Renin-Angiotensin System: Updated Understanding and Role in Physiological and Pathophysiological States.

The classical view of the renin-angiotensin system (RAS) is that of the circulating hormone pathway involved in salt and water homeostasis and blood pressure regulation. It is also involved in the pathogenesis of cardiac and renal disorders. This led to the creation of drugs blocking the actions of this classical pathway, which improved cardiac and renal outcomes.

Activation of neuronal NADPH oxidase NOX2 promotes inflammatory neurodegeneration.

Strong evidence indicates critical roles of NADPH oxidase (a key superoxide-producing enzyme complex during inflammation) in activated microglia for mediating neuroinflammation and neurodegeneration. However, little is known about roles of neuronal NADPH oxidase in neurodegenerative diseases. This study aimed to investigate expression patterns, regulatory mechanisms and pathological roles of neuronal NADPH oxidase in inflammation-associated neurodegeneration.

Annexin-A1 Tripeptide Attenuates Surgery-Induced Neuroinflammation and Memory Deficits Through Regulation the NLRP3 Inflammasome.

Neuroinflammation is a growing hallmark of perioperative neurocognitive disorders (PNDs), including delirium and longer-lasting cognitive deficits. We have developed a clinically relevant orthopedic mouse model to study the impact of a common surgical procedure on the vulnerable brain. The mechanism underlying PNDs remains unknown.

URMC-099 prophylaxis prevents hippocampal vascular vulnerability and synaptic damage in an orthopedic model of delirium superimposed on dementia.

Systemic perturbations can drive a neuroimmune cascade after surgical trauma, including affecting the blood-brain barrier (BBB), activating microglia, and contributing to cognitive deficits such as delirium. Delirium superimposed on dementia (DSD) is a particularly debilitating complication that renders the brain further vulnerable to neuroinflammation and neurodegeneration, albeit these molecular mechanisms remain poorly understood. Here, we have used an orthopedic model of tibial fracture/fixation in APPSwDI/mNos2 AD (CVN-AD) mice to investigate relevant pathogenetic mechanisms underlying DSD.

Neuroinflammation after surgery: from mechanisms to therapeutic targets.

Injury is a key driver of inflammation, a critical yet necessary response involving several mediators that is aimed at restoring tissue homeostasis. Inflammation in the central nervous system can be triggered by a variety of stimuli, some intrinsic to the brain and others arising from peripheral signals. Fine-tuned regulation of this response is crucial in a system that is vulnerable due to, for example, aging and ongoing neurodegeneration.

Neurovascular and immune mechanisms that regulate postoperative delirium superimposed on dementia.

Objective: The present work evaluates the relationship between postoperative immune and neurovascular changes and the pathogenesis of surgery-induced delirium superimposed on dementia.

Background And Rationale: Postoperative delirium is a common complication in many older adults and in patients with dementia including Alzheimer's disease (AD). The course of delirium can be particularly debilitating, while its pathophysiology remains poorly defined.

Orthopedic Surgery Triggers Attention Deficits in a Delirium-Like Mouse Model.

Postoperative delirium is a frequent and debilitating complication, especially amongst high risk procedures such as orthopedic surgery, and its pathogenesis remains unclear. Inattention is often reported in the clinical diagnosis of delirium, however limited attempts have been made to study this cognitive domain in preclinical models. Here we implemented the 5-choice serial reaction time task (5-CSRTT) to evaluate attention in a clinically relevant mouse model following orthopedic surgery.

The tiliroside derivative, 3-O-[(E)-(2-oxo-4-(p-tolyl) but-3-en-1-yl] kaempferol produced inhibition of neuroinflammation and activation of AMPK and Nrf2/HO-1 pathways in BV-2 microglia.

Neuroinflammation is now widely accepted as an important pathophysiological mechanism in neurodegenerative disorders, thus providing a critical target for novel compounds. In this study, 3-O-[(E)-(2-oxo-4-(p-tolyl)but-3-en-1-yl] kaempferol (OTBK) prevented the production of pro-inflammatory mediators TNFα, IL-6, PGE and nitrite from BV-2 microglia activated with LPS and IFNγ. These effects were accompanied by reduction in the levels of pro-inflammatory proteins COX-2 and iNOS.

Induction of Neuroinflammation and Neurotoxicity by Synthetic Hemozoin.

Hemozoin produced by Plasmodium falciparum during malaria infection has been linked to the neurological dysfunction in cerebral malaria. In this study, we determined whether a synthetic form of hemozoin (sHZ) produces neuroinflammation and neurotoxicity in cellular models. Incubation of BV-2 microglia with sHZ (200 and 400 µg/ml) induced significant elevation in the levels of TNFα, IL-6, IL-1β, NO/iNOS, phospho-p65, accompanied by an increase in DNA binding of NF-κB.

Chemical Compositions of Metals in Bhasmas and Tibetan Zuotai Are a Major Determinant of Their Therapeutic Effects and Toxicity.

