Electric Current Helps Stroke Recovery

Stanford Medicine researchers have discovered that a brain implant that delivers and electrically stimulates transplanted stem cells and stimulates injured brain tissue after a stroke promotes recovery in mice

Worldwide, more than 10 million strokes occur each year, and at least half of them suffer from life-changing disabilities

Although hundreds of studies in animals -- and a handful in humans -- have shown that transplanting stem cells into the brain can improve stroke outcomes, the challenge is finding the best way to deliver and use these cells

Now, researchers at Stanford School of Medicine have developed a tool that addresses both of these problems

The device is a tiny conductive polymer implant 1mm wide and 3mm long, about a quarter the thickness of a credit card

"Conducting polymers have all the advantages of polymers," said Paul George, MD, assistant professor of neurology and neuroscience

Not only did this conductive polymer system work as intended, it also helped rodents recover faster and better after a stroke

"We found that if we electrically modulate transplanted human stem cells in a rodent stroke model, we can almost double the therapeutic effect of the stem cells themselves," said George

The conducting polymer system is described in a paper published March 15 in Nature Communications

brain boost

George's team started by looking at how the body uses electrical signals to generate its own stem cells

Once they developed a tool that could do this, the team tested it on mice that had experienced a stroke

Some mice received stem cell transplants

As expected, animals that received stem cells combined with electrical stimulation experienced earlier and longer-lasting recovery than the other groups

However, these benefits do not appear to come entirely from stem cells

"We're trying to understand the correct stimulation patterns and how to manipulate the system to see if we can further optimize the body's own repair mechanisms -- how to make the process more efficient," George said

The role of STC2

George's team also wants to figure out how nerve regeneration works
.
They found that electrical stimulation altered the brain's repair mechanisms and profoundly altered gene expression in stem cells
.
They found nearly 600 up-regulated genes and 168 down-regulated genes in the transplanted cells
.
Genes that were up-regulated increased their response to extracellular signals, while genes that were down-regulated decreased this response
.
One of the most up-regulated genes commands the production of stanniocalcin 2 (STC2), a protein involved in cell growth
.

When the scientists used a virus to reduce STC2 levels in the transplanted stem cells, the positive effects of electrical stimulation disappeared and healing stopped
.
When they injected the animals directly with STC2, their brains produced more stem cells, leading to better outcomes
.
George said research is needed to figure out how and why increasing STC2 causes the brain to produce more stem cells
.

The human brain loses some of its elasticity over time
.
Although it can still generate new stem cells throughout life, the number decreases with age
.
Stroke exacerbates this decline
.
Because strokes often affect older adults, devices like conductive polymers could improve the brain's ability to heal at a critical time in the recovery process
.

"In our rodent model, the brain got 20 percent better on its own after a stroke," George said
.
"Other groups that have used stem cells have achieved recovery rates of 50 to 60 percent
.
Our recovery rates are 80 to 90 percent.
%
.
This has important therapeutic considerations for the numerous completed and ongoing clinical stem cell trials, and may be a new avenue to optimize this treatment approach
.
"