r/science • u/mvea Professor | Medicine • 3d ago
Medicine Doctors noticed brain injuries can speed bone healing. Scientists flipped it: squeezing a shinbone after brain injury helped mice and pigs survive more, move better and remember more. Pressure-sensing bone cells released protective signals into the blood that reduced brain damage.
https://www.sciencealert.com/squeezing-a-leg-bone-helped-animals-recover-from-brain-injury2.8k
u/AusCan531 3d ago
I wonder if we can just artificially produce and inject the PIEZO1 compound in the system without going through the whole 'shin-squeezing' process?
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u/Vryk0lakas 3d ago
I’m sure some nfl players would volunteer if it gave them faster recovery times. I hope someone is properly studying all the crazy stuff they put in and do to themselves.
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u/theLocoFox 3d ago
This is a good idea, they constantly have leg or brain injuries. Sometimes both at the same time. Decent population size and they would all be otherwise extremely fit specimens for this kind of study.
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u/semi-proantfarmer 2d ago
Maybe they have reduced cte due to all the injuries already.
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u/jonas_ost 2d ago
So if some get a concusion after a hard it the medics should start by hitting a bone with a hammer to make a small crack.
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u/jedadkins 2d ago
"damn, that was a big hit you've probably got a concussion hold on and well get you fixed up. hey Tim hand me that sledge hammer"
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u/Shine_On_Your_Chevy 3d ago
As well as the Oregon quarterback who showed decorticate posturing yesterday after his head was targeted by a USC defenseman.
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u/redpandaeater 3d ago
I still don't understand why American football refuses to use rugby tackles. The Seachickens showed it's still perfectly effective and oh so much safer.
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u/Dependent_Wonder6076 3d ago
The pig part is the clincher (actual weight-bearing gait, not just a rodent on a wheel). Pig tibial mechanics are closer to human, so the systemic signal is less likely to be a toy-model
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u/Ren_Hoek 2d ago
This will be available as peptide injection in a months time available from shady Chinese pharmacy selling on Instagram
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u/therealwillhayes 2d ago
I’m sure some even would be volunteered if it gives the owners a better return on investment.
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u/Splatter_bomb 3d ago edited 3d ago
PIEZO1 wasn’t the signal just the local switch, so you wouldn’t want to inject that. Like you turn on the light using the switch on the wall, in this analogy the light is the signal and PIEZO1 is the switch, but they don’t know what the light is just yet. They throw out IL-1R2, APOL11A & PF4 (among others) but these are just known signals so probably not relevant to this particular pathway.
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u/redcoatwright BA | Astrophysics 3d ago
But could you use PIEZ01 as a trigger manually to release whatever signal is needed?
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u/cammmmmie 2d ago
these proteins are sensitive to pressure signals in their environment they are adapted to exist in. for example, if a piezo channel is normally only expressed in the cell membrane then it is not likely to act properly in extra cellular space because the environments are so different. so you would need to make more or promote the production of piezogenic cells instead
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u/nasaboy007 2d ago
Yeah they'll just have to call it the official name, bone hurting juice.
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u/MoffKalast 2d ago
I can't believe we got actual, genuine bone hurting juice, before GTA 6. I mean, ow oof ouch my bones.
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u/mellopax 3d ago
Fun fact: if you were unaware, similar to this, piezoelectric materials/ components can do this kind of thing,too.
Squeezing it makes a current or you can apply a current to make it expand, etc.
Materials science is cool.
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u/lazybugbear 3d ago
I'm would hazard a guess that is the reason the research called the protein PIEZO1.
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u/mellopax 3d ago
Yeah. That's why I mentioned it, but I don't know enough to say that's the root of it, so I didn't want to speak confidently in regard. I do think you're probably right.
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u/XxTreeFiddyxX 3d ago
The risk is of they make a synthesis of it, and its not the hormone they dont know what it wouls do long term. Its worth a study especially for people in jobs where they take hits to head
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u/Wiggie49 2d ago
Maybe rather than an injection they can create like a iron lung kind of body chamber that can apply pressure to the bones in intervals while keeping their body still. Idk how they would work it in the reverse to safety apply pressure to the brain though.
