head cleaning

Weizmann Institute scientists have developed a new method to treat head injuries, strokes and degenerative diseases of the brain

 
Prof. Vivian Teichberg. Drainage pumps
A head injury, stroke or disease cause large amounts of the neurotransmitter glutamate to be released from the damaged brain cells. In a normal state, this substance plays a role in transmitting signals between nerve cells in the brain. But when it floods the areas adjacent to the affected area, it causes overstimulation, setting off a chain reaction that causes irreversible damage to the brain tissue. 
To deal with this harmful process, Weizmann Institute scientists have developed a new method for removing excess and dangerous glutamate from the brain. The medical treatments that have been tried in this field so far have been based on medicinal substances designed to thwart the harmful activity of glutamate. The problem is that many drugs cannot cross the blood-brain barrier, and therefore cannot reach the scene of activity in the brain at all. Other treatments have not proven themselves in clinical trials. At this point, Prof. Vivian Teichberg from the Department of Neurobiology at the Weizmann Institute of Science entered the picture. Together with Prof. Yoram Shapira and Dr. Alexander Zlotnik from the Soroka Medical Center and Ben-Gurion University of the Negev, Prof. Teichberg was able to show that by activating a certain enzyme in the blood it is possible to drain the glutamate from around the damaged brain cells and transfer it into the bloodstream. In an experiment carried out on rats, the researchers were able to prevent the majority of the damage in this way. Soon the method will be tested in clinical trials (in humans).
The brain has a system for draining and recycling glutamate, but after an injury or illness, this system is unable to deal with the large amount of glutamate secreted by the damaged cells. Prof. Teichberg decided to look for another way to solve the problem. Instead of inhibiting the glutamate, he chose to transfer the excess glutamate, from the fluid around the brain cells, into the blood. In fact, the concentrations of glutamate in the blood are much greater than the concentrations of this substance in the brain, so the brain must activate special "pumps", called "transporters", which draw the glutamate from the brain into the blood. These pumps, which are found in the outer layers of the blood vessels in the brain, collect and concentrate the glutamate, and thus they create near them areas where there are high concentrations of glutamate, and allow the glutamate to exit into the blood.
Prof. Teichberg found a way to influence the efficiency of the transporters, by treating the concentration of glutamate in the blood. When the concentration of glutamate in the blood decreases, the force that "pulls" the glutamate from the brain into the blood becomes stronger. Prof. Teichberg discovered that it is possible to reduce the concentration of glutamate in the blood using an enzyme called GOT that is found in the blood. This enzyme binds to glutamate, disables it, lowers the concentration of glutamate in the blood, and thus causes the pumps (the transporters) to increase their activity, and transfer excess amounts of glutamate from the brain to the blood. In experiments on rats, the researchers were able, in this way, to prevent most of the damage that could have been caused by the release of large amounts of glutamate from damaged nerve cells in the brain.
The "Yade" company, which promotes industrial applications based on the inventions of Weizmann Institute of Science scientists, registered a patent for the method, and granted the "Braintact" company a license to develop a drug based on it. The US Food and Drug Administration, FDA, decided to fast-track the approval process for the drug developed by "Braintact" according to the license it received from "Yida".
If the method proves itself in the clinical trials, it may be used to treat head injuries and strokes, as well as to prevent damage that may be caused to the brain from nerve gas or as a result of bacterial inflammation of the meninges. The scientists say that it is possible that in this way it will also be possible to help those suffering from other diseases, such as ALS, glaucoma, and brain injuries caused by AIDS patients. Prof. Teichberg: "We believe that the method we developed will work in places where other methods have failed, because instead of trying to inhibit glutamate activity, it drains and transfers it from the brain to the blood, where it cannot cause damage."     
 
 
Right: Prof. Yoram Shapira and Dr. Alexander Zlotnik. Science in the service of medicine
 

Pictured: damaged brain sections of rats. Left: no treatment. Right: after draining glutamate from the brain into the blood. Above: An oval shade marks healthy cell nuclei in the treated tissue. These are almost completely absent in the untreated tissue (left). Middle: The yellow line that appears in the untreated tissue shows degenerated cells. Below: The brown line in the treated tissue shows healthy cells, which are missing in the image on the left

tying a love story 
 
A team of researchers from the Weizmann Institute of Science and the Pasteur Institute in France characterized the structure of the glutamate binding site in the glutamate receptor molecule. Glutamate is one of the most important communication substances in the brain, and is involved, among other things, in learning and memory processes. Therefore, knowing the structure of the molecule that absorbs (and binds) glutamate may promote studies in the field of learning and memory, and in the future - also the development of drugs to strengthen memory.

In addition, the discovery may help in the development of treatment methods for brain disorders related to glutamate, such as stroke, epilepsy ("falling disease") and more.

In order to learn about the spatial structure of the receptor, the researchers proposed computer models, which were based on the sequence of amino acids that make up the protein receptor molecule, and on experimental structures of bacterial proteins, which appear to be the evolutionary ancestors of the glutamate receptor.

Laboratory experiments verified one of the models and explained the binding mechanism of the receptor. The research was carried out by Prof. Vivian Teichberg, Dr. Yoav Paz and Dr. Miriam Eisenstein from the Weizmann Institute of Science, in collaboration with Prof. Anne Deviller-Thierry from the Pasteur Institute in France.