Microglia and Monocytes/Macrophages Polarization Reveal Novel Therapeutic Mechanism against Stroke

International Journal of Molecular Sciences, Journal Year: 2017, Volume and Issue: 18(10), P. 2135 - 2135

Published: Oct. 13, 2017

Stroke is a leading cause of morbidity and mortality worldwide, consists two types, ischemic hemorrhagic. Currently, there no effective treatment to increase the survival rate or improve quality life after hemorrhagic stroke in subacute chronic phases. Therefore, it necessary establish therapeutic strategies facilitate functional recovery patients with during both Cell-based therapies, using microglia monocytes/macrophages preconditioned by optimal stimuli and/or any therapies targeting these cells, might be an ideal strategy for managing stroke. Microglia polarize classic pro-inflammatory type (M1-like) alternative protective (M2-like) condition. M2-like against three reasons. First, monocytes/monocytes secrete remodeling factors, thus prompting neuronal network via tissue (including neuronal) vascular remodeling. Second, cells could migrate injured hemisphere through blood–brain barrier choroid–plexus. Third, mitigate extent inflammation-induced injuries suitable timing intervention. Although future translational studies are required, attractive based on their functions.

Language: Английский

---

Balancing the immune response in the brain: IL-10 and its regulation

Journal of Neuroinflammation, Journal Year: 2016, Volume and Issue: 13(1)

Published: Nov. 23, 2016

The inflammatory response is critical to fight insults, such as pathogen invasion or tissue damage, but if not resolved often becomes detrimental the host. A growing body of evidence places non-resolved inflammation at core various pathologies, from cancer neurodegenerative diseases. It therefore surprising that immune system has evolved several regulatory mechanisms achieve maximum protection in absence pathology.The production anti-inflammatory cytokine interleukin (IL)-10 one most important by many cells counteract damage driven excessive inflammation. Innate central nervous system, notably microglia, are no exception and produce IL-10 downstream pattern recognition receptors activation. However, whereas molecular regulating expression innate acquired periphery have been extensively addressed, our knowledge on modulation much scattered. This review addresses current understanding brain implications disorders.The regulation remains a challenging field. Answering remaining outstanding questions will contribute design targeted approaches aiming controlling deleterious brain.

Language: Английский

---

Astrocytes and Microglia: In Sickness and in Health

Trends in Neurosciences, Journal Year: 2020, Volume and Issue: 43(3), P. 144 - 154

Published: Feb. 7, 2020

Language: Английский

---

Anti-Inflammatory Effects of Omega-3 Fatty Acids in the Brain: Physiological Mechanisms and Relevance to Pharmacology

Pharmacological Reviews, Journal Year: 2017, Volume and Issue: 70(1), P. 12 - 38

Published: Dec. 7, 2017

Classically, polyunsaturated fatty acids (PUFA) were largely thought to be relatively inert structural components of brain, important for the formation cellular membranes. Over past 10 years, a host bioactive lipid mediators that are enzymatically derived from arachidonic acid, main n-6 PUFA, and docosahexaenoic n-3 PUFA in known regulate peripheral immune function, have been detected brain shown microglia activation. Recent advances focused on how molecular signaling microglia, especially context neuroinflammation behavior. Several active drugs provide proof concept targeting brain. Because metabolism relies complex integration diet, metabolism, including liver blood, which supply with PUFAs can altered by genetics, sex, aging, there many pathways disrupted, leading homeostasis. Brain neurologic disorders may viable targets development novel therapeutics. In this study, we discuss particular their metabolites phenotype function exert anti-inflammatory proresolving activities

Language: Английский

---

Sleep Loss Promotes Astrocytic Phagocytosis and Microglial Activation in Mouse Cerebral Cortex

Journal of Neuroscience, Journal Year: 2017, Volume and Issue: 37(21), P. 5263 - 5273