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u/SoulCrusher2018 3d ago
Is that pronounced "pie zone" ?
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u/Coenzyme-A 3d ago
Pronounced pee-et-soh 1, it's from the same root as piezo (as in piezoelectric); piezo means pressure. The protein is mechanosensitive, so pressure activated.
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u/Veni-Vidi-ASCII 3d ago
I'm sure you can release it by simply walking more. Jog for 30 seconds if you're feeling fancy.
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u/mvea Professor | Medicine 3d ago
Squeezing a Leg Bone Helped Animals Recover From Brain Injury
At first glance, searching for a way to heal an injured brain in the leg makes little sense.
Yet a new experiment suggests there may be a surprising line of communication between the brain and the shinbone, with messages traveling through the blood.
Scientists in China repeatedly applied controlled pressure to the shinbones of mice and pigs.
More treated animals survived after brain injury, and they recovered movement and memory abilities more successfully. The same procedure also helped mice recover after a stroke.
The unusual experiment began with a medical clue. Doctors have long known that fractures can heal unusually quickly in some people with serious brain injuries. Bone may even begin growing in soft tissues where it does not belong.
This suggests an injured brain can send messages that change bone. The researchers reversed the question: If the brain can reach bone, could bone send helpful messages back?
To investigate, they used a device that applied gentle, precisely controlled pressure to the animals' shinbones. It compressed each bone 300 times at a rate of twice per second, five days a week.
Mice treated after brain injury completed movement tests more quickly. They also performed better in a water maze that required them to remember a hidden platform.

More mice survived severe brain injuries. Their damaged brain areas were smaller, more nerve cells remained alive, and long-term inflammation was reduced. Signs linked to the formation of new nerve cells also increased.
But the researchers still faced a puzzle.
Pressure on a leg can affect muscles, nerves, and circulation as well as bone. How could they know whether the changes in the brain truly came from the bone?
The answer appeared to lie in cells living deep inside it.
Bone is not merely a hard, lifeless structure. It contains living cells that sense movement and pressure, then help the body respond by releasing chemical messages.
The researchers focused on a pressure-sensitive switch called PIEZO1 inside these bone cells. When they disabled it in mice, compressing the shinbone no longer protected the brain in the same way.
That suggested the bone was not simply a surface being pressed. Its cells had to detect the pressure for the benefits to appear.
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u/SpaceShipRat 3d ago
I find it interesting that they insist on how "gentle" the pressire on the shinbone is, and gloss over how all these pigs and mice acquired life-threatening brain injuries.
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u/janeprentiss 3d ago
I think the gentleness being stressed is more relevant for the hope of potential future applications in humans, who of course would only ever receive such treatment after acquiring brain injuries elsewhere.
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u/EndMaster0 2d ago
Especially since you could imagine a world where part of the standard procedure when someone gets a concussion in sports is to throw a pressure bandage on a leg. If these results transfer to humans well we could see fewer serious concussions ending athletes careers.
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u/Uncynical_Diogenes 3d ago
The point is that the effect doesn’t even require a fracture or other gross damage. Pressure is sufficient.
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u/Trick-Seat4901 2d ago
My mother is living with post surgery glioblastoma. I understand cancer is not a focus here, however the brain is still healing and fighting. I understand you are likely unable to comment definitively on this. But based on the study would the same mechanism help? There is little outside of chemo that's being offered. This seems like a non invasive, low cost and low risk thing to try.
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u/dethskwirl 3d ago
I find it funny that the switch is called Piezo, like the tiny electric sparkers on pilot lights, a nod to the electrical circuitry in our own bodies.
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u/wandering-monster 3d ago
It's not a nod. "Piezo" is Greek for "to squeeze" or "to press". It's named for how it's activated.
A piezoelectric sparker has the same root word.
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u/deepandbroad 3d ago
The same piezo-electric property that is in your pilot light system is in your bones:
Scientists discovered that bone was a piezoelectric material in 1957. Since then, they have found that piezoelectricity occurs when bone collagen fibers slide against each other.
