Report in Mice
Investigator: Peter Riess

Spinal Stem-Cell Transplants Aid Coordination
Mari N. Jensen

In one of the first studies testing whether stem cells can reverse the effects of traumatic brain injury, researchers show that injecting stem cells near the site of injury helps restore the mobility of brain-injured mice.

Traumatic Brain Injuries (TBI) -- like those caused when a person's head hits a car windshield during an accident -- are a leading cause of chronic disabilities. So trauma surgeon and researcher Peter Riess of the University of Pennsylvania in Philadelphia and his colleagues tested whether neural stem cells could aid recovery and whether such cells, once transplanted, would migrate to the injured part of the brain.

The team injured the cerebral cortex of 58 mice in a standardized fashion by cutting a hole in their skulls and then slamming a 3-mm-wide piston into their brains. Three days afterwards, half the mice received one of two experimental treatments: an injection of mouse cerebellar stem cells ( clone C17.2) next to the injury or the same type of injection on the opposite side of the brain. The other half of the mice served as controls and got an injection of Human Embryonic Kidney (HEK) cells either near the injury or on the opposite side of the brain. Then the mice were given weekly tests to assess the animals' locomotion, balance, coordination, and learning abilities.

In one test known as the rotarod test, mice walk on a rotating cylinder as it speeds up - similar to walking on a mouse exercise wheel, but on the outside. The other test is like a lumberjack logrolling contest: to reach their cages, the animals must traverse a meter-long pole that rotates. In these tests of coordination and balance, uninjured animals did fine, but injured animals tended to slip off. Although all the injured mice improved somewhat over the course of the 12-week experiment, those who got neural stem cell transplants improved more. Animals whose injections were near the site of injury improved the most.

However, the neural stem cell treatment didn't have much effect on the animals' learning ability. In a test called the Morris Water Maze, mice are put into a little swimming pool that has markings around the walls and a hidden underwater platform somewhere. Normal animals, after swimming around a bit, find the platform. Apparently they note its location, because the next time they're plopped in the pond they swim right to it. The brain-injured animals, regardless of what kind of treatment they had, took a lot longer to learn the platform's location.

Although balance, locomotion and cognition are all affected by TBI, most research investigates just one of those components. "It's a nice comprehensive set of analyses," says neurosurgeon David Hovda of the University of California in Los Angeles. Says Reiss: "The big deal is, it seems to work."