Activated microglial cells migrate towards sites of excitotoxic neuronal injury inside organotypic hippocampal slice cultures

Heppner, Frank L.; Skutella, Thomas; Hailer, Nils P.; Haas, Dorit; Nitsch, Robert

doi:10.1016/s0165-5728(98)91346-7

Cited by 21 publications

(31 citation statements)

References 17 publications

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“…In particular, microglia can respond rapidly by migration to a site of injury or inflammation, where many of these stimuli accumulate. This was clearly illustrated by Heppner et al [24] , who introduced cultured microglia onto rodent organotypic hippocampal slices with NMDAinduced lesions, and demonstrated that microglial cells migrated to the site of a lesion and clustered around damaged neurons in the dentate gyrus and cornu ammonis.…”

Section: Factors Regulating Microglial Motilitymentioning

confidence: 90%

“…We now know that isolated microglial culture systems usually result in the activation of these cells characterised by amoeboid morphology, increased expression of adhesion molecules and production of large amounts of free radicals [23,24]. However, the deactivation and accompanying ramification of microglia are precipitated by interactions within the CNS microenvironment, and notably with astrocytes in vitro [25][26][27].…”

Section: /Malementioning

confidence: 99%

“…Microglia have been shown to respond by chemotaxis and migration to a variety of chemoattractive stimuli in the brain [145,146]. These include ß-amyloid peptide [147][148][149][150], complement 5a [113,137,146], TGF-ß [113], NGF [151], LPS [152], neuronal platelet activating factor [153], leukemia inhibitory factor [154], epidermal growth factor [23,24,155], neuronal M-CSF [156], substance P [149], zymosan-activated serum [114] and chemokines: C10 [157], RANTES [158,159], the beta chemokines MIP-1·, MIP-1ß, MCP-1 [158,160], as well as IL-8, IP-10 [159] and neuronal fractalkine [161,162]. In particular, microglia can respond rapidly by migration to a site of injury or inflammation, where many of these stimuli accumulate.…”

Section: Factors Regulating Microglial Motilitymentioning

confidence: 99%

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Differentiation, Ramification and Distribution of Microglia within the Central Nervous System Examined

Rezaie

Male

2001

Neuroembryol Aging

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The central nervous system contains several populations of mononuclear phagocytes. Principal amongst these are the tissue-resident microglia. These cells are considered to derive from circulating blood progenitors that colonise the developing human nervous system in the second trimester of fetal life. They first appear as amoeboid forms and gradually differentiate to process-bearing ‘ramified’ forms with maturation. Signals driving this transformation are known to be partly derived from astrocytes in vitro, and amoeboid microglial cells progressively ramify when co-cultured with astrocytes, mirroring the ‘differentiation’ of microglia in situ during development. In the adult, microglia occupy distinct non-overlapping territories in their ramified conformations, and are capable of ‘dedifferentiating’ to their activated amoeboid morphological states in a number of pathological circumstances. This is in keeping with the capacity of these cells for a rapid response to inflammatory cues in the CNS. The interchangeable morphological continuum of these cells supports the view that microglia represent a single heterogeneous population of resident mononuclear phagocytes capable of marked plasticity. This review will discuss signals that drive the colonisation, differentiation and ramification of microglia, and examines hypothetical models for their spatial distribution in the adult nervous system.

