Trends in Neurosciences
Volume 19, Issue 8, August 1996, Pages 312-318
Journal home page for Trends in Neurosciences

Microglia: a sensor for pathological events in the CNS

https://doi.org/10.1016/0166-2236(96)10049-7Get rights and content

Abstract

The most characteristic feature of microglial cells is their rapid activation in response to even minor pathological changes in the CNS. Microglia activation is a key factor in the defence of the neural parenchyma against infectious diseases, inflammation, trauma, ischaemia, brain tumours and neurodegeneration. Microglia activation occurs as a graded response in vivo. The transformation of microglia into potentially cytotoxic cells is under strict control and occurs mainly in response to neuronal or terminal degeneration, or both. Activated microglia are mainly scavenger cells but also perform various other functions in tissue repair and neural regeneration. They form a network of immune alert resident macrophages with a capacity for immune surveillance and control. Activated microglia can destroy invading micro-organisms, remove potentially deleterious debris, promote tissue repair by secreting growth factors and thus facilitate the return to tissue homeostasis. An understanding of intercellular signalling pathways for microglia proliferation and activation could form a rational basis for targeted intervention on glial reactions to injuries in the CNS. Trends Neurosci. (1996) 19, 312–318

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

References (75)

  • V.H. Perry et al.

    Trends Neurosci.

    (1993)
  • J. Gehrmann et al.

    Brain Res. Rev.

    (1995)
  • E.R. Whittemore

    Brain Res.

    (1993)
  • M.B. Graeber

    Neurosci. Lett.

    (1988)
  • W.J. Streit et al.

    J. Neuroimmunol.

    (1989)
  • M. Buttini

    Neuroscience

    (1996)
  • M. Svensson et al.

    Exp. Neurol.

    (1993)
  • D.T. Theodosis et al.

    Trends Neurosci.

    (1996)
  • C. Kaltschmidt

    J. Neuroimmunol.

    (1994)
  • C.A. Colton et al.

    FEBS Lett.

    (1987)
  • S.C. Lee

    J. Neuroimmunol.

    (1993)
  • K. Nakajima

    Brain Res.

    (1992)
  • K. Nakajima

    FEBS Lett.

    (1992)
  • H. Wekerle

    Trends Neurosci.

    (1986)
  • J. Maehlen

    J. Neuroimmunol.

    (1989)
  • J. Gehrmann et al.

    J. Neuroimmunol.

    (1993)
  • A.M. Fagan et al.

    Exp. Neurol.

    (1990)
  • J. Bauer

    J. Neuroimmunol.

    (1993)
  • A.M. Van Dam

    Neuroscience

    (1995)
  • M.N. Woodroofe

    J. Neuroimmunol.

    (1991)
  • Del-Rio Hortega, P. (1932) in Cytology and Cellular Pathology of the Nervous System (Penfield, W., ed.), pp. 481–534,...
  • E.A. Ling et al.

    Glia

    (1993)
  • W.F. Hickey et al.

    J. Neuropathol. Exp. Neurol.

    (1992)
  • Fedoroff, S. (1995) in Neuroglia (Kettenmann, H. and Ransom, B.R., eds), pp. 162–181, Oxford University...
  • W.J. Streit et al.

    Glia

    (1988)
  • D.W. Dickson

    Lab. Invest.

    (1991)
  • D. Giulian

    J. Neurosci.

    (1989)
  • P.L. McGeer

    Acta Neuropathol.

    (1988)
  • J. Gehrmann

    Brain Pathol.

    (1993)
  • H. Kettenmann

    J. Neurosci. Res.

    (1990)
  • H. Kettenmann et al.

    Glia

    (1993)
  • W. Walz

    J. Neuroscience

    (1993)
  • J.M. Langosch

    Br. J. Pharmacol.

    (1994)
  • J. Priller

    Glia

    (1995)
  • Jakob, A. (1927) in Handbuch der Psychiatrie 1 (Aschaffenburg, G., ed.), p. 268,...
  • Merzbacher, L. (1909) Untersuchungen über die Morphologie und Biologie der Abräumzellen im Zentralnervensystem, Fischer...
  • F. Nissl

    Arch. Psych.

    (1899)
  • Cited by (3836)

    View all citing articles on Scopus
    View full text