Inflammation and Stroke: An Overview

Neurotherapeutics, Год журнала: 2016, Номер 13(4), С. 661 - 670

Опубликована: Окт. 1, 2016

Язык: Английский

---

Microglia monitor and protect neuronal function through specialized somatic purinergic junctions

Science, Год журнала: 2019, Номер 367(6477), С. 528 - 537

Опубликована: Дек. 13, 2019

Microglia are the main immune cells in brain and have roles homeostasis neurological diseases. Mechanisms underlying microglia-neuron communication remain elusive. Here, we identified an interaction site between neuronal cell bodies microglial processes mouse human brain. Somatic junctions a specialized nanoarchitecture optimized for purinergic signaling. Activity of mitochondria was linked with junction formation, which induced rapidly response to activation blocked by inhibition P2Y12 receptors. Brain injury-induced changes at somatic triggered receptor-dependent neuroprotection, regulating calcium load functional connectivity. Thus, these could potentially monitor protect functions.

Язык: Английский

---

Microglia are an essential component of the neuroprotective scar that forms after spinal cord injury

Nature Communications, Год журнала: 2019, Номер 10(1)

Опубликована: Янв. 31, 2019

Abstract The role of microglia in spinal cord injury (SCI) remains poorly understood and is often confused with the response macrophages. Here, we use specific transgenic mouse lines depleting agents to understand after SCI. We find that are highly dynamic proliferate extensively during first two weeks, accumulating around lesion. There, activated position themselves at interface between infiltrating leukocytes astrocytes, which form a scar microglia-derived factors, such as IGF-1. Depletion SCI causes disruption glial formation, enhances parenchymal immune infiltrates, reduces neuronal oligodendrocyte survival, impairs locomotor recovery. Conversely, increased microglial proliferation, induced by local M-CSF delivery, lesion size functional Altogether, our results identify key cellular component develops protect neural tissue.

Язык: Английский

---

Glial Cells: Role of the Immune Response in Ischemic Stroke

Frontiers in Immunology, Год журнала: 2020, Номер 11

Опубликована: Фев. 26, 2020

Ischemic stroke, which accounts for 75-80% of strokes, is a predominant cause morbidity and mortality worldwide. Recently, post-stroke immune response becomes new breakthrough the treatment strategy ischemic stroke. Glial cells, including microglia, astrocytes, oligodendrocytes, are major components peri-infarction environment in central nervous system have been elucidated to play critical roles regulation. However, increasing evidences suggest that glial cells exert different, even contrary effect Microglia, survey CNS homostasis regulate innate response, rapidly activated following The microglia would release inflammatory cytokines induce neuronal tissue injuries. On contrary, anti-inflammatory neurotrophic factors secreted by alternatively considered be benefit recovery Astrocytes activation reactive gliosis stroke contribute limitaion brain injury stabalize homeostasis. scar developed astrocytes also hinder reconnectivity extension. Oligodendrocytes shown extensively involved demyelination remyelination after Oligodendrocyte precursor able differentiate into reactived supposed lead functional recovery. Here we discuss mechanisms regulation mediated interaction between neurons. present review, from perspective various describes their possible at different stages future intervention targets.

Язык: Английский

---

Glial Cells and Their Function in the Adult Brain: A Journey through the History of Their Ablation

Frontiers in Cellular Neuroscience, Год журнала: 2017, Номер 11

Опубликована: Фев. 13, 2017

Glial cells, consisting of microglia, astrocytes and oligodendrocyte lineage cells as their major components, constitute a large fraction the mammalian brain. Originally considered purely non-functional glue for neurons, decades research have highlighted importance well further functions glial cells. Although many aspects these are characterized nowadays, different populations in brain under both physiological pathological conditions remain, at least to certain extent, unresolved. To tackle important questions, broad range depletion approaches been developed which or (i.e. NG2-glia oligodendrocytes) specifically ablated from adult network with subsequent analysis consequences. As very heterogeneous, it is imperative ablate single cell instead inducing death all general. Thanks modern genetic manipulation methods, can now directly be targeted type interest making ablation more specific compared general that used earlier on. In this review we will give detailed summary on studies, focusing mouse central nervous system (CNS) functional readouts. We also provide an outlook how could exploited future.

