Dying nerves cause even more harm after spinal cord injury

By HOLLY WAGNER, Research Communications

A new study in rats has found that after severe spinal cord injury, molecules intended to help nerves communicate can attack the tissue surrounding the initial injury and cause further damage.

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.

Randy Christensen     By Jo McCulty

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 also is 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 14 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.

Bacteria use novel mechanism to express genes

New research on how bacteria make compounds critical to their survival may help scientists create antibiotics for controlling dangerous bacterial pathogens. For decades scientists believed that gene regulation in bacteria depended solely on regulatory proteins. But new findings have altered those beliefs. In the current study, the researchers found that bacteria use RNA to directly measure a signal and to control the related genes, rather than using a messenger protein to shuttle information to the gene.

"Until recently, we didn't think that RNA could bind signal molecules in bacterial cells," said Tina Henkin, the study's lead author and a professor of microbiology. Henkin and her colleagues looked at how Bacillus subtilis, a harmless bacteria, makes the amino acid lysine. Lysine is a crucial ingredient in making protein and in building bacterial cell walls. Although B. subtilis is innocuous, it's a cousin of Bacillus anthracis, the pathogen that causes anthrax.

"Figuring out how pathogens control their genes could help in developing antibiotics for some of medicine's worst enemies," Henkin said. "We are quickly running out of effective antibiotics, as the bacteria develop resistance to the ones we have."

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