A synthetic blue dye commonly used in food coloring could protect damaged spinal cords from a second wave of injury brought on by inflammatory response to the damage, according to a study in this week's Proceedings of the National Academy of Sciences.

When a spine is crushed -- but not severed -- patients often gets worse two to three days after the initial injury, when inflammatory cells inundate the spinal cord. The immune cells are "recruited to clean up the mess, but if you get too many, they spit out reactive oxygen species," explained George Dubyak from Case Western University in Cleveland, Ohio, who was not involved in the research. The inflammation causes additional injury to the spinal tissue, he said.

Rat treated with Brilliant blue G dye Image: Takahiro Takano

A team led by Steven Goldman and Maiken Nedergaard at the University of Rochester in New York was searching for a compound that could block that inflammation, as well as cross the blood brain barrier to reach the central nervous system. In previous studies, Goldman and Nedergaard had investigated how the levels of ATP -- an essential energy metabolite and inflammatory mediator -- affect spinal cord injuries. ATP is normally released from injured cells for a few minutes after injury, they found, but it can also be released for up to six hours in a damaged spinal cord, potentially prolonging the inflammatory signal. They showed that blocking one of the receptors for ATP protected the spine from inflammatory damage.

The ATP receptor blocker they used, however, was too big to cross the blood-brain barrier and had to be injected directly into the spines of rats -- an undesirable procedure for spinal injury patients. In searching for other compounds with a similar chemical structure, they came across Brilliant Blue G (BBG), an analog of a dye called FD&C Blue No. 1 -- one of the safest food colorants used today. (FD&C stands for Federal Food Drug and Cosmetic Act.)

When Goldman and Nedergaard injected the dye into rats with spinal cord injury, not only was it able to cross the blood brain barrier, it reduced the inflammation and the size of the injured area. After about 10 days, the rats treated with blue dye began using their hind legs to a greater degree than control rats, scoring at least two points higher on a 21-point rating of locomotor abilities. "They are not cured," said Nedergaard, but they had "better bladder control, and they can walk."

The researchers checked the rats for typical physiological indicators of toxicity such as blood pressure, body temperature, blood pH, weight, and behavior. Other than turning the albino rats a subtle shade of blue, BBG had no detected side effects. "They're running around very happy while they're blue," she said.

"Right now [most] patients are offered no treatment" for spinal cord injury, said Nedergaard, adding that steroids are administered in some cases, but their efficacy is debated. Goldman is hoping to initiate the first clinical trial for the dye in patients this fall, she said, but other similarly acting molecules will be needed. "I think that the inflammatory responses cannot be targeted by just one drug," she said.

It's still unclear how well the dye will work in humans, Dubyak said. Only a small percent of the injected dye makes its way through the blood brain barrier. According to cell-based assays, BBG is less effective as an ATP receptor inhibitor than in rats, he said, so an even bigger dose may be needed to see an effect.


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