University researchers led by Professor Bonnie Firestein may have found a treatment for spinal cord injuries by using uric acid.
Firestein, an associate professor of cell biology and neuroscience, and her team have published their findings in the early online copy of the research journal Glia.
Humans produce only small quantities of uric acid naturally, but past research indicated the human body is very sensitive to uric acid blood concentration. Gout, an extreme form of arthritis, results from an excess of uric acid, leading to the formation of uric acid crystals in the cartilage and tendons of joints. These crystals result in tremendously painful inflammation.
However, recent research points to the detrimental effects of low blood uric acid concentration.
"In the literature, there's a lot of data on uric acid as a protective agent in multiple sclerosis and Parkinson's disease," Firestein said. In fact, people suffering from gout rarely develop multiple sclerosis or Parkinson's disease.
Therefore, scientists proposed that a dearth of uric acid may promote certain neurological problems in the body.
Firestein's laboratory initiated the study of uric acid's effects on the central nervous system because cypin, a protein Firestein researched for years, is involved in the production of uric acid.
"We first wanted to reveal a possible relationship between cypin, uric acid and the neuronal protection," said Dr. Yangzhou Du, a research associate in Firestein's laboratory and the first author on the paper.
The lab's findings point to an intricate interaction between glia cells and uric acid to prevent damage to neurons.
There are two types of nerve cells in the central nervous system: neurons and glia. Neurons were previously thought to be the most important cells in the nervous system; much research has been done on them. Glia cells, though they outnumber the neurons in a ten to one ratio, were dubbed as "supporting cells," said Firestein.
In spinal cord injuries, the spinal cord suffers two forms of damage. Mechanical damage results from the physical impact on neurons, and chemical damage results from "neurons [that] release glutamate in an injury, which can kill neurons at high amounts," Firestein said.
Du's team simulated a spinal cord injury in the laboratory by adding glutamate to neurons and glia grown on a plate, he said.
He explained that when exposed to uric acid, one type of glia cell called astroglia expresses an elevated level of a glutamate transporter called EAAT-1. The astroglia are then able to reduce neurons' access to glutamate, protecting them from further damage.
Uric acid was also shown to protect neurons even when it is added after glutamate. "This points to therapeutic potential," Du said.
However, prescribing uric acid may not be the best avenue for treatment against glutamate toxicity, Firestein said. Though uric acid can be administered through local injections or with an oral supplement called inosine that is internally degraded to uric acid, Firestein said high uric acid concentrations may be toxic to the heart and kidneys.
Firestein is now collaborating with researchers from the University of Rochester and Baylor College of Medicine to "develop astroglia from stem cells that express high levels of the glutamate transporter." These modified astroglia will be transplanted into rats with a spinal cord injury to see if they will ameliorate their conditions.
A $205,000 grant from the New Jersey Commission on Spinal Cord Research supported the project.
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