An experimental drug tested by UC San Francisco scientists completely reversed severe learning and memory impairments caused by traumatic brain injury (TBI) in mice and was effective even when administeed as much as a month after injury. The drug used in the new research, known as ISRIB (pronounced “iz-rib”), was discovered in 2013 and had previously been shown to enhance memory in normal mice. The drug was licensed in 2015 to Calico, a company involved in understanding the biology that controls the human lifespan. In the new research, scientists tested whether ISRIB could improve the ability to learn and form memories in mice with two different types of brain injury, each of which are known to degrade learning and memory in humans. Localized brain injuries called focal contusions can affect spatial memory, which helps both mice and humans navigate through the world and complete necessary everyday tasks. Concussive brain injuries can degrade working memory. To test ISRIB’s potential effects after focal injury, the researchers placed both normal and brain-injured mice in a “radial-arm water maze,” where their task was to learn the location of a platform hidden under milky water in one of eight arms of the maze. Normal mice improve steadily, eventually finding the platform quite quickly after being placed into the maze. Brain-injured mice, however, continue to make errors with no sign of improvement long after training. When brain-injured mice were given three injections of ISRIB beginning four weeks after injury, their performance in the maze was indistinguishable from that of normal mice, and the restoration of their ability to learn persisted for a week after the last injection. The drug’s effectiveness must undergo many more studies before it would be a candidate for clinical trials to treat brain-injured human patients.