Scientists identify immune cells that remove degenerating neurons after brain injury

Researchers from the University of Virginia School of Medicine have identified the immune cells that are responsible for clearing dead and dying nerve cells following brain injury.

Microglia (red) gradually clear away the neuronal debris (green) produced following damage to the optic nerve. Norris et al., 2018.

As reported in the Journal of Experimental Medicine, Jonathan Kipnis and colleagues found that specialized immune cells called microglia play a key role in clearing the dead material by gobbling up the remnants of injured neurons. This stops the damage from spreading to nearby neurons and causing further neurodegeneration.

In all bodily tissues, dead or dying cells are quickly removed to stop inflammation setting in, which can cause neighboring cells to die.

Scientists already knew that specialized cells called phagocytic cells carry this out by engulfing and breaking down cellular debris. However, it was not known which cells are responsible for this when the brain or spinal cord is damaged.

Now, Kipnis and colleagues have studied injuries to the optic nerve in mice that cause the degeneration of retinal ganglion neurons and leave debris in a distant region of the brain.

The team found that this debris is engulfed by microglia, phagocytic cells that reside in the central nervous system where they gobble up pathogens that have infected the brain.

These microglia are also important for brain development since they clear neuronal synapses that have failed to become fully active. In the adult brain, microglia seem to recognize damaged neurons using some of the same molecules they use to recognize pathogens or inactive synapses.

The study showed that once the optic nerve is injured, the microglia produce “complement” proteins that enable them to recognize their targets.

Kipnis and team then looked at what happens following optic nerve injury when the microglia do not produce these proteins and found that the microglia failed to clear the debris.

Knowing these mechanisms might allow us to boost the clearance of potentially toxic debris by microglia and limit the spread of neurodegeneration following brain or spinal cord injury."

Jonathan Kipnis, Lead Author

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