Microglia exit the CNS in spinal root avulsion

Area of Science:

• Neuroimmunology
• Cell Biology
• Spinal Cord Injury Research

Background:

• Microglia are the primary immune cells residing within the central nervous system (CNS).
• The capacity of microglia to migrate beyond the CNS boundaries has remained largely unexplored.
• Understanding microglial migration is crucial for comprehending neuroinflammatory and neurodegenerative processes.

Purpose of the Study:

• To investigate the migratory behavior of microglia outside the CNS in a relevant injury model.
• To identify the mechanisms governing microglial emigration and potential re-entry into the CNS.
• To characterize the functional state of microglia following peripheral nervous system (PNS) experience.

Main Methods:

• Utilized time-lapse imaging in an obstetrical brachial plexus injury (OBPI) model.
• Observed cellular responses of microglia and macrophages to injury.
• Analyzed microglial migration pathways and interactions with other cell types.

Main Results:

• Demonstrated that microglia can emigrate from the CNS to peripheral spinal roots.
• Identified microglia as the primary debris-clearing cells in this peripheral migration.
• Showed that peripheral-experienced microglia can re-enter the CNS and travel to distal sites, including the brain, carrying debris.
• Discovered emigration is N-methyl-D-aspartate receptor (NMDA)-dependent, while repulsion from macrophages restricts migration.

Conclusions:

• Microglia possess the ability to migrate outside the CNS, challenging traditional definitions of their territory.
• Peripheral migration and subsequent re-entry may play a role in the spread of cellular material and inflammation in disease states.
• This migratory capacity suggests novel therapeutic targets for CNS disorders involving microglial activation and movement.