Leading an active lifestyle may increase the likelihood of damaged nerves regenerating after a spinal cord injury, according to research published in Science Translational Medicine.
An international team, led by researchers from Imperial College London, suggests that providing rodents with more space, an exercise wheel, toys and company before an injury helped to “prime” their cells, making it more likely their damaged nerves would regenerate following spinal injury.
The researchers were also able to mimic the effects of an active lifestyle by using a drug that targets the same underlying pathways in the cells — “reprogramming” the nerve cells to regenerate following a spinal injury.
While the work is still at an early stage the findings open a “realistic pathway” towards testing the links between pre-existing active lifestyle and recovery from spinal injury, and potentially to clinical trials of their drug treatment in human patients, a media release from Imperial College London explains.
Professor Simone Di Giovanni, from the Department of Medicine at Imperial, whose team led the research, said: “Anecdotal evidence suggests that people with an active lifestyle may recover to a greater degree after spinal cord injury than those who are less active,” says Professor Simone Di Giovanni, from the Department of Medicine at Imperial College London, whose team led the research, in the release.
“Our studies support these findings. From what we have seen it’s almost as if the nerve cells are being ‘primed’ for regeneration and growth, which add to this enhanced recovery.”
In the study, researchers discovered that stimulating nerve cells through environmental enrichment before an injury can help to promote regeneration of the nerve fibers, leading to more regrowth at the site of damage.
“We discovered that environmental enrichment such as housing mice in a larger cage than usual, with more mice in it, more toys, tunnels, swings, running wheels, etc, increases the activity of neurons,” Di Giovanni states.
“This leads to changes in gene expression, which make the nerve more likely to regenerate. Essentially, by increasing the activity of neurons that sense enriched environmental stimuli we have been able to promote the regenerative potential of nerves after spinal cord injury.”
They found that when mice were generally given more environmental, physical or social stimuli, their nerve cells were altered, boosting their potential to regenerate compared to control mice which had a basic level of enrichment. When nerves from enriched animals were subsequently damaged, the effects of the active lifestyle led to more growth and sprouting of the nerve fiber at the site of injury.
“Although the findings that an active enriched lifestyle before injury can enhance the regenerative potential of nerve cells is exciting, humans that live enriched lives do not fully recover. This led us to further investigate the underlying cellular mechanisms to identify a therapeutic target that could be exploited after injury,” comments first author Thomas Hutson, from the Department of Medicine at Imperial, in the release.
The researchers identified a key molecule called CREB-Binding Protein (CBP) that may be effectively reprogramming the nerve cells, altering the expression of a number of genes in the cells and boosting their ability to regenerate.
Based on this, the team used a recently developed drug that activates CBP to reprogram damaged nerve cells, mimicking the regenerative effect of environmental enrichment.
In trials with mice and rats, they found that giving the drug 6 hours after spinal injury (and once a week thereafter) promoted the regeneration and sprouting of damaged nerve fibers. Following injury and drug treatment, rats which were otherwise unable to walk properly regained significant mobility in their back legs, compared to control animals without treatment, the release continues.
The researchers highlight that the study was limited as the findings are from rodents with relatively controlled spinal damage (compared to the variability in location and severity in human injuries), but add that pending safety studies and work in larger animal models, the drug has the potential to move to early stage clinical trials in future.
“The drug treatment that promoted regeneration and recovery in mice and rats after spinal cord injury offers an opportunity to be tested in patients,” Di Giovanni concludes.
“In principle, this kind of treatment is not very far from being tested in the clinic. Further studies are needed to show the drug is safe in humans, before it could be trialed. But in future it could potentially be combined with neurorehabilitation in clinical trials.”
[Source(s): Imperial College London, Science Daily]