"In the paper, we showed that uric acid modulates peroxynitrite's effects," Dr. Hooper says. "It's incredibly useful in preventing the damage related to peroxynitrite as a toxic molecule. More importantly, it stops the secondary injury cascade by preventing the neutrophils from getting into spinal cord tissues through the blood-brain barrier."
Dr. Hooper and his co-workers compared injured rats that received saline to spinal cord-injured rats that were given uric acid. "The injury causes a tremendous amount of damage in the mice less than 50 percent range of motion in one or two hind limb joints remain immediately following the injury," he says. Those given saline had regained movement of up to two or three joints. The uric acid-treated rats recovered to where they could support their own weight, despite having some disabilities due to the damage.
Next, the scientists want to better understand how the peroxynitrite-mediated processes actually work, which is particularly important to learning how to control immune responses in the central nervous systems of both in mice and humans. "We're looking at various models to distinguish between peroxynitrite pathology and its effects on blood-brain barrier function," he says.
"We want to establish the precise timing where the inactivation of peroxynitrite will have therapeutic benefit," he says. "In the spinal cord, we know many of the changes occur within 24 hours. It's certainly feasible to give someone uric acid immediately and raise levels in 50 minutes. Whether or not this should be a first-line response is unknown.
"There is a range we could work with in raising levels before there's a problem, such as in gout," he says, referring to an ailment characterized by excessive uric acid. "We know that the human uric acid baseline is higher than that in mice, but we also know that the damage
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14-Feb-2005