To repair the damage of spinal cord injuries, researchers must do more than regenerate nerve fibers called axons. These nerve fibers, which send electrical-impulse signals, must also form synapses with the correct neurons. In a study published in the September Nature Neuroscience, researchers successfully guided axon growth toward target neurons for the first time.
Investigators at University of California, San Diego, severed a specific group of axons in rats’ spinal cords. They also injected the rats’ brain stem with neurotrophin-3 (NT3), a growth factor known to attract the axons. The rats received two NT3 injections, one in an area where the axons would usually connect to neurons and another where the axons typically would not grow.
After filling the spinal cord lesions with cells derived from bone marrow—which served as a bridge for the regenerating nerve fibers—the researchers waited about four weeks for the axons to develop. To determine where those axons grew, they used high-resolution microscopy to find the location of tracers (special molecules that travel up the axons after being injected into the rats). The result: Axons formed a connection with neurons wherever NT3 was present, even in those areas where they would not normally grow.
The researchers were surprised to see the axons guided so precisely by the growth factor, says lead author Laura Taylor Alto.
“It was a powerful attractant to the axons. We could get them to grow basically anywhere, based on that result,” says Alto, now a post-doctoral fellow at the University of Texas Southwestern Medical Center.
But when researchers ran further tests on the synapses, they discovered a communication breakdown. The axons’ electrical signals were not transmitting across the spinal injury and could not reach the new synapses. Alto says one possible explanation is a lack of myelin, the insulation that wraps axons and allows them to transmit signals quickly. The axons that grew through the injury area had little or no myelin. Alto notes that future research might tackle that problem by filling the spinal injury site with cells such as oligodendrocytes that help re-myelinate axons.