Olfactory neurons, the cells that carry information about scents to the brain, are surrounded by caretaker cells that nourish and insulate them. Unlike other cells in the brain or spinal cord, olfactory neurons can regenerate, thanks in large part to their able assistants.
A new study shows that these service-oriented cells, called olfactory ensheathing glia, can also build bridges in damaged spinal cords. Scientists in Spain disabled the hind limbs of nine rats by severing their spinal cords, then promptly injected olfactory glial cells at each severed end. Within 7 months, all the rats recovered partial movement in their hind legs, the researchers report in the February Neuron. They theorize that the glial cells provided growth-promoting chemicals to the severed cells.
“This the most impressive level of [nerve] regeneration after complete spinal transection that I’ve ever seen. It’s certainly very exciting,” says Eric Frank, a neurobiologist at the University of Pittsburgh School of Medicine. “At the same time, this field is historically filled with amazing reports that turn out to be difficult to replicate. We have to be cautious.”
Severing the spinal cord cuts the axons, the long tendrils of neurons that extend up and down the spinal cord. Axons carry messages to and from the brain.
In the recent test, the ends of the spinal cord retracted immediately after the injury to leave a gap of up to 3 centimeters. The rats were unable to support their weight on their back legs or use them to climb. Three to 7 months later, severed axonal ends gradually reconnected in the spines of the rats treated with the glial cells.
The animals regained some ability to use their back legs and climb a mesh grid pitched at a 45º angle. The rats also appeared to recoup some sensation in their hindquarters, says study coauthor Almudena Ramón-Cueto, a neuroscientist at the Spanish Council for Scientific Research in Valencia. Twelve other rats that received the same injury but no glial cells remained unable to use their hind legs throughout the study.
William D. Snider, a neuroscientist at the University of North Carolina at Chapel Hill who has seen a videotape of the rats, says several of those getting the glial-cell treatment “could really navigate the grid,” climbing slopes of up to 90º.
The improvement is remarkable, Snider says, considering that the injury to these rats “is more extreme than humans would usually suffer.” Most spinal-damage patients have crush injuries, which can leave some axons intact.
The new technique is promising because, theoretically, ensheathing glial cells could be taken from an individual’s own brain and transplanted into the injury site, says Wise Young, a neuroscientist at a Rutgers University laboratory in Piscataway, N.J. Such patients wouldn’t need to take immune-suppression drugs to forestall tissue rejection. The procedure would also avoid the ethical controversies associated with research and treatments using fetal cells, he says.
Olfactory ensheathing glial cells seem capable of this healing because they can migrate from the injection sites, unlike other glial cells, Ramón-Cueto says.
The precise molecular mechanisms underlying the process remain to be determined, Ramón-Cueto says. “We know that olfactory ensheathing glia produce a variety of adhesion molecules and growth factors that might change the inhibitory central nervous system environment.” The Spanish team next plans to test the technique on nonhuman primates.