Cross-Talk and Subset Control of Microglia and Associated Myeloid Cells in Neurological Disorders (original) (raw)
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Microglia are the primary innate immune cells in the CNS. In the healthy brain, they exhibit a unique molecular homeostatic 'signature', consisting of a specific transcriptional profile and surface protein expression pattern, which differs from that of tissue macrophages. In recent years, there have been a number of important advances in our understanding of the molecular signatures of homeostatic microglia and disease-associated microglia that have provided insight into how these cells are regulated in health and disease and how they contribute to the maintenance of the neural environment. Our understanding of the origin and functions of microglia has grown to such an extent that it is as if a new CNS cell has been described 1-5. These advances have major implications for understanding normal CNS function and have opened up new avenues to understand the role of microglia in disease. Most importantly, they have created the opportunity to consider ways in which microglia may be imaged and targeted for the treatment of disease.
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The last two decades has witnessed many achievements in our understanding of the molecular-mechanisms underlying various neuroinflammatory-disorders. Microglia activation is thought to be a driving force of neurodegeneration that follows neuroinflammation in many neurological disorders, but confirmatory evidence is still elusive. In particular, the possible relationship between cause and consequence for microglia activation and pathological landmarks, such as neuronal demyelination and cell death in adult vs neonatal age is still disputed. In this thesis we tried to highlight the potential of early biomarkers for microglia-activation, using two rat models of diseases where microglia activation and neurodegeneration interact. In the paper included in chapter I, we performed a time-course investigation of neuroinflammation and demyelination biomarkers in the spinal cord, cerebrospinal fluid and blood in EAE induced in Dark-Agouti female rats compared with controls and adjuvant, focusi...
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Microglia are the principal resident immune cells in the central nervous system and are believed to be versatile players in both inflammatory and physiological contexts. On the one hand, in order to safeguard the microenvironment microglia can be rapidly activated by contact with microbial products or cell debris, thereby exerting the functions of innate immunity via phagocytosis and secretion of cytokines and chemokines. Conversely, microglia can also assist in brain development, synaptic plasticity and neural repair through the production of neurotrophic factors and clearance of myelin debris. It is now well accepted that the dysfunction of microglia and microglia-induced neuroinflammation are implicated in the occurrence and progression of many neurological diseases. Although the past decade has witnessed major progress in understanding of multi-tasking microglia, what remains largely enigmatic is the relative importance of microglia at different disease stages and how microglia ...
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At the frontier between immunology and neuroscience, microglia, the enigmatic macrophages of the brain, have generated, in recent years, increasing interest. In response to even minor pathological changes in the brain, these extremely versatile glial cells occasionally enter in an over-activating state and produce pro-inflammatory cytokines and free radicals, thereby contributing directly to neuroinflammation and various brain disorders. This review provides an analysis of the latest developments in the microglia field, considering the important new research that illustrate their involvement in brain related diseases.
Neuroinflammation and m2 microglia
The concept of multiple macrophage activation states is not new. However, extending this idea to resident tissue macrophages, like microglia, has gained increased interest in recent years. Unfortunately, the research on peripheral macrophage polarization does not necessarily translate accurately to their central nervous system (CNS) counterparts. Even though pro- and anti-inflammatory cytokines can polarize microglia to distinct activation states, the specific functions of these states is still an area of intense debate. This review examines the multiple possible activation states microglia can be polarized to. This is followed by a detailed description of microglial polarization and the functional relevance of this process in both acute and chronic CNS disease models described in the literature. Particular attention is given to utilizing M2 microglial polarization as a potential therapeutic option in treating diseases.