Head injuries can disrupt the entire brain network in mice, important new maps reveal

Head injuries can disrupt the entire brain network in mice, important new maps reveal

We know that the brain changes after traumatic injury, and now we have maps from mice that show what that change looks like.

A team of researchers has tracked connections between nerve cells throughout the brain of mice, which shows that distant parts of the brain are disconnected after a head injury.

The amazing visualizations of connectivity throughout the brain can help researchers understand how a traumatic brain injury, or TBI, changes the intersection between different cells and brain regions, first in mice and then in humans.

“We have long known that communication between different brain cells can change very dramatically after an injury.” says neuroscientist and study author Robert Hunt of the University of California, Irvine (UCI), who envisioned the project a decade ago.

“But we have not been able to see what is happening in the whole brain until now.”

There is still so much that we do not fully understand traumatic brain injurywhich can leave people with lifelong disabilities, feeling like shadows of their former selves and almost unrecognizable to the family.

A TBI occurs when a blow to the head – often from a fall, car accident, sports collision or physical assault – sends the brain to ricochet around inside the skull, causing permanent damage.

Repeated head trauma leading to a serious condition called chronic traumatic encephalopathy has been well documented in professional athletes. But even “mild” headaches called concussions can obvious damage years latershows new research.

No two head injuries are usually the same, which makes them challenging to study, although there are common symptoms: memory problems, communication difficulties, lack of attention, Depressionand emotional instability, to name a few.

However, linking behavioral, emotional, and brain function changes to changes in specific brain cells or broader neural networks is one of the important tasks, as researchers hope to better understand how brain damage develops and whether its occurrence could be prevented.

In this study, Hunt and the team, led by fellow neuroscientist and UCI researcher Jan Frankowski, have developed some new and improved techniques for mapping nerve cell connections across the brain in a mouse model that replicates TBI using a dazzling set of laser-illuminated fluorescent tags.

Of particular interest was a group of neurons called somatostatin interneurons that control the input and output of local brain circuits and are among the most vulnerable to cell death after brain damage.

The trick was to infuse whole mouse brains with chemicals to make the completely intact, jelly-like organs transparent and image them before cutting the tissue into thin sections for further inspection under a microscope.

What the researchers saw was striking. Two months after an injury to the hippocampus, a brain region involved in learning and memory, neural circuits in the mice’s brains had been reconfigured.

Brain changes after injuryStained tissue sections of an undamaged and damaged brain region (Frankowski et al., Nat Commun., 2022)

Surviving somatostatin interneurons in the hippocampus became “hyper-connected hubs”, rich in nearby connections but disconnected from long-distance inputs; the same connection changes were also seen in distant parts of the brain, not directly damaged.

“It looks like the whole brain is being carefully switched on to cope with the damage, whether it was direct damage to the region or not.” explaining Alexa Tierno, PhD student in neuroscience at UCI and co-author of the study.

“But different parts of the brain probably don’t work as well together as they did before the injury.”

In their image exploration, the team also found evidence that the machines used by brain cells to establish distant connections remained intact after a serious injury. This bodes well for recovery because, says Hunt, it suggests that there may be a way to entice the damaged brain to repair lost connections on its own.

Based on previous workThe researchers grafted new neurons into the animals’ brains, at the site of the injury, and found that newly transplanted cells could be intertwined with existing, damaged circuits and receive input from the entire brain.

“Some people are free [brain cell] transplantation can rejuvenate the brain by releasing unknown substances to increase innate regenerative capacity. ” says Hunt. “But we are discovering that the new neurons are really plugged into the brain.”

However, this is not the only approach. Other research is considering the possibility that strengthening existing connections through learning can help restore brain function after injury, and so could encourage new brain cells to growa process that slows down with age.

With cell-based therapies still far away, the researchers behind this latest study say their next step will be to look at what can happen to other cell types (they only studied one) and in other brain areas after injury.

Investigating whether the brain-wide circulatory changes observed in mice are also evident in people who have experienced traumatic brain injury, and whether they may contribute to disability and epilepsy, will be another real test in the future.

“Understanding the types of plasticity that exist after an injury will help us rebuild the damaged brain with a very high degree of precision.” says Hunt. “However, it is very important that we step towards this goal, and it takes time.”

The study was published in Nature communication.


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