Researchers identify molecular cascade that drives sprouting in brain after stroke

November 13, 2017

Secondly, the molecular program that controls the formation of new connections in the brain after stroke differs considerably between aged and young adults. "Stroke, of course, usually happens to the elderly," he said. "These differences may explain in part why recovery is diminished in aged individuals; they respond to stroke with a very different genetic program of recovery." And there was a more intriguing discovery: In the aged brain, neurons that sprout new connections not only activate genes to induce these new connections, they simultaneously activate genes that slow down or collapse these new connections. "It's as if you are accelerating a car while at the same time hitting the brakes," he said. "This response of aged brain cells may show why the aged brain does not respond and recover after stroke like the young adult's."

Finally, the researchers developed a new method of drug delivery in the brain after stroke to test the role of specific molecules in the sprouting transcriptome. After stroke, the area of damage gets absorbed and becomes a cavity. This cavity sits right next to the "peri-infarct tissue," the part of the brain that is sprouting new connections and recovering. "We developed a way to fill the cavity with a natural biological material that releases brain repair drugs slowly over time directly to this peri-infarct tissue," said Carmichael. The researchers added normal brain proteins to a sponge-like biopolymer hydrogel, which slowly released the neural repair agents. This promoted axonal sprouting in the brain after stroke. "This approach takes advantage of now-standard human neurosurgical approaches, in which injections can be targeted precisely to brain structures," he said.

This research into stroke closely follows other research published by Carmichael last week in the journal Nature. That study showed another factor in the brain that limits recovery after stroke. Carmichael and colleagues found that stroke causes the brain to over-activate inhibitory signaling, causing the brain to be hypo-excitable. The UCLA team determined what molecules led to this increased brain inhibition after stroke, reversed the inhibitory signaling and enhanced recovery of function. The research also identified a promising drug therapy to help reverse the damaging effects of stroke.

Source: University of California - Los Angeles