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.
Highlights
Microglia are the surveying phagocytic cells of the central nervous system (CNS) [1,2,3]
We show that CNS-resident microglia exit their domain to clear peripheral nervous system (PNS) debris in these injuries
We show that the exit of microglia to the PNS is mediated by opposing mechanisms; N-methyl-D-aspartate (NMDA) receptor and glutamate induce emigration, whereas contact-dependent repulsion prevents intrusion
Summary
Microglia are the surveying phagocytic cells of the central nervous system (CNS) [1,2,3]. They enter the CNS during embryonic development [4,5]. Microglia emigrate after avulsion decision to publish, or preparation of the manuscript
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