Scientists have shown that it is possible to guide regenerating axons-severed wires of the spinal cord, to their correct targets and re-form connections after spinal cord injury.
Past studies have shown that axons can be induced to regenerate into and beyond sites of experimental spinal cord injury.
AdvertisementHowever, a key question has been how these regenerating axons, on reaching the end of an injury site, can be guided to a correct cell target when faced with millions of potential targets.
Scientists at the University of California, San Diego School of Medicine have also been trying to figure out whether regenerating axons can form functional, electrical connections called synapses.
"The ability to guide regenerating axons to a correct target after spinal cord injury has always been a point of crucial importance in contemplating translation of regeneration therapies to humans," Nature Neuroscience quoted senior author Mark Tuszynski, a professor of Neurosciences and director of the Center for Neural Repair at UC San Diego, and neurologist at the Veterans Affairs San Diego Health System.
"While our findings are very encouraging in this respect, they also highlight the complexity of restoring function in the injured spinal cord," he added.
During the study, the researchers looked at regenerating sensory axons in rat models of spinal cord injury.
Sensory systems of the body send axons into the spinal cord to convey information regarding touch, position, and pain. Many sensory axons are covered by an insulating myelin sheath, which helps these impulses travel efficiently to the brain.
In certain spinal cord injuries, the axons are severed and the myelin sheath damaged, resulting in an inability to feel or sense the body.
The axons can no longer link to their targets in the brain, which blocks the electrical impulses from reaching the central nervous system.
The current study has shown that it is possible to guide regenerating axons to correct targets using a type of chemical hormone called a growth factor.
The research team used a type of chemical hormone, a nervous system growth factor called neurotrophin-3 (NT-3), to guide regenerating sensory axons to the appropriate target and support synapse formation.
They say that regeneration required two other treatments at the same time: placing a cell bridge in the spinal cord injury site to support axon growth, and a "conditioning" stimulus to the injured neuron that turned on regeneration genes for new growth.
When the growth factor was placed in the correct target as a guidance cue, axons regenerated into it and formed synapses. When the growth factor was placed in the wrong target, axons also followed the growth factor and grew into the wrong region.
The researchers used high-resolution imaging systems to show that regenerating axons guided to the correct cell formed synapses that were precisely on target.
They say that the axons contained rounded vesicles - small packets at the end of the axon, packed with the chemical messengers needed to support electrical activity in the newly formed circuit.
However, the connections were not electrically active, likely because the regenerating axons were not covered in myelin, the insulating material of the nervous system.
"Restoring axonal circuitry is complex, requiring several concurrent therapies to achieve axonal regeneration into and beyond a spinal cord lesion site. But, just as an electrical circuit needs insulation so it doesn't short-circuit, it appears that these regenerating axons require restoration of the myelin sheath to ultimately restore function," said Tuszynski.
This will be the next step in the team's research.
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