Microglia exit the CNS in spinal root avulsion

Lauren A Green; Julia C Nebiolo; Cody J Smith

doi:10.1371/journal.pbio.3000159

Microglia exit the CNS in spinal root avulsion

PLoS Biol. 2019 Feb 22;17(2):e3000159. doi: 10.1371/journal.pbio.3000159. eCollection 2019 Feb.

Authors

Lauren A Green^{1

2}, Julia C Nebiolo¹, Cody J Smith^{1

2}

Affiliations

¹ Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana, United States of America.
² Center for Stem Cells and Regenerative Medicine, University of Notre Dame, Notre Dame, Indiana, United States of America.

Abstract

Microglia are central nervous system (CNS)-resident cells. Their ability to migrate outside of the CNS, however, is not understood. Using time-lapse imaging in an obstetrical brachial plexus injury (OBPI) model, we show that microglia squeeze through the spinal boundary and emigrate to peripheral spinal roots. Although both macrophages and microglia respond, microglia are the debris-clearing cell. Once outside the CNS, microglia re-enter the spinal cord in an altered state. These peripheral nervous system (PNS)-experienced microglia can travel to distal CNS areas from the injury site, including the brain, with debris. This emigration is balanced by two mechanisms-induced emigration via N-methyl-D-aspartate receptor (NMDA) dependence and restriction via contact-dependent cellular repulsion with macrophages. These discoveries open the possibility that microglia can migrate outside of their textbook-defined regions in disease states.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Animals, Genetically Modified
Brachial Plexus / injuries
Brachial Plexus / metabolism
Cell Communication
Cell Movement
Embryo, Nonmammalian
Gene Expression
Genes, Reporter
Green Fluorescent Proteins / genetics
Green Fluorescent Proteins / metabolism
Humans
Macrophages / metabolism*
Macrophages / pathology
Microglia / metabolism*
Microglia / pathology
Models, Biological
Receptors, N-Methyl-D-Aspartate / genetics
Receptors, N-Methyl-D-Aspartate / metabolism*
Spinal Cord / metabolism
Spinal Cord / pathology
Spinal Cord Injuries / genetics
Spinal Cord Injuries / metabolism*
Spinal Cord Injuries / pathology
Spinal Nerve Roots / injuries
Spinal Nerve Roots / metabolism*
Time-Lapse Imaging
Zebrafish

Substances

Receptors, N-Methyl-D-Aspartate
Green Fluorescent Proteins

Grants and funding

This work was supported by the University of Notre Dame, the Elizabeth and Michael Gallagher Family, the Alfred P. Sloan Foundation (FG-2017-9531), Center for Zebrafish Research at the University of Notre and Center of Stem Cells and Regenerative Medicine at the University of Notre Dame and the Indiana State Board of Health (IDOH) Traumatic Brain and Spinal Cord Injury Research Fund. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.