Most strokes occur when a blood clot lodges in a blood vessel that leads to the brain, resulting in weakness or paralysis and sensory, cognitive, and speech impairments. It is the second leading cause of death worldwide and the fourth leading cause of death in the United States.
More than 795,000 Americans suffer a stroke each year, with more than 129,000 fatalities. Of the survivors, 20 to 40 percent are still unable to care for themselves independently after one year, making stroke a leading cause of disability. This costs the United States more than $70 billion per year.
And yet, there are relatively few treatment options for stroke survivors. Stroke patients can receive injections of a medication called tissue plasminogen activator (tPA), which can help protect the brain against damage if administered within a few hours of a stroke. However, some estimates have found that tPA benefits fewer than 5 percent of patients, typically because the damage has already been done by the time the patients get to a hospital.
But now, in a new study published in Proceedings of the National Academy of Sciences, scientists have invented a way to stimulate the brain to regrow damaged areas a full five days after a stroke occurs.
Shining a Light into Dark Places
The research team, led by Michelle Cheng, a research associate in the department of neurosurgery at the Stanford University School of Medicine and first author on the study, wanted to test the theory that stimulating the brain can help it regrow neural connections after it’s been damaged. However, Cheng wanted to stimulate very specific brain areas, which is difficult to do through the skull. So, she tried a new technique called optogenetics.
This involves genetically engineering mice to express a certain light-sensitive protein, called rhodopsin, in the nerve cells of the targeted brain region. In this case, researchers focused on the motor cortex, which is responsible for movement, balance, strength, and other physical activities. Then, Cheng implanted the mice with a tiny fiber optic blue laser wire. When she turned on the light, the light-sensitive proteins caused the brain's nerve cells to fire in very specific patterns.
Cheng induced a stroke in the mice, then used the light to stimulate the mice’s brains in patterns that resembled normal activity. After two weeks, the mice who received the treatment showed huge improvements. They gained weight, experienced increased blood flow in the stimulated brain areas, and saw increased production of BDNF and NGF, two chemicals that cause the brain to grow new and stronger connections.
“We believe the stimulation was able to activate alternative brain circuits involved in motor function that were not damaged by the stroke,” said study co-author Gary Steinberg, chair of the department of neurosurgery at Stanford, in an interview with Healthline. “Interestingly, the largest changes in [brain chemicals] and growth factors were found in the [opposite side’s] cortex, suggesting the other side of the brain is compensating for the stroked circuits.”
The researchers only observed benefits in mice that had experienced a stroke. Unaffected mice didn’t show any gains from the stimulation. “We believe the stroke environment is necessary for the stimulations to produce more [brain chemicals] and growth factors,” explained Steinberg. “It may be that the stroke primes certain surviving neurons in other areas to respond to the stimulation.”
Nerve growth isn’t always a good thing — for example, nerve overgrowth has been linked to problems like seizures. Fortunately, that wasn't the case for Steinberg and his team. He said, “We didn't observe any seizures, nerve overgrowth or other adverse effects in our study, but further work will have to clarify this issue."
Hope for the Future
Although optogenetics isn’t ready for human trials, Steinberg is hopeful that it might enter testing within three to five years. Humans can’t be genetically engineered to express rhodopsins from birth like mice can, but instead, doctors can inject a gene-bearing virus to modify cells’ DNA to carry the rhodopsin-expressing genes.
Steinberg also points out that we don’t have to wait for optogenetic technology to mature in order to begin experimenting with his findings in humans. “Electrical stimulation using a small implanted electrode in the human brain is already in widespread use for treating Parkinson's disease and chronic pain, and a surface electrode grid approved for epilepsy, so it would be very straightforward to use the same techniques for treating stroke patients,” he said.
Either way, the team's work represents a major step forward for stroke treatment. Steinberg said, “If this stimulation therapy works in humans it would represent a major advance in improving the quality of life for stroke victims.”