Finding Injury

The brain’s phagocytes follow an ATP bread trail laid down by calcium waves to the site of damage.

By | September 1, 2012

RIDING THE WAVE: Microglia (purple) responding to an injury-induced Ca2+ wave (gray) in zebrafish brain tissue surrounded by blood vessels (blue)EMBL Heidelberg, Dirk Sieger




The paper

D. Sieger et al., “Long-range Ca2+ waves transmit brain-damage signals to microglia,” Dev Cell, 22:1138-48, 2012.



The finding

When a brain injury occurs, microglia—phagocytic cells that reside in the central nervous system—flock to the site to clear injured neurons and allow tissue regeneration. Monitoring the process in vivo in the brains of zebrafish embryos, Francesca Peri at the European Molecular Biology Laboratory in Heidelberg, Germany, and colleagues observed that calcium waves are responsible for carrying the ATP signal that draws microglia to the injury site.



The cut

“How microglia rapidly recognize damaged cells located at a distance has remained elusive,” says neuroscientist Samuel David at McGill University, who was not involved in the study, in an e-mail. So Peri and colleagues used a laser cutting device mounted to a confocal spinning-disk microscope to inflict precise, reproducible damage to the brains of larval zebrafish and filmed how microglia, involved in brain healing, reacted.



The path

It was known that microglia follow extracellular ATP to the injury site, but ATP degrades rapidly in this situation, so it was unclear how it could travel across the brain to attract microglia if it diffused from a single point source. Peri’s team noticed that rapid waves of Ca2+ propagating from the injury site stimulated the release of ATP from healthy cells surrounding the injured tissue, drawing in the microglia. Real-time analysis suggested that injured cells released glutamate, which instigated the calcium wave.



The crowd

While essential, excess microglia can impair recovery and cause neuronal damage through inflammation. The mechanism for this is not precisely known, and Peri hopes that by inflicting cuts of different scales, some of the mystery may be uncovered.



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