inflammatory status and reduce risk of type 2 diabetes and cardiovascular disease.

scholarly journals Some mechanisms of inflammation development in type 2 diabetes mellitus

2021 ◽  
Vol 24 (4) ◽  
pp. 334-341
Author(s):  
L. A. Bochkareva ◽  
L. V. Nedosugova ◽  
N. A. Petunina ◽  
M. Е. Теlnova ◽  
E. V. Goncharova
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Intracellular Signaling ◽  
Peripheral Tissues ◽  
Surface Receptors ◽  
Peripheral Insulin Resistance ◽  
Systemic Insulin Resistance ◽  
M1 Polarization ◽  
Anti Inflammatory

Inflammation plays a key role in the development and progression of type 2 diabetes (T2DM), a disease characterized by peripheral insulin resistance and systemic glucolipotoxicity. The main source of inflammation in the early stages of the disease is visceral adipose tissue (VT). Macrophages are innate immune cells that are present in all peripheral tissues, including VT. Violation of the response of VT (MT) macrophages to changes in the microenvironment underlies aberrant inflammation and the development of local and systemic insulin resistance. The inflammatory activation of macrophages is regulated at several levels: stimulation of cell surface receptors, intracellular signaling, transcription, and metabolic levels. Which are activated by the transformation of macrophages along the pro-inflammatory or anti-inflammatory pathways. Such polarization of macrophages in modern immunology is divided into classical anti-inflammatory M1 polarization and alternative anti-inflammatory M2 polarization of macrophages. The M1 / M2 ratio of macrophages in the process of inflammation ensures the resolution of inflammation at different stages of its development. The review considers the main mechanisms involved in VT inflammation and the development of insulin resistance in T2DM, supported with the participation of immunocompetent cells, M1 / M2, as well as growth factors and humoral immunity factors secreted during this process.

scholarly journals trans-Cinnamaldehyde Inhibits Microglial Activation and Improves Neuronal Survival against Neuroinflammation in BV2 Microglial Cells with Lipopolysaccharide Stimulation

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Yan Fu ◽  
Pin Yang ◽  
Yang Zhao ◽  
Liqing Zhang ◽  
Zhangang Zhang ◽  
...  
Keyword(s):  
Neurodegenerative Disorders ◽  
Microglial Activation ◽  
Neuronal Damage ◽  
Neuronal Survival ◽  
Microglial Cells ◽  
Neuroprotective Effects ◽  
Bv2 Cells ◽  
Parkinson’S Diseases ◽  
Cox 2 ◽  
Bv2 Microglial Cells

Background.Microglial activation contributes to neuroinflammation and neuronal damage in neurodegenerative disorders including Alzheimer’s and Parkinson’s diseases. It has been suggested that neurodegenerative disorders may be improved if neuroinflammation can be controlled.trans-cinnamaldehyde (TCA) isolated from the stem bark ofCinnamomum cassiapossesses potent anti-inflammatory capability; we thus tested whether TCA presents neuroprotective effects on improving neuronal survival by inhibiting neuroinflammatory responses in BV2 microglial cells.Results.To determine the molecular mechanism behind TCA-mediated neuroprotective effects, we assessed the effects of TCA on lipopolysaccharide- (LPS-) induced proinflammatory responses in BV2 microglial cells. While LPS potently induced the production and expression upregulation of proinflammatory mediators, including NO, iNOS, COX-2, IL-1β, and TNF-α, TCA pretreatment significantly inhibited LPS-induced production of NO and expression of iNOS, COX-2, and IL-1βand recovered the morphological changes in BV2 cells. TCA markedly attenuated microglial activation and neuroinflammation by blocking nuclear factor kappa B (NF-κB) signaling pathway. With the aid of microglia and neuron coculture system, we showed that TCA greatly reduced LPS-elicited neuronal death and exerted neuroprotective effects.Conclusions.Our results suggest that TCA, a natural product, has the potential of being used as a therapeutic agent against neuroinflammation for ameliorating neurodegenerative disorders.