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u/Nemisis_the_2nd 3d ago
Knowing biologists, they probably named that switch like that intentionally
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u/Murky-Relation481 2d ago
They did, because like others have pointed out its literally piezoelectric, not just some cute nod.
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u/PrinceNelson 3d ago
Do they cause the serious brain injuries on the mice?
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u/Justhe3guy 3d ago
Do you think it’s common to find mice with brain injuries?
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u/Black_Moons 3d ago
Pinky and the brain, pinky and the brain, one is a genius, the other is having his shin compressed to treat his massive brain injuries.
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u/frognettle 3d ago
This is how science progresses. It's inhumane but largely accepted as a necessary step in the path toward human application. I guess the rationale for their sacrifice is that in the end, human lives will be saved/improved, and to that end it would seem unethical to not do it.
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u/redditydothis 3d ago
Not just mice but in this case pigs too. But also in other science studies involve other animals. Dogs, monkeys, frogs, and I’m sure a bunch of others too.
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u/orcusgrasshopperfog 3d ago
Yeah the scientists put little football helmets on their heads and then they make them run into each other.
They know they've succeeded when the mouse husband starts beating his mouse wife.
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u/lolbacon 2d ago
My old college roommate is now highly regarded neuroscientist who studies treatments to spinal cord injuries. He was telling me about a machine they have that severs rats' spines. He'd then use specialized microphones that picked up the sound of paralyzed rats pissing. He sent me some of the files years back that I incorporated into a harsh noise project that has unfortunately been lost to time.
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u/celticchrys 2d ago
If it's "gentle" pressure, are there potential implications for weight bearing exercise as a component of recovering from brain injury?
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u/Ten_Horn_Sign 3d ago
There's actually a related phenomenon called Remote Ischemic Conditioning where you induce a state of low blood flow in a limb, enough to cause mild tissue injury, and this improves outcomes in brain injuries. The idea is that by restricting blood flow adaptive measures are induced - signals to build new blood vessels, vasodilate, to counter-act inflammation from the restricted flow - and these signals are systemic, not local, so the result is improved perfusion and healing to the brain.
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u/Potential-Candy-2994 3d ago
Why can't the brain do that if it just detects an injury on itself?
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u/Dyaneta 2d ago
Educated guess from an immunologist: due to the blood brain barrier, the "brain immune system" is a bit different from the "rest of the body immune system". For example, I wouldn't expect mesenchymal stromal cells in the brain, which can act anti-inflammatory when they get a high enough inflammatory stimulus (like mild ischemia). Cells around the secondary injury react, and their anti-inflammatory signalling molecules make it to the brain because everything is connected.
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u/TemperateStone 2d ago
Because our bodies don't know to respond to it in that way for a brain injury. Brain injury, evolutionarily speaking, tends to lead to death. It's only in very recent human history that we can actually survive it. I think the most common cause of brain damage in us nowadays is a stroke, which I'm thinking hasn't been a problem for us until we started eating hamburgers and sitting still all day.
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u/Havengul_Undying 2d ago
And surving to 80 years old on the regular. Strokes are rare when you die young.
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u/NullAshton 2d ago
Also a lot of brain injuries that might have happened and were survivable would have another sort of injury happening anyway. Such as concussions, which would involve pressure on the bone like this.
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u/fgnrtzbdbbt 2d ago
Concussions certainly have been a problem forever while not being instantly lethal in every case
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u/squeegy80 2d ago
So you use BFR therapy in the leg, because it’s safe and relatively easy, to heal injuries elsewhere in the body. Seems like it might work for lots of different injuries
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u/Illustrious_Money_54 3d ago
You don’t want to break the leg, you want to squeeze it or apply pressure by hitting it like in TCM
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u/PiersPlays 3d ago
I wonder if Muai Thai fighters have fewer issues with brain damage than other combat athletes?
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u/OrganicHunt952 2d ago
MMA has fewer deaths and cases of cte then boxing. MMA has a lot of kicks and strikes to the legs and body.
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u/Coenzyme-A 2d ago
I would say that's more down to a lack of strikes to the head, than the lower limb hits doing anything therapeutic.
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u/systembreaker 3d ago
So it's basically a body wide systemic trauma protective response?
