Jan. 24, 2007 - When brain cells die, whether from head trauma, stroke or disease, a substance called glutamate floods the surrounding areas, overloading the cells in its path and setting off a chain reaction that damages whole swathes of tissue. Glutamate is always present in the brain, where it carries nerve impulses across the gaps between cells. But when this chemical is released by damaged or dying brain cells, the result is a flood that overexcites nearby cells and kills them.
A new method for ridding the brain of excess glutamate has been developed at the Weizmann Institute of Science. This method takes a new approach to the problem, compared with previous attempts based on drugs that must enter the brain to prevent the deleterious action of glutamate. Many drugs, however, can't cross the blood-brain barrier into the brain, while other promising treatments have proved ineffective in clinical trials. Prof. Vivian Teichberg, of the Institute's Neurobiology Department, working together with Prof. Yoram Shapira and Dr. Alexander Zlotnik of the Soroka Medical Center and Ben Gurion University of the Negev, has shown that in rats, an enzyme in the blood can be activated to "mop up" toxic glutamate spills in the brain and prevent much of the damage. This method may soon be entering clinical trials to see if it can do the same for humans.
Though the brain has its own means of recycling glutamate, injury causes the system to malfunction, leading to glutamate build up. Dr. Teichberg reasoned that this problem could be circumvented by passing glutamate from the fluid surrounding brain cells into the bloodstream. But first, he had to have a clear understanding of the mechanism for moving glutamate from the brain to the blood. Glutamate concentrations are several times higher in the blood than in the brain, and the body must be able to pump the chemical "upstream."
Glutamate pumps, called transporters, are found on the outsides of blood vessels, on cells that come into contact with the brain. These collect glutamate, creating small zones of high concentration from which the glutamate can then be released into the bloodstream.
Basic chemistry told him that he could affect the transporter activity by tweaking glutamate levels in the blood. When blood levels are low, the greater difference in concentrations causes the brain to release more glutamate into the bloodstream. He uses an enzyme called GOT that is normally present in blood to bind glutamate chemically and inactivate it, effectively lowering levels in the blood and kicking transporter activity into high gear. In their experiments, Teichberg and his colleagues used this method to scavenge blood glutamate in rats with simulated traumatic brain injury. They found that glutamate cleared out of the animals' brains effectively, and damage was prevented.