Relationship between insulin resistance and inflammatory markers and anti-inflammatory effect of losartan in patients with type 2 diabetes and hypertension

2006 ◽  
Vol 374 (1-2) ◽  
pp. 129-134 ◽  
Author(s):  
Hyohun Park ◽  
Goji Hasegawa ◽  
Hiroshi Obayashi ◽  
Aya Fujinami ◽  
Mitsuhiro Ohta ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Inflammatory Markers ◽  
Anti Inflammatory ◽  
Inflammatory Effect

scholarly journals Characterization of Endocannabinoid System and Interleukin Profiles in Ovine AEC: Cannabinoid Receptors Type-1 and Type-2 as Key Effectors of Pro-Inflammatory Response

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 1008 ◽  
Author(s):  
Luana Greco ◽  
Valentina Russo ◽  
Cinzia Rapino ◽  
Clara Di Germanio ◽  
Filomena Fezza ◽  
...  
Keyword(s):  
Immune Modulation ◽  
Cannabinoid Receptors ◽  
Endocannabinoid System ◽  
Middle Stage ◽  
Selective Agonists ◽  
Anti Inflammatory

Amniotic epithelial cells (AEC) have been proposed as promising clinical candidates for regenerative medicine therapies due to their immunomodulatory capacity. In this context, the endocannabinoid system (ECS) has been identified as mediating the immune-stem cell dialogue, even if no information on AEC is available to date. Therefore, this study was designed to assess whether ECS is involved in tuning the constitutive and lipopolysaccharide (LPS)-induced ovine AEC anti-inflammatory and pro-inflammatory interleukin (IL-10, IL-4, and IL-12) profiles. Firstly, interleukins and ECS expressions were studied at different stages of gestation. Then, the role of cannabinoid receptors 1 and 2 (CB1 and CB2) on interleukin expression and release was investigated in middle stage AEC using selective agonists and antagonists. AEC displayed a degradative more than a synthetic endocannabinoid metabolism during the early and middle stages of gestation. At the middle stage, cannabinoid receptors mediated the balance between pro-inflammatory (IL-12) and anti-inflammatory (IL-4 and IL-10) interleukins. The activation of both receptors mediated an overall pro-inflammatory shift—CB1 reduced the anti-inflammatory and CB2 increased the pro-inflammatory interleukin release, particularly after LPS stimulation. Altogether, these data pave the way for the comprehension of AEC mechanisms tuning immune-modulation, crucial for the development of new AEC-based therapy protocols.

scholarly journals The role of prolactin in central nervous system inflammation

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Edgar Ramos-Martinez ◽  
Ivan Ramos-Martínez ◽  
Gladys Molina-Salinas ◽  
Wendy A. Zepeda-Ruiz ◽  
Marco Cerbon
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neuronal Damage ◽  
Neurological Diseases ◽  
Neuroprotective Effect ◽  
General Information ◽  
Experimental Models ◽  
Neuroprotective Effects ◽  
Anti Inflammatory

Abstract Prolactin has been shown to favor both the activation and suppression of the microglia and astrocytes, as well as the release of inflammatory and anti-inflammatory cytokines. Prolactin has also been associated with neuronal damage in diseases such as multiple sclerosis, epilepsy, and in experimental models of these diseases. However, studies show that prolactin has neuroprotective effects in conditions of neuronal damage and inflammation and may be used as neuroprotector factor. In this review, we first discuss general information about prolactin, then we summarize recent findings of prolactin function in inflammatory and anti-inflammatory processes and factors involved in the possible dual role of prolactin are described. Finally, we review the function of prolactin specifically in the central nervous system and how it promotes a neuroprotective effect, or that of neuronal damage, particularly in experimental autoimmune encephalomyelitis and during excitotoxicity. The overall studies indicated that prolactin may be a promising molecule for the treatment of some neurological diseases.

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