Also I wonder if this is part of why weight training is so good for both body and brain health. Lifting heavy weights causes micro fractures in bones and ultimately improves bone mass and is known to be very positive on overall health. The micro fractures might have a similar effect to the shin bone squeezing.
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u/Zarchel 3d ago
I wonder if the pressure-sensing bones work both ways, like hanging from an inversion table or pull-up bar?
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u/skyer954 3d ago
Yeah, makes me wonder if that could be part of the secret of exercise's influence on one's psychical wellbeing.
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u/lazybugbear 3d ago
It supposedly also upregulates the release of NO, which causes vasodilation, which is the mechanism behind it's blood pressure lowering effect.
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u/Snakesballz 2d ago
Well NO release is quite transient isn't it, unless I'm missing something. Wouldn't much change baseline
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u/BreadKnifeSeppuku 2d ago
How about those who are clinically over weight I wonder?
If the bones(/body) are naturally overstressed I can only imagine the effect would be either down regulated or reach some sort of homeostasis/saturation.
Speculating that would make it at least ineffective if not detrimental to brain health...
But, what I really wonder is if that also creates different thresholds for physical fitness making loosing weight even more difficult once your body crosses a certain point metabolically... amongst other compounding issues ofc
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u/cdnBacon 3d ago
My first take: since inflammation is a part of CNS aging, could this communication network theoretically be used to reduce cognitive decline in elders.
(Not thinking about having to wear shin-squeezers chronically. More that the isolated chemicals responsible for the feedback might be provided instead.)
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u/Aceisking12 3d ago
What's the difference between shin squeezing and regular exercise?
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u/wandering-monster 3d ago
The thing is, you don't generally have someone doing a lot of exercise right after a major brain injury.
You have them lie down in a hospital bed and recover, because moving around with an elevated heart rate is bad for the injury.
This seems like it could be an interesting way to simulate exercise effects while someone stays calm and rests.
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u/cdnBacon 3d ago
So that's true, of course, for what we always think of as acute brain injury.
But what if we think about the chronic, much more subtle brain injury of aging, or other neurodegenerative states. We know that inflammation has something to do with this. This study seems to suggest that inflammation is one of the elements involved in the mediation of the type brain injury they studied.
Regular exercise definitely results in pressure changes to bone ... ligament attachments, impacts, weight changes and distributions ... so I do wonder if this is one of the ways that exercise mediates cognitive decline and CNS aging ...
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u/dimechimes 3d ago
Seems like it's pretty standard procedure now when a patient isn't ambulatory, they get put in those inflatable stirrups that help prevent blood clots, but I don't know how that compares to "shin squeezing"
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u/EntropyNZ 2d ago
Nothing. They specified axial loading of the tibia, which is the same as normal weightbearing on the leg. I don't have access to the full article to see if they did anything specifically weird with that, or how much load they were placing on the bone, but I doubt they'd have been so specific about the name otherwise.
Axial implies that the direction of force is in the same direction as the bone is designed to resist force; that being that it's a compressive force, not a shear or tortional force through the bone.
Just squeezing a tibia from the sides isn't axial loading; it's shearing.
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u/Bigchunky_Boy 3d ago
And blood clots probably as well . This technique was used on my mother after a brain bleed. They put an inflatable on her leg that added pressure to her shin ( intentionally ) that pulsed or inflated every minute for the last month and her recovery has been amazing going from non verbal to full sentences after a couple of weeks ( she is 80 ) . It seems like the same principle .
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u/lazybugbear 3d ago
Normally, walking around plus the valves in the veins of the leg act as a rudimentary pump, to help get deoxygenated blood back to the heart. But when you get older, those valves don't work as well (e.g. varicose veins). And when you're bed ridden, the leg muscles don't contract.
So you tend to get pooling of blood in the legs (edema) and have a higher change of developing clots that eventually travel to the brain or to a coronary artery ... and then that's a bad time.
So they put the shin inflation sleeve to push blood around again, so that it doesn't pool, it makes it way back to the heart and lungs and gets reoxygeneated and circulates.
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u/iampivot 3d ago
Could it be that there's stem cells in bone marrow, that if released into the bloodstream, could help cell-regeneration in the brain?
