Researchers have converted brain immune cells into neurons that replaced damaged neurons and restored function in mice affected by stroke. The next step will be to investigate whether the same results can be achieved using human brain cells, opening the door to treating stroke.
After stroke or other cerebrovascular diseases result in poor blood flow to the brain, neurons are either damaged or die, causing unique physical and psychological defects. Now, researchers at Kyushu University in Japan restored motor function in stroke-affected mice by converting microglia, the brain's main immune cells, into neurons.
Kenichi Nakajima, the study's corresponding author, said: "When we are cut or broken, our skin and bone cells can replicate, thus healing our bodies. But neurons in our brains do not regenerate easily, so the damage is often permanent. Therefore, we need to find new ways to house lost neurons."
The researchers knew from previous studies that microglia could be coaxed to develop into neurons in the brains of healthy mice. After a stroke, microglia, which are responsible for clearing damaged or dead brain cells, move toward the site of injury and replicate rapidly.
"Microglia are abundant and located exactly where we need them, so they are ideal targets for transformation," said Takashi Irie, first author of the study.
Researchers induced strokes in mice by temporarily blocking the right middle cerebral artery, a major blood vessel in the brain that is commonly associated with stroke in humans. After a week, the researchers observed impairments in motor function in the mice, with a significant decrease in neurons in the striatum, a region of the brain involved in decision-making, action planning and motor control.
They used lentiviruses - a subclass of retroviruses used as viral vectors - to insert DNA into microglia at the site of stroke damage. The DNA contains instructions for producing NeuroD1, a protein that induces neuronal switching. Over the next few weeks, these cells develop into neurons.
Three weeks after DNA implantation, the mice's motor function improved. By eight weeks, the newly induced neurons had successfully integrated into brain circuits. When the researchers removed the new neurons, the improvements in motor function disappeared, confirming that the new neurons directly contributed to the mice's recovery.
"These results are promising," Nakajima said. "The next step is to test whether NeuroD1 can also effectively convert human microglia into neurons and confirm that our method of inserting genes into microglia is safe."
Because the mice were treated in the acute phase after stroke, when microglia have migrated to the site of injury, the researchers next planned to see whether they could produce a recovery effect in the mice at a later stage.
The research was published in the Proceedings of the National Academy of Sciences (PNAS).