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Section: Factors Regulating Microglial Motilitymentioning

confidence: 90%

Section: /Malementioning

confidence: 99%

Section: Factors Regulating Microglial Motilitymentioning

confidence: 99%

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Differentiation, Ramification and Distribution of Microglia within the Central Nervous System Examined

Rezaie

Male

2001

Neuroembryol Aging

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“…However, the drawback of microglia-enriched cultures is that microglial cells respond quickly to microenvironmental changes and become activated (Slepko and Levi, 1996;Hurley et al, 1999;Lee et al, 2002); hence, these cultures do not reproduce the behavior of microglial cells in situ. In contrast, organotypic cultures of slices from different regions of the adult and developing CNS on semiporous membranes in an air-liquid interface (Stoppini et al, 1991) have proven valuable to investigate the differentiation (Hailer et al, 1996(Hailer et al, , 1997 and the migratory behavior (Hailer et al, 1997;Heppner et al, 1998;Czapiga and Colton, 1999;Dailey and Waite, 1999;Stence et al, 2001;Grossmann et al, 2002;Petersen and Dailey, 2004;Kurpius et al, 2007) of microglia.…”

Section: Introductionmentioning

confidence: 99%

Migration and ramification of microglia in quail embryo retina organotypic cultures

Carrasco

Navascués

Cuadros

et al. 2011

Developmental Neurobiology

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Organotypic cultures of retina explants preserve the complex cellular microenvironment of the retina and have been used as a tool to assess the biological functions of some cell types. However, studies to date have shown that microglial cells activate quickly in response to the retina explantation. In this study, microglial cells migrated and ramified in quail embryo retina organotypic cultures (QEROCs) according to chronological patterns bearing a resemblance to those in the retina in situ, despite some differences in cell density and ramification degree. Retinal explants from quail embryos at 9 days of incubation (E9) proved to be the best in vitro system for reproducing a physiological-like behavior of microglial cells when cultured in Eagle's basal medium supplemented with horse serum. During the first week in vitro, microglial cells migrated tangentially in the vitreal part of QEROCs, and some began to migrate radially from 3 days in vitro (div) onward, ramifying in the inner and outer plexiform layers, thus mimicking microglia development in the retina in situ, although reaching a lower degree of ramification after 7 div. From 8 div onward, microglial cells rounded throughout the explant thickness simultaneously with the nonphysiological appearance of dead photoreceptors and round microglia in the outernuclear layer. Therefore, E9 QEROCs can be used during the first week in vitro as a model system for experimental studies of molecules putatively involved in microglial migration and ramification.

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“…Czapiga and Colton [9] reported the presence of round microglia in organotypic brain slices which ramified and developed highly branched processes after prolonged culturing. When purified enriched microglia were added to brain slices, these microglia migrated into the slices and highly ramified [10,11]. Recently, we [12] have shown for the first time that mainly ameboid microglia in slices become activated in the presence of GM-CSF and that microglia highly proliferate and migrate out of the brain slice.…”

Section: Introductionmentioning

confidence: 97%

Protein Kinase C and Phosphoinositol-3-Kinase Mediate Differentiation or Proliferation of Slice-Derived Rat Microglia

Zassler

Schermer²,

Humpel³

2003

Pharmacology

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Granulocyte-macrophage colony-stimulating factor plays an important role in the activation of microglia in the central nervous system. We have recently shown (see text) that granulocyte-macrophage colony-stimulating factor activates the proliferation and subsequent migration of microglia from organotypic cortex brain slices. The aim of this study was to investigate whether this activation is modulated by different putative intracellular pathway inhibitors. Our data show that the protein kinase C inhibitor staurosporine enhanced the proliferation as well as the differentiation of slice-derived microglia, while the phosphoinositol-3-kinase inhibitor LY294002 markedly suppressed the proliferative activity. In conclusion, proliferation, migration, as well as differentiation of rat microglia are highly regulated by intracellular signaling cascades.

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Activated microglial cells migrate towards sites of excitotoxic neuronal injury inside organotypic hippocampal slice cultures

Cited by 21 publications

References 17 publications

Differentiation, Ramification and Distribution of Microglia within the Central Nervous System Examined

Differentiation, Ramification and Distribution of Microglia within the Central Nervous System Examined

Migration and ramification of microglia in quail embryo retina organotypic cultures

Protein Kinase C and Phosphoinositol-3-Kinase Mediate Differentiation or Proliferation of Slice-Derived Rat Microglia

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