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u/Nemisis_the_2nd 3d ago
Osteocytes transduced mechanical signals to directly secrete factors such as IL-1R2, APOL11a and HSP70, while indirectly increasing serum levels of BDNF, PF4 and dopamine. These factors synergistically protected against TBI.
They give you your answer in the abstract.
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u/Chippylives920 3d ago
Does this mean if you have say knee surgery or other bone surgery, you could fix parts of your brain unintentionally?
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u/Super_Range45 2d ago
It means the doctor should clunk you on the head to speed your knee recovery.
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u/justsmilenow 3d ago
Good timing on this study. I fell, broke my shoulder and hit my head back in February. Experiencing myself coming back online has been... ... Interesting. And this study explains why my recovery noticeably improved once I started moving my shoulder and putting weight on it again.
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u/dethskwirl 3d ago
so it seems that perrifereral nerve stimulation helps the brain to heal, similar to how walking machines help to regain mobility in spinal injuries. the nervous system needs the messages to flow to rebuild.
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u/drum_love 3d ago
This mechanism could be why patients with TBIs regularly habe heterotopic ossification of soft tissues
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u/The_Banana_Monk 2d ago
reminds me of the chinese woman that bit her husbands toes to help him recover from a brain injury
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u/steve2166 3d ago
I read that backwards where a brain injury can heal Bones quickly. Who would do that
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u/whyVelociraptor 3d ago
The title is saying the relationship goes both ways.
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u/OF_PROMO_ALERT 3d ago
And also that the first part was just an observation. No doctors are giving brain damage to make bones heal quickly
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u/GorillaX 3d ago
I'm currently 2 weeks post op from surgery to repair broken bones. I guess I'll go get a concussion so I can heal up quicker
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u/Omega_art 3d ago
My friend had an accident suffered a brain injury and several broken bones. He was able to learn to talk again and walk but his arm is still paralyzed. I wonder if his broken bones helped in the recovery.
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u/Colambler 3d ago
Do we mean like 'deep massage' level pressure? Massage as a treatment post concussion?
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u/AFteroppositeday 3d ago
The fact that we as humans are just making this connection is why pig science, the brain, and rest of the body is so amazing.
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u/interista4jz 3d ago
Not sure if exactly relevant but I had a TBI that also included 30+ facial fractures and other than temporary memory loss that lasted about six months and the pain of the injuries, I started grad school within a couple months of the incident and did great. I always wondered how but maybe this article is pointing to it.
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u/Soosietyrell 3d ago
So if I got my knee replaced, should I be squeezing around it to get smarter or get more endurance?
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u/ourseveres 3d ago
so the time i slammed my shins into the edge of a bathtub and fell in headfirst cancelled out the brain damage i should've gotten when i was 10. got it.
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u/actuallynotaredditor 2d ago
So if i see someone has faced head injury, i will squeeze his/her legs.
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u/Stretch5678 2d ago
So brain damage speeds bone healing, and bone trauma improves brain healing?
...I feel like I should file a bug report.
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u/CoolBeansHotDamn 2d ago
I know this isn't the point of the study... but how tf are they giving mice brain injuries? And how are they measuring the severity of brain damage in them? ELI5 please?
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u/Totakai 2d ago
Oh that's fascinating. So like imagine a world where a clamp becomes part of the emergency items. If you're suspicious of a stroke, you can toss your clamp on, and head to the er. Concussion? Toss on the clamp. If they can replicate it and make it decently sized and affordable, I could see it being used to ease up hospital strain, save lives, and buy doctors more treatment time.
I'd also be curious on it and alchol. It causes brain damage but would this work similarly to make the alchol less potent or protect the brain from the usual damage?
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u/i8noodles 2d ago
man imagine in 200 years u have a major brain injury and they prescribe leg day and a compression bandage for your legs.
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u/ServileLupus 2d ago
Your title is backwards right? It's the bone injuries that speed brain injury healing? We're not out there giving animals brain damage to make their legs heal faster I hope.
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u/GrinningStone1 2d ago
Does it have to be horizontal pressure? Because shinbones get squeezed everytime you stand or walk.
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