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Published in: Journal of Neuroinflammation 1/2005

Open Access 01-12-2005 | Research

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

Authors: W Shawn Carbonell, Shin-Ichi Murase, Alan F Horwitz, James W Mandell

Published in: Journal of Neuroinflammation | Issue 1/2005

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Abstract

Background

Subventricular 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.

Methods

We 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.

Results

We 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.

Conclusions

Subependymal 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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Metadata
Title
Infiltrative microgliosis: activation and long-distance migration of subependymal microglia following periventricular insults
Authors
W Shawn Carbonell
Shin-Ichi Murase
Alan F Horwitz
James W Mandell
Publication date
01-12-2005
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2005
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/1742-2094-2-5

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