Published online August 18th, a recent study form the Stanford University School of Medicine holds great promise for recovery from strokes in the absence of early intervention.
Claiming 15 million new victims per year across the globe, stroke is recognized as the second- largest cause of death, according to Gary Steinber, MD, PhD, professor and chair of neurosurgery at the school and senior author of the study. In the U.S. alone, stroke accounts for about 800,000 new cases annually, exacting a tab near $75 billion in medical costs and lost productivity.
Although an injectable medication knows as tPA (tissue plasminogen activator) may limit stroke damage, it must be infused within hours of the event. When most patients arrive at medical centers, this critical window of opportunity has usually transpired and no more than 5% of patients actually benefit from it. Perhaps more disturbingly no pharmacological therapy has been shown to enhance recovery from that point on.
Applying light-driven stimulation (Optogenetics) directly to the brain nerve cells of mice who had suffered strokes days earlier, Dr. Steinberger and his colleagues discovered that they showed remarkably greater recovery in motor ability than their counterparts without stimulation. Moreover, the treatments promoted recovery even when initiated up to five days after the stroke.
“In this study, we found that direct stimulation of a particular set of nerve cells in the brain — nerve cells in the motor cortex — was able to substantially enhance recovery,” said Steinberg, a Bernard and Ronni Lacroute-William Randolph Hearst Professor in Neurosurgery and Neurosciences.
He goes on to explain that the nature of seven of every eight strokes destroys tissue and that some degree of recovery is always possible but rarely complete, typically all but ceasing three months after a stroke.
Previous animal studies using electrical stimulation of the brain also resulted in improved stroke recovery but was problematic in its over-broad application to all cell types in the stimulation area, complicating analysis and producing unwanted side effects.
Optogenetics is a technology pioneered by the study’s co-author, Karl Deisseroth, MD, PhD, professor of psychiatry and behavioral sciences and bio-engineering. By exposing light-sensitive protein in specifically targeted brain cells to the right wavelength, the protein is activated,
causing the cell to fire. Using an implanted optical fiber, Steinberg’s team selectively expressed protein in the primary motor cortex near the stroke site and then monitored biochemical changes and blood flow there. “We wanted to find out whether activating these nerves cells alone can contribute to recovery”, Steinberg said.
A test of the mice two weeks later appears to provide a resounding yes. Optogenetically stimulated mice performed significantly better than their un-stimulated counterparts in motor coordination, balance and strength.
Moreover, the stimulated group regained substantially more weight and enjoyed enhanced blood flow in their brain. Perhaps most encouraging, substances in their brain called growth factors were far more numerous and they showed increased levels of proteins that allow nerve cells to alter their structure in response to experience – such as practice or learning.
Stimulating the brain optogenetically joins a long list of other treatments such as electroconvulsive therapy that use electricity, magnets, or implants to directly touch or activate the brain. DBS (deep brain stimulation), also known as a ‘brain pacemaker’ has shown great promise in addressing diseases ranging from Parkinson’s to depression. Despite long use, however, it is not largely understood.
Optogentically altering the brain, however, provides a wealth of information about how exactly its mechanism works and how proteins in the brain react and behave. While the long term effects are yet unknown, this method has the potential to dramatically improve the lives of millions of stroke victims.