The International Journal of Biochemistry & Cell Biology
Cells in focusMicroglia: Activation in acute and chronic inflammatory states and in response to cardiovascular dysfunction
Introduction
Microglia are the brain's resident immune cells involved in the surveillance of the microenvironment. Microglia are abundant within the brain and comprise up to approximately 20% of the total glial population. They are found in both the gray and white matter but are not uniformly distributed, and their density can vary considerably between brain regions. The greatest concentrations are found in areas that include the hippocampus, basal ganglia, and substantia nigra. The lowest density of microglia is found in areas that include the brainstem and cerebellum (Savchenko et al., 1997).
Microglia were first observed by Nissl staining and were subsequently characterized as glial cells by Ramon y Cajal. It was Ramon y Cajal's student, Rio-Hortega, who focussed on microglia and identified them as a separate cell population, distinct from the other glial cells, and capable of phagocytosis. From his work he correctly hypothesised microglia were derived from myeloid mononuclear cells.
At rest in the adult brain, microglia have a small soma with little perinuclear cytoplasm. Arising from the soma are several main processes from which emanate numerous extensively branched fine processes that are long thin and finger-like, a morphology termed ramified (Fig. 1). The processes of microglia can contact astrocytes, neurons and blood vessels but do not appear to contact other microglia, and there can be 50–60 μm between individual microglia. Recent work using time lapse photography combined with two-photon microscopy has shown that microglia at ‘rest’ are in fact highly motile with their fine processes undergoing cycles of retractions and elongations that suggests sampling of the microenvironment (Nimmerjahn et al., 2005, Lambertsen et al., 2009, Wake et al., 2009). Calculations of the speed of the motility of the processes and the volume of extracellular space in the brain suggest that the brain parenchyma can be completely sampled in a few hours (Nimmerjahn et al., 2005). Microglia are kept in this ‘resting’ state by ‘stimulatory’ and ‘inhibitory’ signals finely balanced in the microenvironment.
Upon an insult to the brain tissue, such as an injury, or ischemia, microglia become activated, markedly changing their morphology and this is reviewed in detail by several recent reviews (Colton and Wilcock, 2010, von Bernhardi et al., 2010). The changes include an enlarged soma and thicker, shorter processes that have a stubby appearance (Fig. 1). Some activated microglia become ameboid, capable of phagocytosing debris and proliferation (Fig. 1).
Section snippets
Cell origin and plasticity
Microglia retain the ability to divide, and to undergo DNA synthesis so that they can maintain the population of microglia in the central nervous system without reliance on peripheral, bone marrow haematopoietic cell production. Microglia are derived from haematopoietic progenitor cells but the exact lineage and derivation of microglia is not known. Unlike astrocytes, oligodendrocytes and neurons which are derived from the neuroectoderm, microglia are believed to derive from peripheral myeloid
Functions
The fundamental functions of the microglia involve protecting the central nervous system by detecting and acting upon invading organisms, injury or other insults. As discussed earlier, in normal conditions, microglia are believed to constantly survey their environment using their motile fine finger-like processes. When there is an insult, infection, injury to the tissue, or stimulatory signals are present in the microenvironment the microglia become activated and can undergo phenotypic and
Associated pathologies
Activation of microglia has been observed in many conditions of chronic inflammation within the central nervous system. Below I briefly discuss Alzheimer's and Parkinson's diseases and neuropathic pain. Before doing so, we discuss the potential roles of microglia in cardiovascular conditions, firstly in a condition in which there is an initial acute injury or insult to the brain (i.e. stroke/cerebral ischemia) and secondly, a cardiovascular condition in which there is no direct injury to the
Conclusion
Microglia are the resident immune cells in the central nervous system and are constantly monitoring their environment. At the first signs of an insult or injury to the tissue, they become activated and secrete both pro- and anti-inflammatory mediators. Thus they can have both detrimental and protective actions. Microglia are activated in many conditions that involve chronic inflammation such as Alzheimer's and Parkinson's diseases and in neuropathic pain. Following cerebral ischemia and stroke,
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