Article found on Science Daily
Every year in the United States, nearly two million Americans sustain a traumatic brain injury (TBI). Survivors can live with lifelong physical, cognitive and emotional disabilities. Currently, there are no treatments.
One of the biggest challenges for neuroscientists has been to fully understand how a TBI alters the cross-talk between different cells and brain regions.
In the new study, researchers improved upon a process called iDISCO, which uses solvents to make biological samples transparent. The process leaves behind a fully intact brain that can be illuminated with lasers and imaged in 3D with specialized microscopes.
The researchers focused on connections to inhibitory neurons, because these neurons are extremely vulnerable to dying after a brain injury. The team first looked at the hippocampus, a brain region responsible for learning and memory. Then, they investigated the prefrontal cortex, a brain region that works together with hippocampus. In both cases, the imaging showed that inhibitory neurons gain many more connections from neighboring nerve cells after TBI, but they become disconnected from the rest of the brain.
To get a closer look at the damaged brain connections, the research team devised a technique for reversing the clearing procedure and probing the brain with traditional anatomical approaches.
The findings surprisingly showed that the long projections of distant nerve cells were still present in the damaged brain, but they no longer formed connections with inhibitory neurons.
The researchers then wanted to determine if it was possible for inhibitory neurons to be reconnected with distant brain regions. To find out, the research team transplanted new interneurons into the damaged hippocampus and mapped their connections, based on the team’s earlier research demonstrating interneuron transplantation can improve memory and stop seizures in mice with TBI.
The new neurons received appropriate connections from all over the brain. While this may mean it could be possible to entice the injured brain to repair these lost connections on its own, the researcher said learning how transplanted interneurons integrate into damaged brain circuits is essential for any future attempt to use these cells for brain repair.
“Our study is a very important addition to our understanding of how inhibitory progenitors can one day be used therapeutically for the treatment of TBI, epilepsy or other brain disorders,” said the researcher.