FOR THE FIRST time ever scientists have directly observed what happens inside the brain during a concussion.
The study was published in the journal Nature earlier this month.
Scientists know the basics of what happens to the brain during a concussion, but they are just beginning to understand the kind of long-lasting brain damage people can suffer.
The NFL got a lot of heat back in October because of the incredible number of concussions players suffer. Scientists have recently discovered these players, and really anyone who gets a severe concussion or multiple concussions, can face a lifetime of brain trouble that can lead to things like depression and dementia.
But the findings from this new study could help researchers develop treatment for concussions that stop and maybe even reverse this damage.
Seeing the brain
To directly observe how a concussion progresses in the brain, the researchers anaesthetised mice and surgically thinned their skull bones down to about 30 micrometers thick. The researchers then used the blunt end of a surgical tool to gently compress the thinned area, recreating a concussion.
In most cases they only applied gentle pressure until the bone caved slightly inward, but in one set of experiments they purposefully cracked the skull bone, recreating a severe brain injury.
The skulls were thin enough for the scientists to use a light laser scanning microscope to watch what happened inside the brain in both of these conditions, compared to the normal brain.
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The left image shows how the scientists compressed the skulls of the mice; the right image shows how they used a special microscope to examine the brain’s protective layer.
The mice brains were injected with dye so the researchers could see which cells were dead or injured and how that changed over time. The scientists began observing the damage five minutes after they compressed the mice’s skulls and recorded the changes over 12 hours.
What actually happens inside the brain during a concussion?
Most of the damage seems to happen to the brain’s protective membrane. In the image below you can see the difference between a normal mouse brain (left column) and a mouse brain with a concussion (right column).
Only 30 minutes after head trauma the scientists noticed the presence of reactive oxygen species — which cause cell death and DNA damage — in the protective membrane surrounding the brain.
Scientists already knew that environmental stress, like a blow to the head, causes a spike in these reactive oxygen species.
The scientists noticed holes had appeared in the innermost layer of brain’s protective membrane called the glia limitans. The holes developed because the reactive oxygen species killed the cells that make up the membrane.
The brain tries to repair these holes by sending a specific type of immune cell, called microglia, to the damaged area. If the cells are sick but still alive, the microglia extend along the membrane and band together to create a “honeycomb” kind of mesh (row B in the image) as a back-up layer of protection. You can see that in a normal brain the microglial cells are more concentrated.
But if the cells are already dead, the microglia form into a “jellyfish” blob (row C in the image above) and try to plug up the holes and recycle the dead cells. The scientists found the mice’s brains could maintain this back-up protection for about 12 hours.
“These reactions, which have never been seen before in living brains, help secure the barrier and prevent toxic substances from getting into the brain” from the general blood supply in the rest of the body, study researcher Dorian McGavern, of the National Institutes Of Health, said in a press release.
The immune cells called neutrophils are the first responders, and flood the area (row D of the image) of dead cells within an hour after the head injury.
The neutrophils are attracted to chemicals given off by injured cells. They travel through blood vessels to the injured cells and help repair the cells and clean up the dead ones. These chemicals also make the vessels of the brain leaky, causing fluid to flow out of them and into the spaces between the neurons. All this fluid accumulates and makes the brain tissue swell up, just like any other bump or bruise.
But this is a more serious problem in the brain because the brain is much more fragile than other organs and does not have as much room to expand and swell. It presses against the skull and can cause serious brain tissue damage. Further, during the first 30 minutes a concussion kills off cells called meningeal macrophages (row A in the image) that are designed to keep inflammation and swelling under control.
Here, you see the yellow neutrophil cells squeeze through blood vessels and enter the brain. It only takes about an hour:
The future of concussion treatment
Another major revelation from this study is that the skull bone of the mice was more porous than scientists thought. If true for humans as well, it could be possible for doctors to send medication directly into the brain and slow down the damage a concussion causes. As long as the molecules are small enough, they will naturally diffuse through the skull bone, down through the membrane layers, and could even reach actual brain tissue.
When the scientists applied glutathione — an antioxidant naturally found in our cells that fights reactive oxygen species — to the worn down skull bone of the injured mice, it reduced cell death in the concussed patch of brain by 67%. And even when they waited three hours after the injury to apply it, it still reduced cell death by 50%.
“This idea that we have a time window within which to work, potentially up to three hours, is exciting and may be clinically important,” McGavern said in a press release.
This has not been tested in humans, and humans have a thicker skull bone than mice (and you wouldn’t want to shave your skull down to make it thin either). More testing and research is needed before the scientists can determine if the same kind of treatment could be used in humans.