Minerals are alchemically processed as Bhasmas in Ayurvedic medicines or as Zuotai in Tibetan medicines. Ayurveda is a knowledge system of longevity and considers the mineral elixir made from "nature" capable of giving humans perpetual life. Herbo-metallic preparations have a long history in the treatment of various diseases in India, China, and around the world.

Agathisflavone isolated from Anacardium occidentale suppresses SIRT1-mediated neuroinflammation in BV2 microglia and neurotoxicity in APPSwe-transfected SH-SY5Y cells.

Agathisflavone is a bioactive compound in Anacardium occidentale. In this study, we investigated inhibition neuroinflammation in BV2 microglia by agathisflavone. Neuroprotective activity of the compound was investigated in differentiated SH-SY5Y cells.

Activation of Nrf2 Pathway Contributes to Neuroprotection by the Dietary Flavonoid Tiliroside.

Hyperactivated microglia plays a key role in regulating neuroinflammatory responses which cause damage to neurons. In recent years, substantial attention has been paid in identifying new strategies to abrogate neuroinflammation. Tiliroside, a natural dietary glycosidic flavonoid, is known to inhibit neuroinflammation.

AMPK and SIRT1 activation contribute to inhibition of neuroinflammation by thymoquinone in BV2 microglia.

Thymoquinone is a known inhibitor of neuroinflammation. However, the mechanism(s) involved in its action remain largely unknown. In this study, we investigated the roles of cellular reactive oxygen species (ROS), 5' AMP-activated protein kinase (AMPK) and sirtuin 1 (SIRT1) in the anti-neuroinflammatory activity of thymoquinone.

Inhibition of neuroinflammation by thymoquinone requires activation of Nrf2/ARE signalling.

Thymoquinone is an antioxidant phytochemical that has been shown to inhibit neuroinflammation. However, little is known about the potential roles of intracellular antioxidant signalling pathways in its anti-inflammatory activity. The objective of this study was to elucidate the roles played by activation of the Nrf2/ARE antioxidant mechanisms in the anti-inflammatory activity of this compound.

Antimalarial Drug Artemether Inhibits Neuroinflammation in BV2 Microglia Through Nrf2-Dependent Mechanisms.

Artemether, a lipid-soluble derivative of artemisinin has been reported to possess anti-inflammatory properties. In this study, we have investigated the molecular mechanisms involved in the inhibition of neuroinflammation by the drug. The effects of artemether on neuroinflammation-mediated HT22 neuronal toxicity were also investigated in a BV2 microglia/HT22 neuron co-culture.

Inhibition of neuroinflammation in BV2 microglia by the biflavonoid kolaviron is dependent on the Nrf2/ARE antioxidant protective mechanism.

Kolaviron is a mixture of biflavonoids found in the nut of the West African edible seed Garcinia kola, and it has been reported to exhibit a wide range of pharmacological activities. In this study, we investigated the effects of kolaviron in neuroinflammation. The effects of kolaviron on the expression of nitric oxide/inducible nitric oxide synthase (iNOS), prostaglandin E2 (PGE2)/cyclooxygenase-2, cellular reactive oxygen species (ROS) and the pro-inflammatory cytokines were examined in lipopolysaccharide (LPS)-stimulated BV2 microglial cells.

Pomegranate inhibits neuroinflammation and amyloidogenesis in IL-1β-stimulated SK-N-SH cells.

Purpose: Pomegranate fruit, Punica granatum L. (Punicaceae), and its constituents have been shown to inhibit inflammation. In this study, we aimed to assess the effects of freeze-dried pomegranate (PWE) on PGE2 production in IL-1β-stimulated SK-N-SH cells.

Tiliroside, a dietary glycosidic flavonoid, inhibits TRAF-6/NF-κB/p38-mediated neuroinflammation in activated BV2 microglia.

Background: Tiliroside is a dietary glycosidic flavonoid which has shown in vivo anti-inflammatory activity. This study is aimed at evaluating the effect of tiliroside on neuroinflammation in BV2 microglia, and to identify its molecular targets of anti-neuroinflammatory action.

Methods: BV2 cells were stimulated with LPS+IFNγ in the presence or absence of tiliroside.

Punicalagin inhibits neuroinflammation in LPS-activated rat primary microglia.

Scope: In this study, the effects of punicalagin on neuroinflammation in LPS-activated microglia were investigated.

Methods And Results: The ability of punicalagin to reduce the production of TNF-α, IL-6 and prostaglandin E2 was measured in culture medium using enzyme immunoassay. TNF-α and IL-6 gene expression in mouse hippocampal slices was measured with PCR.

Picralima nitida seeds suppress PGE2 production by interfering with multiple signalling pathways in IL-1β-stimulated SK-N-SH neuronal cells.

Ethnopharmacological Relevance: The dried seed of Picralima nitida is used in rheumatic fever and as an antipyretic in West Africa. In this study we have investigated the effects of an extract obtained from the seeds of Picralima nitida (PNE) on PGE2 production in IL-1β-stimulated cells.

Materials And Methods: Prostaglandin E2 (PGE2) was measured in supernatants of IL-1β-stimulated SK-N-SH cells using enzyme immunoassay (EIA) for PGE2.