Published: May 24, 2017

We previously found that Mertk and its ligand Gas6 , astrocytic genes involved in phagocytosis, are upregulated after acute sleep deprivation. These results suggested astrocytes may engage phagocytic activity during extended wake, but direct evidence was lacking. Studies humans rodents also loss increases peripheral markers of inflammation, whether these changes associated with neuroinflammation and/or activation microglia, the brain's resident innate immune cells, unknown. Here we used serial block-face scanning electron microscopy to obtain 3D volume measurements synapses surrounding processes mouse frontal cortex 6–8 h sleep, spontaneous or deprivation (SD) chronic (∼5 d) restriction (CSR). Astrocytic mainly presynaptic components large synapses, increased both relative wake. MERTK expression lipid peroxidation synaptoneurosomes a similar extent short long loss, suggesting phagocytosis represent response increase synaptic prolonged clearing worn heavily synapses. Using confocal microscopy, then CSR not SD mice show morphological signs microglial enhanced elements, without obvious CSF. Because low-level sustained microglia can lead abnormal responses secondary insult, suggest through priming, predispose brain further damage. SIGNIFICANCE STATEMENT find mostly origin is already few hours shows significant severe it promote housekeeping strong neuronal By contrast, activates promotes their activity, does so absence overt neuroinflammation, like many other stressors, disruption state activation, perhaps increasing susceptibility forms

Language: Английский

---

Chronic stress as a risk factor for Alzheimer's disease: Roles of microglia-mediated synaptic remodeling, inflammation, and oxidative stress

Neurobiology of Stress, Journal Year: 2018, Volume and Issue: 9, P. 9 - 21

Published: May 19, 2018

Microglia are the predominant immune cells of central nervous system (CNS) that exert key physiological roles required for maintaining CNS homeostasis, notably in response to chronic stress, as well mediating synaptic plasticity, learning and memory. The repeated exposure stress confers a higher risk developing neurodegenerative diseases including sporadic Alzheimer's disease (AD). While microglia have been causally linked amyloid beta (Aβ) accumulation, tau pathology, neurodegeneration, loss AD, they were also attributed beneficial roles, phagocytic elimination Aβ. In this review, we discuss interactions between AD overview played by especially focusing on an environmental factor modulating their function, present recently-described microglial phenotypes associated with neuroprotection AD. These observed under both pathology may provide novel opportunities development better-targeted therapeutic interventions.

Language: Английский

---

Cell-to-cell Communication by Extracellular Vesicles: Focus on Microglia

Neuroscience, Journal Year: 2018, Volume and Issue: 405, P. 148 - 157

Published: April 14, 2018

Extracellular vesicles, including exosomes and microvesicles, are small, nano-to-micrometer vesicles that released from cells. While initially observed in immune cells reticulocytes as meant to remove archaic proteins, now they have been almost all cell types of multicellular organisms. Growing evidence indicates extracellular containing lipids, proteins RNAs, represent an efficient way transfer functional cargoes one another. In the central nervous system, extensive cross-talk ongoing between neurons glia, microglia, brain, takes advantage secreted which mediate intercellular communication over long range distance. Recent literature supports a critical role for mediating complex coordinated among neurons, astrocytes both healthy diseased brain. this review, we focus on biogenesis function microglia-related their putative Alzheimer's disease pathology.

Language: Английский

---

Neuronal network activity controls microglial process surveillance in awake mice via norepinephrine signaling

Nature Neuroscience, Journal Year: 2019, Volume and Issue: 22(11), P. 1771 - 1781

Published: Oct. 21, 2019

Language: Английский

---

Inflammation in Alzheimer’s disease: Lessons learned from microglia-depletion models

Brain Behavior and Immunity, Journal Year: 2016, Volume and Issue: 61, P. 1 - 11

Published: July 7, 2016

Language: Английский

---

Microglia regulation of synaptic plasticity and learning and memory

Neural Regeneration Research, Journal Year: 2021, Volume and Issue: 17(4), P. 705 - 705

Published: Aug. 29, 2021

Microglia are the resident macrophages of central nervous system. possess varied morphologies and functions. Under normal physiological conditions, microglia mainly exist in a resting state constantly monitor their microenvironment survey neuronal synaptic activity. Through C1q, C3 CR3 "Eat Me" CD47 SIRPα "Don't Eat complement pathways, as well other pathways such CX3CR1 signaling, regulate pruning, process crucial for promotion synapse formation regulation activity plasticity. By mediating play an important role experience-dependent plasticity barrel cortex visual after whisker removal or monocular deprivation, also learning memory, including modulation memory strength, forgetfulness, quality. As response to brain injury, infection neuroinflammation, become activated increase number. Activated change amoeboid shape, migrate sites inflammation secrete proteins cytokines, chemokines reactive oxygen species. These molecules released by can lead deficits associated with aging, Alzheimer's disease, traumatic HIV-associated neurocognitive disorder, neurological mental disorders autism, depression post-traumatic stress disorder. With focus on recently published literature, here we reviewed studies investigating how modulate disease-related deficits. summarizing function these processes, aim provide overview discuss possibility manipulation therapeutic ameliorate cognitive disorders.

Language: Английский

---