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Infiltrative microgliosis: activation and long-distance migration of subependymal microglia following periventricular insults

Authors
  • Carbonell, W Shawn1, 2
  • Murase, Shin-Ichi3
  • Horwitz, Alan F2, 3
  • Mandell, James W2, 4
  • 1 University of Virginia, Medical Scientist Training Program, Charlottesville, Virginia, 22908, USA , Charlottesville
  • 2 University of Virginia, Neuroscience Graduate Program, Charlottesville, Virginia, 22908, USA , Charlottesville
  • 3 University of Virginia, Department of Cell Biology, Charlottesville, Virginia, 22908, USA , Charlottesville
  • 4 University of Virginia, Department of Pathology (Division of Neuropathology), Charlottesville, Virginia, 22908, USA , Charlottesville
Type
Published Article
Journal
Journal of Neuroinflammation
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Jan 28, 2005
Volume
2
Issue
1
Identifiers
DOI: 10.1186/1742-2094-2-5
Source
Springer Nature
Keywords
License
Yellow

Abstract

BackgroundSubventricular microglia (SVMs) are positioned at the interface of the cerebrospinal fluid and brain parenchyma and may play a role in periventricular inflammatory reactions. However, SVMs have not been previously investigated in detail due to the lack of a specific methodology for their study exclusive of deeper parenchymal microglia.MethodsWe have developed and characterized a novel model for the investigation of subventricular microglial reactions in mice using intracerebroventricular (ICV) injection of high-dose rhodamine dyes. Dynamic studies using timelapse confocal microscopy in situ complemented the histopathological analysis.ResultsWe demonstrate that high-dose ICV rhodamine dye injection resulted in selective uptake by the ependyma and ependymal death within hours. Phagocytosis of ependymal debris by activated SVMs was evident by 1d as demonstrated by the appearance of rhodamine-positive SVMs. In the absence of further manipulation, labelled SVMs remained in the subventricular space. However, these cells exhibited the ability to migrate several hundred microns into the parenchyma towards a deafferentation injury of the hippocampus. This "infiltrative microgliosis" was verified in situ using timelapse confocal microscopy. Finally, supporting the disease relevance of this event, the triad of ependymal cell death, SVM activation, and infiltrative microgliosis was recapitulated by a single ICV injection of HIV-1 tat protein.ConclusionsSubependymal microglia exhibit robust activation and migration in periventricular inflammatory responses. Further study of this population of microglia may provide insight into neurological diseases with tendencies to involve the ventricular system and periventricular tissues.

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