Embryonic progenitor cells were transplanted into mice with traumatic brain injury that are capable of generating inhibitory interneurons, which are a specific type of nerve that control the activity of brain circuits, targeting the hippocampus region of the brain responsible for learning and memory.
The transplanted neurons were found to have migrated into the areas of injury where they had formed new connections with the injured brain cells which thrived long term. The animals displayed signs of memory improvement within a month of treatment, such as being able to distinguish the difference between a box where they had an unpleasant experience from a neutral box just as well as animals that never has a brain injury.
“Inhibitory neurons are critically involved in many aspects of memory, and they are extremely vulnerable to dying after a brain injury,” says Robert Hunt, an assistant professor of anatomy and neurobiology at the School of Medicine at the University of California, Irvine, who led the study. “While we cannot stop interneurons from dying, it was exciting to find that we can replace them and rebuild their circuits.”
“The idea to regrow neurons that die off after a brain injury is something that neuroscientists have been trying to do for a long time,” Hunt says. “But often, the transplanted cells don’t survive, or they aren’t able to migrate or develop into functional neurons.”
To test their findings the UCI researchers pharmaceutically silenced the transplanted neurons which caused the memory problems to return. In 2018, the same team used a similar approach which was delivered the same way to newborn mice that was observed to improve memory of those with a genetic disorder. There are no treatments available currently for those who have experienced a head injury, if these findings can be replicated in humans using interneurons created from human stem cells it could have a tremendous impact.
“It was exciting to see the animals’ memory problems come back after we silenced the transplanted cells, because it showed that the new neurons really were the reason for the memory improvement,” says first author Bingyao Zhu, a junior specialist.
“So far, nobody has been able to convincingly create the same types of interneurons from human pluripotent stem cells,” Hunt says. “But I think we’re close to being able to do this.”
