Brain injury causes glutamate, a substance necessary for proper brain function, to flood areas surrounding the trauma and kill other cells. Weizmann Institute scientists have developed a new way to rid the brain of excess glutamate. This method — which uses an enzyme found in blood — could lead to new therapies not only for brain injury, but also for stroke and other conditions, and holds promise for prevention of damage from meningitis or nerve gas.
An injury to the brain can be devastating. 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 completely 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. Prof. 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.