Diabetes drug may fight traumatic brain injury

Although the death toll in people who suffer from traumatic brain injury (TBI) is relatively low, it can have severe, lifelong consequences for brain function.

TBI can impair a patient’s mental abilities, impact memory and behavior and lead to dramatic personality changes. In addition, the long-term medical treatment carries a high financial cost.

In research commissioned by the US Air Force, Prof.

Chaim Pick of Tel Aviv University’s Sackler Faculty of Medicine and Dr. Nigel Greig of the US National Institute of Aging have discovered that Exendin-4 – an FDA-approved diabetes drug – significantly minimizes damage in TBI animal models when administered shortly after the initial incident.

Originally designed to control sugar levels in the body, the drug has recently been found effective in protecting neurons in disorders such as Alzheimer’s disease.

Pick’s collaborators include his TAU colleagues Dr. Vardit Rubovitch, Lital Rachmany-Raber and Prof. Shaul Schreiber, and Dr. David Tweedie of the US institute.

Explained recently in the journal Experimental Neurology, this “breakthrough” is the first step toward developing a cocktail of medications to prevent as much brain damage as possible following injury, the team said.

Pick has been researching TBI for many years, beginning with the effects of everyday injuries such as hitting the windshield in a car accident. As a result of his work for the US military, he has expanded his research to include trauma sustained when someone is exposed to an explosion, such as during a terrorist attack.

TBI causes long-term damage by changing the chemistry of the brain. During an explosion, increased pressure followed by an intense vacuum shakes the fluid inside the brain and damages the brain’s structure. This damage can’t be reversed, but mapping the injury through behavioral and physical tests is crucial to understanding and quantifying the damage and forming a therapy- or medication- based treatment plan.

The TAU team designed a pre-clinical experiment that exposed mice to controlled explosions from eight and 11 meters away and then analyzed the resulting injuries. They also studied the effect of Exendin-4 as an additional parameter in minimizing brain damage. They divided the mice into four groups: a control group; a second group that was exposed to the blast without medication; a third group that received the medication but was not exposed to the blast; and a fourth group, exposed to the explosion and given the medication within an hour after the blast and continuing for seven days afterwards. (The mice were placed under anesthesia before the explosion so they would not suffer.) Behavioral and physical tests showed that the mice that were exposed to the blast had severely impaired brain function compared to the control group. However, the mice that had also received the Exendin-4 treatment were almost on a par with the control group in terms of brain function, proving that Exendin-4 significantly reduced the long-term damage done by an explosion. In separate experiments, the drug was also associated with an improved outcome in mice who sustained TBI by blunt force.

Pick says this promising discovery can help researchers find the ideal combination of medications to minimize the lasting impact of TBI. “We are moving in the right direction.

Now we need to find the right dosage and delivery system, then build a cocktail of drugs that will increase the therapeutic value of this concept,” he explains. He adds that in treating such traumatic injuries, one drug is unlikely to be sufficient.

GREENERY AND HEALING

With numerous Israeli medical centers around the country building new wings and even whole new buildings, it would be worthwhile for administrators to take into account research on how courtyard gardens and other aesthetic touches – including the inclusion of animals – are important to the well-being and recovery of patients. The Israeli Hebrew-language edition of Scientific American reported in its latest issue that scientific research has proven such elements are beneficial to patients (and probably also to hospital staffers). San Francisco medical writer Deborah Franklin, whose article was translated by the magazine, said that the greener such hospital facilities are, the better.

Bushes, trees that provide shade and flowers that gladden the eye have shown to be desirable, especially if they attract birds. Realistic statues are also loved by patients, as are wide and meandering paths that are made of dark materials (so they don’t blind patients in the sun). Plants and trees that emit pleasant scents and can be safely touched are preferable, and doors to the courtyards should not be so heavy that it’s difficult for people to open them.

Having such places within the hospital grounds where patients can “escape” to speeds up recovery from surgery, infection and disease in general. The research proving these statements were randomized, controlled studies. If such touches cannot be added to old buildings, even hanging large photos of nature spots such as a running stream or a shady forest speeds up recovery of heart surgery patients, the article reported, and were much more effective than abstract paintings or drawings.

FOLLOW YOUR DREAMS

How often do you encourage others to pursue their dreams? How often do you feel caught up in daily hassles that keep you from following your own dreams? Dr. Rachel Barkan of Ben-Gurion University of the Negev and Prof.

Shai Danziger of Tel Aviv University have been trying to understand why it is always easier said than done. Their research, funded by the Israel Science Foundation, examines the differences between choice and advice in a wide variety of situations. In a new research paper Danziger, Barkan and their student, Ronit Montal, demonstrate that advisers tend to promote idealistic options while choosers tend to opt for pragmatic options. The paper was recently published in the prestigious Journal of Personality and Social Psychology.

“It’s a matter of seeing the forest for the trees,” Barkan explains. “The advice we give is not anchored in the choice we would make. When we give advice, we don’t consider what we would have done in the same situation. Instead, our role as adviser distances us from the dilemma at hand.

From afar, we see the forest. We consider long-term goals that are worthy and desirable. As advisers, we overlook the trees and discount obstacles and impediments on the way to this goal. As choosers, however, we can’t avoid seeing the trees – sometimes to the extent of losing the forest. As choosers, our mindset is oriented toward implementation and we give more weight to concrete details of feasibility and pragmatism.

They conducted a series of six studies showing that – compared with choosers – advisers weigh idealistic considerations more heavily than pragmatic ones, place greater emphasis on goals (“why?” questions) than on means to achieve the goals (“how?” questions) and generate more reasons in favor of acting idealistically. Advisers do not put themselves in the chooser’s position before offering advice (unless specifically asked to). Finally, studies confirmed that choice-advice difference was present in consequential reallife decisions.

“The clash between the idealistic desire to follow our dreams and the pragmatic considerations that hold us back resembles the experience you go through looking at the famous picture of the young/old woman. You see the young woman for a moment, but then the old lady jumps in,” says Barkan. “You can’t keep a steady image of one of them for very long, and you can’t see both of them at the same time.”

Then how can people follow their dreams? One answer lies in the findings, Barkan says: “It takes two. Not one person juggling two hats, but actually two people – a believer and a doer. They may fight throughout the journey, but if they share a dream they have a better chance of making it a reality together than apart.”