Interestingly, this latent, or secondary, injury develops over days and even weeks after the initial injury. It also appears to cause larger, more debilitating lesions in the spinal cord, said Randy Christensen, the study's lead author and a postdoctoral researcher in neuroscience at Ohio State University.
"Preventing over-stimulation caused by glutamate and TNFa together may be a viable strategy for therapeutic intervention after human spinal cord injury."
Receiving the initial brunt of the secondary trauma seem to be the neurons, or the cells in gray matter. As time passes, however, tissue in the white matter is also destroyed by secondary damage. Oligodendrocytes, the main cell type in white matter, begin to self-destruct during the secondary injury.
Oligodendrocytes protect the white matter's axons – long, skinny tails attached to nerve cells that carry nerve cell messages throughout the body.
"These long, fragile extensions of nerve cells are probably very vulnerable," Christensen said.
The researchers presented their results Nov. 12 in New Orleans at the annual Society for Neuroscience meeting. Christensen conducted the study with Jacqueline Bresnahan, a professor of neuroscience at Ohio State, and Michael Beattie, the chair of Ohio State's neuroscience department.
The researchers injected glutamate, tumor necrosis factor-alpha (TNFa) or both molecules into the spinal cords of healthy, uninjured rats. Glutamate is a neurotransmitter, while TNFa is a potent cell stimulator – its function includes stimulating the body's immune response after injury. Both are released in dangerously high concentrations at the site of a spinal cord injury.
Christensen and his colleagues suspect that glutamate and TNFa work in tandem, essentially over-stimulating the tissue surrounding the original site of damage, causing the surrounding cells to "go into shock" and die.
In these experiments, the rats' spinal cords weren't injured, but the injections of glutamate and TNFa mimicked the effects of secondary injury. A group of control rats was injected with albumin, an innocuous protein, to make sure the injection itself hadn't caused the secondary injury.
The researchers found a delayed reaction . . . the axons near the injection site began breaking two days after injection. In related work, these researchers have found evidence of axons breaking up to fourteen weeks after an injury.
"While we're not sure why the axons begin to break so long after the initial injection, the cells meant to help the wound heal may get overly excited – so much so that they destroy the axons," Christensen said. "Another possibility is that the protective oligodendrocytes take a couple of days to die, finally exposing the bare axons to damage.
"Preventing over-stimulation caused by glutamate and TNFa together may be a viable strategy for therapeutic intervention after human spinal cord injury."
While there was noticeable nerve cell loss and tissue damage in gray matter 90 minutes after injections, the axons were not affected at this point in time.
By day two after the injection, however, there were large lesions in the white matter surrounding the injection site as well as noticeable damage to the axons.
"The time course is pretty important, because in spinal cord injury, many of the cells don't die until long after the initial injury," Christensen said. "Dying neurons might release glutamate and TNFa, and that release eventually kills neighboring nerve cells, oligodendrocytes, and axons."
This research was supported by a grant from the National Institutes of Health.
Contact: Randy Christensen, 614-247-6869; Christensen.40@osu.edu
Written by Holly Wagner, 614-292-8310; Wagner.235@osu.edu