Aug. 30 (UPI) -- Researchers have developed a therapy that regrows fibers after spinal cord injury in rodents, offering potential as a way to restore function like hand strength and bladder control in humans.
Neuroscientists at UCLA, Harvard University and the Swiss Federal Institute of Technology collaboratively identified a three-pronged treatment that triggers tiny fibers that link nerve cells and enable them to communicate. Not only did these axons grow through scars, they could also transmit signals across the damaged tissue, the scientists found.
The research was published Wednesday in the journal Nature.
"The idea was to deliver a sequence of three very different treatments and test whether the combination could stimulate disconnected axons to regrow across the scar in the injured spinal cord," lead author Dr. Michael Sofroniew, a professor of neurobiology at the David Geffen School of Medicine at UCLA, said in a press release. "Previous studies had tested each of the three treatments separately, but never together. The combination proved to be the key."
When spinal cords are injured, the brain is unable to send signals to neurons below the injury site because of damage to the axons.
Researchers have known human nerve fibers need three things to grow: genetic programming to switch on axon growth, a molecular pathway for the fibers to grow and a trail of protein "bread crumbs" that encourage them to grow.
These three conditions are active as humans develop in the womb. But, after birth, these processes shut down as the genes that control the growth programs are still dormant in the body.
Using a tree analogy, researchers noted if the main branches are cut, little branches may sprout spontaneously along the remaining trunk of the tree but the cut ones do not grow back.
With neurons in adults, new branches of severed axons can sprout and connect above an injury, but the severed part of the axon does not regrow. The three-pronged method makes it possible to regenerate entire axons.
"We've regrown forests of axons," senior author Gregoire Courtine of the Swiss institute said in a press release.
Researchers reactivated nerve cells in mice's spinal cords using an injected treatment carried in harmless viruses developed in the lab of Zhigang He, a neuroscientist at Harvard.
The UCLA team anesthetized the animals two weeks later and disconnected the axons in their lower spinal cords.
Two days afterward, the team administered a second treatment into the lesion to create new pathways on which axons prefer to grow.
A third set of molecules called chemo-attractants were later injected.
"Not only had axons grown robustly through the scar tissue but many fibers also had penetrated into the remaining spinal cord tissue on the other side of the lesion and made new connections with neurons there," Sofroniew said.
Researchers repeated the experiment in mice at UCLA and in rats in Courtine's lab in Switzerland. The results confirmed their original findings.
And when they tested whether newly regrown axons in live animals could conduct electrical activity, they saw some other good news.
"When we stimulated the animal's spinal cord with a low electrical current above the injury site, the regrown axons conducted 20 percent of normal electrical activity below the lesion," Sofroniew said. "In contrast, the untreated animals exhibited none."
But the rodents ability to move did not improve.
"We expect that these regrown axons will behave like axons newly grown during development -- they do not immediately support coordinated functions," Sofroniew said. "Much like a newborn must learn to walk, axons that regrow after injury will require training and practice before they can recover function."
Researchers next want to retrain newly wired circuits to restore movement.
"Now we need to investigate the requirements so that the axons make the appropriate connections with locomotor circuits below the injury," leader author Mark Anderson of Swiss Federal Institute of Technology and UCLA. "This will entail rehabilitation with electrical stimulation to integrate, tune and functionalize the new axons so that the rodents can walk again."