麻豆传媒

Firmly pressing down on shin bones for just a few minutes every day drastically improved movement and cognition in mice and pigs one week after they had a traumatic brain injury. The intervention stimulates bone cells that are sensitive to physical force, causing them to release substances that promote good brain health.

鈥淭his is big news to me, as it reveals a previously underappreciated bone-brain communication system, and could potentially lead to new therapeutic approaches in the future,鈥� says at the Max Planck Center for Physics and Medicine in Germany, who wasn鈥檛 involved in the work.

Traumatic brain injuries are usually caused by a forceful bump, blow or jolt to the head or body, such as during a fall or car crash. with recent head injuries, of which about 40,000 are a traumatic brain injury. Despite decades of effort, no approved drug restores lost brain function after a traumatic brain injury, and physical rehabilitation to improve symptoms has limited benefits.

Previously, studies have shown that , including the brain. at Southern Medical University in Guangzhou, China, and his colleagues have also found change in response to weight-bearing activity, like walking or running, and that by releasing molecules that stimulate bone growth.

This led them to wonder whether this communication goes both ways, which would mean that stimulating bones helps an injured brain. To find out, male mice were given moderate traumatic brain injuries, which can lead to long-term or lifelong health problems in people, while under anaesthesia.

The next day, their shin bones were compressed lengthwise, from knee to ankle, using a mechanical loading device about 15 times their body weight, a force mice can usually tolerate. This was applied for 2.5 minutes per day over five days. The mice鈥檚 motor and cognitive functions were then tested one week and eight weeks after their injuries.

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The researchers found that the treated mice descended a pole more quickly than untreated mice at weeks one and eight, with the former group鈥檚 times being similar to those of mice without brain injuries. In a spatial memory test, where the mice learned to find a hidden platform in water, the mice in the bone-compression group crossed it nearly five times as often as the untreated mice one week after their injuries and about 1.5 times as often after eight weeks.

Buried deep within bone are cells called osteocytes, which contain ion channels called Piezo1 that open when they sense force. In another part of the experiment, the team knocked out Piezo1 in osteocytes in a different group of mice with traumatic brain injuries. Without Piezo1, bone compression had no impact on the mice鈥檚 motor or memory functions.

Next, the researchers took serum 鈥� the liquid portion of blood 鈥� from the treated mice and found it contained elevated levels of three molecules: BDNF (which supports the survival, growth and maintenance of neurons), PF4 (which is involved in inflammation) and dopamine (a neurotransmitter involved in memory and movement). Injecting this serum into untreated mice seemed to transfer the brain benefits, without the need for bone compression.

Mild brain damage may affect memory more than severe injuries

In a small study, memory recall was better in people with more severe damage to a brain region involved with memory, compared with those with milder damage. With severe damage, other parts of the brain may take on the damaged region鈥檚 function

Finally, the researchers repeated the experiment in male adolescent pigs, whose brains are more similar to ours, that were given moderate traumatic brain injuries under anaesthetic. The pigs鈥� shin bones were compressed using a load equivalent to twice their body weight. This led to a reduced loss of neurons and brain tissue, less inflammation and better cognitive performance compared with untreated pigs. The treated pigs also had higher levels of the three molecules in their serum.

None of the experiments caused visible damage or bruising in the mice or pigs. Human shin bones can usually tolerate up to about five times a person鈥檚 body weight without breaking, according to the researchers.

at the University of California, Irvine, says the research needs to be repeated in female animals. 鈥淕iven that oestrogen regulates how bone responds to mechanical load, we need to know whether the effect extends to females.鈥� But if these results carry over to female animals and eventually people, the approach could be very helpful. 鈥淵ou could apply it to someone in an intensive care bed who can鈥檛 exercise,鈥� she says.