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Although there is increasing evidence that blood‐derived macrophages support tumor progression, it is still unclear whether specialized resident macrophages, such as brain microglia, also play a prominent role in metastasis formation. Here, we show that microglia enhance invasion and colonization of brain tissue by breast cancer cells, serving both as active transporters and guiding rails. This is...
Experimental autoimmune encephalomyelitis (EAE) is a T cell‐mediated neuroinflammatory disease that is often used as a model of multiple sclerosis. EAE can follow either relapsing‐remitting (RR) or chronic (CH) courses, yet the factors responsible for differentially inducing these forms of disease remain largely unknown. Proinflammatory cytokines play an important role in EAE, and signaling by these...
Apoptosis is a controlled cell‐death process mediated inter alia by proteins of the Bcl‐2 family. Some proteins previously shown to promote the apoptotic process were found to have nonapoptotic functions as well. Microglia, the resident immune cells of the central nervous system, respond to brain derangements by becoming activated to contend with the brain damage. Activated microglia can also undergo...
Several neurodegenerative diseases are influenced by the innate immune response in the central nervous system (CNS). Microglia have proinflammatory and subsequently neurotoxic actions as well as anti‐inflammatory functions that promote recovery and repair. Very little is known about the transcriptional control of these specific microglial behaviors. We have previously shown that in HIV‐associated...
Neuroaxonal degeneration is a pathological hallmark of multiple sclerosis (MS) contributing to irreversible neurological disability. Pathological mechanisms leading to axonal damage include autoimmunity to neuronal antigens. In actively demyelinating lesions, myelin is phagocytosed by microglia and blood‐borne macrophages, whereas the fate of degenerating or damaged axons is unclear. Phagocytosis...
Microglia, macrophages of the central nervous system, play an important role in brain homeostasis. Their origin has been unclear. Recent fate‐mapping experiments have established that microglia mostly originate from Myb‐independent, FLT3‐independent, but PU.1‐dependent precursors that express the CSF1‐receptor at E8.5 of embryonic development. These precursors are presumably located in the yolk sac...
MicroRNAs (miRNAs) are a class of small (∼22 nucleotides) noncoding RNAs involved in the regulation of gene expression at the post‐translational level. It is estimated that 30–90% of human genes are regulated by miRNAs, which makes these molecules of great importance for cell growth, activation, and differentiation. Microglia is CNS‐resident cells of a myeloid lineage that play an important role in...
Neuroinflammation perpetuates neuronal damage in many neurological disorders. Activation of resident microglia and infiltration of monocytes/macrophages contributes to neuronal injury and synaptic damage. Noninvasive imaging of these cells in vivo provides a means to monitor progression of disease as well as assess efficacies of potential therapeutics. This review provides an overview of positron...
Microglia, the innate immune cells of the brain, plays a central role in cerebral listeriosis. Here, we present evidence that microglia control Listeria infection differently than macrophages. Infection of primary microglial cultures and murine cell lines with Listeria resulted in a dual function of the two gene expression programmes involved in early and late immune responses in macrophages. Whereas...
Macrophage can adopt several phenotypes, process call polarization, which is crucial for shaping inflammatory responses to injury. It is not known if microglia, a resident brain macrophage population, polarizes in a similar way, and whether specific microglial phenotypes modulate cell death in response to brain injury. In this study, we show that both BV2‐microglia and mouse bone marrow derived macrophages...
Microglia are resident antigen‐presenting cells in the central nervous system (CNS) that either suppress or promote disease depending on their activation phenotype and the microenvironment. Multiple sclerosis (MS) is a chronic inflammatory disease causing demyelination and nerve loss in the CNS, and experimental autoimmune encephalomyelitis (EAE) is an animal model of MS that is widely used to investigate...
Macrophage activation and persistent inflammation contribute to the pathological process of spinal cord injury (SCI). It was reported that M2 macrophages were induced at 3–7 days after SCI but M2 markers were reduced or eliminated after 1 week. By contrast, M1 macrophage response is rapidly induced and then maintained at injured spinal cord. However, factors that modulate macrophage phenotype and...
Infarcted regions of the brain after stroke are segregated from the intact brain by scar tissue comprising both fibrous and glial components. The extent and quality of scarring is influenced by inflammation. The matricellular glycoprotein osteopontin (OPN) is strongly induced in myeloid cells after stroke and may contribute to repair of ischemic brain lesions. To elucidate the role of OPN in scar...
Traumatic brain injury (TBI) is a major cause of death and disability. The underlying pathophysiology is characterized by secondary processes including neuronal death and gliosis. To elucidate the role of the NG2 proteoglycan we investigated the response of NG2‐knockout mice (NG2‐KO) to TBI. Seven days after TBI behavioral analysis, brain damage volumetry and assessment of blood brain barrier integrity...
Under stressful conditions nucleotides are released from dying cells into the extracellular space, where they can bind to purinergic P2X and P2Y receptors. High concentrations of extracellular ATP in particular induce P2X7‐mediated signaling, which leads to inflammasome activation. This in turn leads to the processing and secretion of pro‐inflammatory cytokines, like interleukin (IL)−1β. During neurodegenerative...
Na+/H+ exchanger (NHE1) activation is required for multiple microglial functions. We investigated effects of selective deletion of microglial Nhe1 in Cx3cr1‐CreER;Nhe1f/f mice on neuroinflammation and tissue repair after ischemic stroke. Infarct volume was similar in corn oil or tamoxifen (Tam)‐treated mice at 48 hr and 14 days post‐stroke. However, the Tam‐treated mice showed significantly higher...
Ischemic brain injury causes local inflammation, which involves activation of resident microglia, leukocyte, and monocyte infiltration. Involvement of peripheral immune cells in ischemia‐induced damage and repair is debatable. Using flow cytometry, gene expression profiling, and immunocytochemistry, we show that microglia predominate in the ischemic brain and express inflammation mediators at Day...
Microglia are the resident tissue macrophages of the central nervous system including the retina. Under pathophysiological conditions, microglia can signal to Müller cells, the major glial component of the retina, affecting their morphological, molecular, and functional responses. Microglia–Müller cell interactions appear to be bidirectional shaping the overall injury response in the retina. Hence,...
Numerous recent studies have been performed to elucidate the function of microglia, macrophages, and astrocytes in inflammatory diseases of the central nervous system. Regarding myeloid cells a core pattern of activation has been identified, starting with the activation of resident homeostatic microglia followed by recruitment of blood borne myeloid cells. An initial state of proinflammatory activation...
Satellite glial cells (SGCs) are homeostatic cells enveloping the somata of peripheral sensory and autonomic neurons. A wide variety of neuronal stressors trigger activation of SGCs, contributing to, for example, neuropathic pain through modulation of neuronal activity. However, compared to neurons and other glial cells of the nervous system, SGCs have received modest scientific attention and very...
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