Trends in Neurosciences
Microglia: a sensor for pathological events in the CNS
Section snippets
The graded response of microglia to injury: the facial-nerve transection model
To define stages of microglia activation in vivo, an animal model which leaves the blood-brain barrier (BBB) unimpaired has proved to be invaluable. After facial-nerve axotomy, the activation of resident microglia can be examined in the absence of infiltrating haematogenous cells. The facial nerve is cut outside the brain and the reactions of facial motoneurones and their glial environment can be studied in the brainstem[7]. After transection of the facial nerve, microglia but not astrocytes
Microglial mitogens
Although proliferation and activation are common reactions of microglia in the injured CNS, little is known about how these processes are regulated in vivo. While several cytokines induce proliferation or phenotypic and morphological changes indicative of activation in vitro, the crucial role of colony-stimulating factors (CSFs) in microglial proliferation has so far been established in vitro and in vivo. CSFs are strong mitogens for microglia in vitro and furthermore influence their
Intracellular signalling and microglia activation
What are the intracellular signals mediating the coupling between short-term, external triggers, such as cytokines or reactive oxygen intermediates, and long-lasting changes of gene expression in activated microglia/macrophages? Transcription factors appear to be differentially involved in these processes. During autoimmune inflammation of the brain in experimental allergic encephalitis (EAE), the transcription factor NFϰB is involved in microglia/macrophage activation as indicated by the early
Opposing functions of activated microglia: protective vs cytotoxic role
Resident microglia play a part in tissue repair after injury, similar to that of resident macrophages in peripheral organs. Synergistic effects of microglia and astrocytes are needed for tissue reconstitution after lesions, involving control of the BBB and of the invasion of haematogenous cells, removal of pro-inflammatory cytokines and their downregulation by TGF-β1. As professional phagocytes they can destroy invading micro-organisms, remove potentially deleterious debris, promote ensuing
Microglia: intrinsic immune system of the CNS?
The brain has a very effective barrier system based on tight junctions at the vasculature, the choroid plexus and the meningeal interfaces that prohibits free access of serum constituents and blood cells to the brain tissue. The brain also lacks a perivascular space and a lymphatic system (except in the transition region to the arachnoidea, and Virchow-Robin spaces). The absence of recognizable expression of molecules of the major histocompatibility complex (MHC) which are decisive for antigen
Intercellular crosstalk between microglia, astrocytes and neurones
Information on signals that mediate the moto-neurone cell-body reaction and the resulting glial-cell response are crucial for our understanding of how regeneration occurs and how the different cell types communicate with each other. Several candidate molecules for this intercellular crosstalk have now been characterized in vivo.
IL1 was initially shown to induce hyperplasia and hypertrophy of astrocytes when injected intracerebrally[66]. In the deafferented rat dentate gyrus, IL1 immunoreactive
Concluding remarks
Microglial cells are the resident macrophages of the CNS and thus form the interface between the neural parenchyme and the immune system. Although little is known about microglia in the normal CNS, it is obvious that they are quickly activated in all acute pathological events which might effect the CNS. Activation occurs within hours of a lesion and reveals a phenotypical repertoire. MHC class-I and -II, amyloid precursor proteins, IL1, IL2, IL6, TGF-β1, CREB, the complement components and
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