Язык: Английский

---

Repopulating Microglia Promote Brain Repair in an IL-6-Dependent Manner

Cell, Год журнала: 2020, Номер 180(5), С. 833 - 846.e16

Опубликована: Март 1, 2020

Язык: Английский

---

Bidirectional Microglia–Neuron Communication in Health and Disease

Frontiers in Cellular Neuroscience, Год журнала: 2018, Номер 12

Опубликована: Сен. 27, 2018

Microglia are ramified cells that exhibit highly motile processes, which continuously survey the brain parenchyma and react to any insult CNS homeostasis. Although microglia have long been recognized as a crucial player in generating maintaining inflammatory responses CNS, now it has become clear, their function much more diverse, particularly healthy brain. The innate immune response phagocytosis represent only little segment of functional repertoire also includes maintenance biochemical homeostasis, neuronal circuit maturation during development experience- dependent remodeling circuits adult Being equipped by numerous receptors cell surface molecules can perform bidirectional interactions with other types CNS. There is accumulating evidence showing neurons inform about status thus capable controlling microglial activation motility while modulate activities. This review addresses topic: how communicate brain, including fractalkine signaling, secreted soluble factors extracellular vesicles. We summarize current state knowledge physiological role mature further highlight contribution pathologies such Alzheimer's Parkinson's disease, ischemia, traumatic injury, tumour well neuropsychiatric diseases (depression, bipolar disorder schizophrenia).

Язык: Английский

---

Microglial Activation in Traumatic Brain Injury

Frontiers in Aging Neuroscience, Год журнала: 2017, Номер 9

Опубликована: Июнь 28, 2017

Microglia have a variety of functions in the brain, including synaptic pruning, CNS repair and is involved mediating immune response against peripheral infection. rapidly become activated to damage. Depending on nature stimulus, microglia can take number activation states, which correspond altered morphology, gene expression function. It has been reported that early following traumatic brain injury (TBI) may contribute restoration homeostasis brain. On other hand, if they remain chronically activated, such cells display classically phenotype, releasing pro-inflammatory molecules, resulting further tissue damage contributing potentially neurodegeneration. However, new evidence suggests this classification over-simplistic balance states vary at different points. In article, we review role TBI, analysing their distribution, morphology functional phenotype over time animal models humans. Animal studies allowed genetic pharmacological manipulations activation, order define role. addition, describe investigations vivo imaging using translocator protein (TSPO) PET autoradiography, showing microglial occur regions far remote from sites focal injuries, humans TBI. Finally, outline some novel potential therapeutic approaches prime microglia/macrophages toward beneficial restorative after

Язык: Английский

---

Microglia in Neuroinflammation and Neurodegeneration: From Understanding to Therapy

Frontiers in Neuroscience, Год журнала: 2021, Номер 15

Опубликована: Сен. 24, 2021

Microglia are the resident macrophages of central nervous system (CNS) acting as first line defense in brain by phagocytosing harmful pathogens and cellular debris. emerge from early erythromyeloid progenitors yolk sac enter developing before establishment a fully mature blood–brain barrier. In physiological conditions, during development, microglia contribute to CNS homeostasis supporting cell proliferation neural precursors. post-natal life, such cells preserving integrity neuronal circuits sculpting synapses. After injury, change their morphology down-regulate those genes homeostatic functions. However, it is still unclear whether changes accompanied molecular functional modifications that might pathological process. While comprehensive transcriptome analyses at single-cell level have identified specific gene perturbations occurring “pathological” microglia, precise protective/detrimental role neurological disorders far being elucidated. this review, results so obtained regarding neurodegenerative will be discussed. There solid sound evidence suggesting regulating functions disease pathology represent strategy develop future therapies aimed counteracting degeneration multiple sclerosis, Alzheimer’s disease, Parkinson’s amyotrophic lateral sclerosis.

Язык: Английский

---

Early long-term administration of the CSF1R inhibitor PLX3397 ablates microglia and reduces accumulation of intraneuronal amyloid, neuritic plaque deposition and pre-fibrillar oligomers in 5XFAD mouse model of Alzheimer’s disease

Molecular Neurodegeneration, Год журнала: 2018, Номер 13(1)

Опубликована: Март 1, 2018

Besides the two main classical features of amyloid beta aggregation and tau-containing neurofibrillary tangle deposition, neuroinflammation plays an important yet unclear role in pathophysiology Alzheimer's disease (AD). Microglia are believed to be key mediators during AD responsible for regulation brain homeostasis by balancing neurotoxicity neuroprotective events. We have previously reported evidence that neuritic plaques derived from dead neurons accumulated intraneuronal further recruit Iba1-positive cells, which play a either neuronal demise or plaque maturation both. To study impact microglia on development, we treated two-month-old 5XFAD mice with selective colony stimulation factor 1 receptor (CSF1R) inhibitor, PLX3397, period 3 months, resulting significant ablation microglia. Directly after this treatment, analyzed amount performed behavioral studies including Y-maze, fear conditioning elevated plus maze. found early long-term PLX3397 administration results dramatic reduction both as well deposition. young also displayed decrease soluble fibrillar oligomers lysates, depletion pre-fibrillar plasma improvement cognitive function measured tests. Our findings demonstrate CSF1R signaling, directly mediated microglia, is crucial accumulation formation plaques, suggesting these events serially linked causal pathway leading neurodegeneration formation. inhibitors represent potential preventative therapeutic approach target very earliest stages plaques.

Язык: Английский

---