Microglia exit the CNS in spinal root avulsion

• Published in: PLoS biology Vol. 17; no. 2; p. e3000159
• Main Authors: Green, Lauren A, Nebiolo, Julia C, Smith, Cody J
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 22.02.2019; Public Library of Science (PLoS)
• Subjects: Animals; Animals, Genetically Modified; Autism; Biology and Life Sciences; Brachial Plexus - injuries; Brachial Plexus - metabolism; Brain; Brain injury; Cell Communication; Cell migration; Cell Movement; Central nervous system; Debris; Dependence; Disease; Embryo, Nonmammalian; Emigration; Gene Expression; Genes, Reporter; Glutamic acid receptors (ionotropic); Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Humans; Lasers; Macrophages; Macrophages - metabolism; Macrophages - pathology; Medicine and Health Sciences; Microglia; Microglia - metabolism; Microglia - pathology; Models, Biological; Morphogenesis; N-Methyl-D-aspartic acid receptors; Nervous system; Neuroimaging; Pain; Peripheral nervous system; Physical Sciences; Receptors, N-Methyl-D-Aspartate - genetics; Receptors, N-Methyl-D-Aspartate - metabolism; Research and Analysis Methods; Short Reports; Spinal cord; Spinal Cord - metabolism; Spinal Cord - pathology; Spinal cord injuries; Spinal Cord Injuries - genetics; Spinal Cord Injuries - metabolism; Spinal Cord Injuries - pathology; Spinal Nerve Roots - injuries; Spinal Nerve Roots - metabolism; Stem cells; Time-Lapse Imaging; Zebrafish; Indiana; United States > US
• ISSN: 1545-7885; 1544-9173; 1545-7885
• DOI: 10.1371/journal.pbio.3000159

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.