Maps from mice show what the brain changes after a traumatic injury.
The connections between nerve cells in the entire brain of mice have been traced by a team of scientists.
The visualization of brain-wide connections could help scientists understand how a traumatic brain injury alters cross-talk between different cells in the brain.
"We've known for a long time that the communication between different brain cells can change very dramatically after an injury," says Robert Hunt, who conceived the project a decade ago.
We haven't been able to see what's happening in the brain.
There's still so much we don't know about traumatic brain injuries, which can leave people with lifelong disabilities, feeling like shadows of their former selves.
When a blow to the head causes brain damage, it's called a Traumatic Brain Injury.
Chronic traumatic encephalopathy is a serious condition that can be caused by repeated head traumas. Recent research shows that even mild head knocks can cause long term damage.
There are many symptoms of head injuries, including memory problems, communication difficulties, attention deficits, depression, and emotional instability, so it's difficult to study them.
Researchers hope to better understand how brain damage develops and if it can be prevented by linking behavioral, emotional, and brain function changes to changes in specific brain cells or wider neural networks.
Hunt and the team devised a few new and improved techniques to map connections between nerve cells across the entire brain in a mouse model replicating traumatic brain injury using a dazzling array of laser-illuminated fluorescent tags.
By that time, iDISCO was well established and we modified the clearing protocols to achieve strong immunoslabeling throughout an entire injured brain, without separating the brains into two hemispheres as is commonly done pic.twitter.com/5qborRCuNN
— robert hunt 🔥 (@hunt_lab) June 14, 2022
The somatostatin interneurons, which control the input and output of local brain circuits, are one of the most vulnerable to cell death following brain injury.
The trick was to inject whole mouse brains with chemicals to make them transparent and then to slice the tissue into thin sections for further examination.
The researchers saw something that struck them. Two months after an injury to the hippocampus, neural circuits in the mice brains had rearranged themselves.
There are stained tissue sections of the brain region.
Surviving somatostatin interneurons in the hippocampus became 'hyper connected hubs', rich with close-range connections but disconnected from long-range inputs.
"It looks like the entire brain is being carefully rewired to accommodate for the damage, regardless of whether there was direct injury to the region or not," says the co-first author of the study.
Different parts of the brain are not working as well as they used to.
The team discovered that the machinery brain cells use to establish distant connections remained intact after a serious injury. Hunt says that it suggests that the injured brain may be able to repair itself on its own.
The new cells were able to connect with existing circuits and receive input from all over the brain.
So, we transplanted SST interneurons into brain injured hippocampus and mapped their connections. The new SST interneurons received appropriate connections from all over the brain, providing a potential circuit basis for interneuron cell therapy pic.twitter.com/MPATNJn6fv
— robert hunt 🔥 (@hunt_lab) June 14, 2022
Hunt says that some people have suggested that brain cell transplantation could boost the brain's innate regeneration capacity. The new cells are hard-wired into the brain.
It isn't the only approach. Brain function can be restored after an injury if existing connections are strengthened through learning and new brain cells are encouraged to grow.
With cell-based therapies still a long way off, the researchers behind this latest study say their next step will be to look at what might be happening with other cell types.
If the brain-wide circuit changes observed in mice can be seen in people who have experienced a traumatic brain injury, that will be another real test.
Hunt says that it will be possible to rebuild the injured brain with a high degree of precision by understanding the types of plasticity that exist after an injury. We need to proceed step-wise towards this goal, and that takes time.
The study was published in a scientific journal.
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