What it looks like inside a concussed brain
FOR THE FIRST time ever scientists have directly observed what happens inside the brain during a concussion.
The study was published in the journal Nature earlier this month.
Scientists know the basics of what happens to the brain during a concussion, but they are just beginning to understand the kind of long-lasting brain damage people can suffer.
The NFL got a lot of heat back in October because of the incredible number of concussions players suffer. Scientists have recently discovered these players, and really anyone who gets a severe concussion or multiple concussions, can face a lifetime of brain trouble that can lead to things like depression and dementia.
But the findings from this new study could help researchers develop treatment for concussions that stop and maybe even reverse this damage.
Seeing the brain
To directly observe how a concussion progresses in the brain, the researchers anaesthetised mice and surgically thinned their skull bones down to about 30 micrometers thick. The researchers then used the blunt end of a surgical tool to gently compress the thinned area, recreating a concussion.
In most cases they only applied gentle pressure until the bone caved slightly inward, but in one set of experiments they purposefully cracked the skull bone, recreating a severe brain injury.
The skulls were thin enough for the scientists to use a light laser scanning microscope to watch what happened inside the brain in both of these conditions, compared to the normal brain.
The left image shows how the scientists compressed the skulls of the mice; the right image shows how they used a special microscope to examine the brain’s protective layer.
The mice brains were injected with dye so the researchers could see which cells were dead or injured and how that changed over time. The scientists began observing the damage five minutes after they compressed the mice’s skulls and recorded the changes over 12 hours.
What actually happens inside the brain during a concussion?
Most of the damage seems to happen to the brain’s protective membrane. In the image below you can see the difference between a normal mouse brain (left column) and a mouse brain with a concussion (right column).
Only 30 minutes after head trauma the scientists noticed the presence of reactive oxygen species — which cause cell death and DNA damage — in the protective membrane surrounding the brain.
Scientists already knew that environmental stress, like a blow to the head, causes a spike in these reactive oxygen species.
The scientists noticed holes had appeared in the innermost layer of brain’s protective membrane called the glia limitans. The holes developed because the reactive oxygen species killed the cells that make up the membrane.
The brain tries to repair these holes by sending a specific type of immune cell, called microglia, to the damaged area. If the cells are sick but still alive, the microglia extend along the membrane and band together to create a “honeycomb” kind of mesh (row B in the image) as a back-up layer of protection. You can see that in a normal brain the microglial cells are more concentrated.
But if the cells are already dead, the microglia form into a “jellyfish” blob (row C in the image above) and try to plug up the holes and recycle the dead cells. The scientists found the mice’s brains could maintain this back-up protection for about 12 hours.
The immune cells called neutrophils are the first responders, and flood the area (row D of the image) of dead cells within an hour after the head injury.
The neutrophils are attracted to chemicals given off by injured cells. They travel through blood vessels to the injured cells and help repair the cells and clean up the dead ones. These chemicals also make the vessels of the brain leaky, causing fluid to flow out of them and into the spaces between the neurons. All this fluid accumulates and makes the brain tissue swell up, just like any other bump or bruise.
But this is a more serious problem in the brain because the brain is much more fragile than other organs and does not have as much room to expand and swell. It presses against the skull and can cause serious brain tissue damage. Further, during the first 30 minutes a concussion kills off cells called meningeal macrophages (row A in the image) that are designed to keep inflammation and swelling under control.
Here, you see the yellow neutrophil cells squeeze through blood vessels and enter the brain. It only takes about an hour:
The future of concussion treatment
Another major revelation from this study is that the skull bone of the mice was more porous than scientists thought. If true for humans as well, it could be possible for doctors to send medication directly into the brain and slow down the damage a concussion causes. As long as the molecules are small enough, they will naturally diffuse through the skull bone, down through the membrane layers, and could even reach actual brain tissue.
When the scientists applied glutathione — an antioxidant naturally found in our cells that fights reactive oxygen species — to the worn down skull bone of the injured mice, it reduced cell death in the concussed patch of brain by 67%. And even when they waited three hours after the injury to apply it, it still reduced cell death by 50%.
“This idea that we have a time window within which to work, potentially up to three hours, is exciting and may be clinically important,” McGavern said in a press release.
This has not been tested in humans, and humans have a thicker skull bone than mice (and you wouldn’t want to shave your skull down to make it thin either). More testing and research is needed before the scientists can determine if the same kind of treatment could be used in humans.
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