Search results for "Microglia"

Neuronal injury in chronic CNS inflammation.

2010

Introduction Multiple sclerosis (MS) is the most common chronic inflammatory disease of the central nervous system which is characterized by inflammatory demyelination and neurodegeneration. Neurological symptoms include sensory disturbances, optic neuritis, limb weakness, ataxia, bladder dysfunction, cognitive deficits and fatigue. Pathophysiology The inflammation process with MS is promoted by several inflammatory cytokines produced by the immune cells themselves and local resident cells like activated microglia. Consecutive damaging pathways involve the transmigration of activated B lymphocytes and plasma cells, which synthesize antibodies against the myelin sheath, boost the immune atta…

Demyelination patterns in a mathematical model of multiple sclerosis.

2016

In this paper we derive a reaction-diffusion-chemotaxis model for the dynamics of multiple sclerosis. We focus on the early inflammatory phase of the disease characterized by activated local microglia, with the recruitment of a systemically activated immune response, and by oligodendrocyte apoptosis. The model consists of three equations describing the evolution of macrophages, cytokine and apoptotic oligodendrocytes. The main driving mechanism is the chemotactic motion of macrophages in response to a chemical gradient provided by the cytokines. Our model generalizes the system proposed by Calvez and Khonsari (Math Comput Model 47(7–8):726–742, 2008) and Khonsari and Calvez (PLos ONE 2(1):e…

Anomalous alterations affecting microglia in the central nervous system of a fetus at 12 weeks of gestation: case report.

2003

We report here on the first documented case of profound alterations specifically affecting the microglial population within the nervous system during the fetal period. This case, derived at gestational week 12, was one amongst a series of second trimester brains currently being investigated with respect to microglial colonization of the human fetal brain. No significant pathological alterations could be identified upon gross macroscopy or following microscopic analysis of serial brain sections stained with cresyl fast violet (Nissl). By contrast, sections stained immunohistochemically to detect MHC class II (CR3/43) and CD68 (PG-M1) antigens revealed a marked pathological change in the morp…

2013

In the nervous system, glia cells maintain homeostasis, synthesize myelin, provide metabolic support, and participate in immune defense. The communication between glia and neurons is essential to synchronize these diverse functions with brain activity. Evidence is accumulating that secreted extracellular vesicles (EVs), such as exosomes and shedding microvesicles, are key players in intercellular signaling. The cells of the nervous system secrete EVs, which potentially carry protein and RNA cargo from one cell to another. After delivery, the cargo has the ability to modify the target cell phenotype. Here, we review the recent advances in understanding the role of EV secretion by astrocytes,…

NG2-expressing cells in the nervous system revealed by the NG2-EYFP-knockin mouse.

2008

The NG2 glycoprotein is a type I membrane protein expressed by immature cells in the developing and adult mouse. NG2+ cells of the embryonic and adult brain have been principally viewed as oligodendrocyte precursor cells but have additionally been considered a fourth glial class. They are likely to be a heterogeneous population. In order to facilitate studies on the function of NG2+ cells and to characterize these cells in situ, we generated an enhanced yellow fluorescent protein (EYFP) “knockin mouse.” EYFP-expressing cells in heterozygous knockin mice expressed the NG2 protein in all regions and at all ages studied. The EYFP+ cells did not express markers of mature glia, developing or mat…

Adult Neural Stem Cells Are Alerted by Systemic Inflammation through TNF-α Receptor Signaling.

2021

Summary Adult stem cells (SCs) transit between the cell cycle and a poorly defined quiescent state. Single neural SCs (NSCs) with quiescent, primed-for-activation, and activated cell transcriptomes have been obtained from the subependymal zone (SEZ), but the functional regulation of these states under homeostasis is not understood. Here, we develop a multilevel strategy to analyze these NSC states with the aim to uncover signals that regulate their level of quiescence/activation. We show that transitions between states occur in vivo and that activated and primed, but not quiescent, states can be captured and studied in culture. We also show that peripherally induced inflammation promotes a …

Homeostasis of Microglia in the Adult Brain: Review of Novel Microglia Depletion Systems.

2015

Microglia are brain macrophages that emerge from early erythro-myeloid precursors in the embryonic yolk sac and migrate to the brain mesenchyme before the blood brain barrier is formed. They seed the brain, and proliferate until they have formed a grid-like distribution in the central nervous system that is maintained throughout lifespan. The mechanisms through which these embryonic-derived cells contribute to microglia homoeostasis at steady state and upon inflammation are still not entirely clear. Here we review recent studies that provided insight into the contribution of embryonically-derived microglia and of adult 'microglia-like' cells derived from monocytes during inflammation. We ex…

Treatment with Nicotine derived Nitrosamine Ketone NNK Causes Disruption of Blood Brain Barrier BBB and Microglia Activation in Mice

2022

4-Methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK) is a nicotine metabolite produced within the tobacco plant, from combustion, and from metabolic breakdown. Cigarette Smoke (CS) continues to be a leading cause for decline of quality of life as well as deaths globally. While the link to poor health and eventually early death has been accepted for decades, it is increasingly recognized that smoking may contribute to a broad range of disorders. Epidemiologically, CS has been associated with neuroinflammation and several neurological disorders including Alzheimer’s disease, stroke, and multiple sclerosis. While direct links are not fully understood, studies in a humanized flow-based in vitro b…

Oligodendrocyte ablation triggers central pain independently of innate or adaptive immune responses in mice.

2014

Mechanisms underlying central neuropathic pain are poorly understood. Although glial dysfunction has been functionally linked with neuropathic pain, very little is known about modulation of pain by oligodendrocytes. Here we report that genetic ablation of oligodendrocytes rapidly triggers a pattern of sensory changes that closely resemble central neuropathic pain, which are manifest before overt demyelination. Primary oligodendrocyte loss is not associated with autoreactive T- and B-cell infiltration in the spinal cord and neither activation of microglia nor reactive astrogliosis contribute functionally to central pain evoked by ablation of oligodendrocytes. Instead, light and electron micr…

In the literature: April 2019

2019

Glioblastoma (GBM) remains an unmet need in Medical Oncology considering its poor prognosis and the lack of advances in therapeutics in more than one decade.1 Despite the initial enthusiasm, the development of immunotherapy in GBM has proved to be challenging, with a disappointing negative phase III clinical trial.2 Some of the phenotypic hallmarks of GBM make immunotherapy difficult. Its relatively low mutational load, its immunologically ‘cold’ microenvironment with scarce infiltrating immune effector cells, a dominant myeloid compartment composed by microglia and myeloid-derived suppressor cells and a strong immunosuppression, both local, mediated by immunosuppressive regulatory T cells …