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How the Circadian Clock Helps the Brain Recover After Injury

A type of brain cell that can renew itself is regulated by circadian rhythms, providing significant insights into how the body’s internal clock may promote healing after traumatic brain injuries (TBI), according to new research from Children’s National Hospital.

In the United States alone, approximately 2.8 million people sustain TBI annually, including 630,000 children. TBI is the leading cause of death in people under age 45, and those who survive are often left with persistent physical, cognitive and psychological disabilities.

Yet no targeted therapies exist for TBI, creating a critical need to uncover the mechanisms that could unlock the regeneration of these NG2-glia cells, which are the most common type of brain cell known to proliferate and self-renew in adult brains.

“It is essential for researchers to know that cell renewal is coordinated with the time of day,” said Vittorio Gallo, Ph.D., interim chief academic officer and interim director of the Children’s National Research Institute. “With this knowledge, we can dig deeper into the body’s genetic healing process to understand how cells regulate and regenerate themselves.”

The molecular circadian clock can be found throughout the body and is essential for the synchronizing cellular physiology with the 24-hour day. However, the role of the clock in regulating the brain’s regenerative potential has not been explored.

We report here that murine NG2-glia, the largest population of proliferative cells in the mature central nervous system, rhythmically express circadian clock genes in a 24-hour period, including the critical clock component Bmal1 RNA and BMAL1 protein.

Interestingly, daily NG2-glia proliferation preferentially occurs during the time of day in which Bmal1 expression is high, while conditional knockout (CKO) of Bmal1 decreases both cortical NG2-glia density and cellular proliferation.

Furthermore, in a neurotrauma model, we show that pathology-induced NG2-glia proliferation is also dependent on Bmal1 expression.

Because circadian rhythm disturbances are common in neurologic disorders across the lifespan, including in TBI, these findings bear significant implications for cellular regeneration in brain injuries and disease.


NG2-glia, a newly discovered type of brain cell that can renew itself is regulated by circadian rhythms. The findings shed new light on how the body’s circadian clock can promote healing following a traumatic brain injury.

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