From: Andy Soos, ENN
Published January 15, 2010 11:37 AM

Rats, Humans and Strokes

A stroke (sometimes called an acute cerebrovascular attack) is the rapidly developing loss of brain function(s) due to a disturbance or loss in the blood supply to the brain. As a result, the affected area of the brain is unable to function, leading to inability to move one or more limbs on one side of the body, inability to understand or formulate speech, or inability to see one side of the visual field.

Two new studies by University of California (UC) Irvine biologists have found that a protein naturally occurring in humans restores motor function in rats after a stroke. Administered directly to the brain, the protein restores 99 percent of lost movement; if it's given through the nose, 70 percent of lost movement is regained. Untreated rats improve by only 30 percent.

"No drugs exist that will help a stroke after a few days. If you have a stroke, you don't have many treatment options," said James Fallon, psychiatry & human behavior professor and senior coauthor of the studies. "Now we have evidence there may be therapies that can repair damage to a significant degree long after the stroke. It's a completely unexpected and remarkable finding, and it's worth trying in humans."

A stroke is typically treated with a clot buster drug and is usually combined with supportive care (speech and language therapy, physiotherapy and occupational therapy. Secondary prevention with antiplatelet drugs (aspirin and often dipyridamole), blood pressure control, and statins may also be used.

The UC studies, carried out by postdoctoral researcher Magda Guerra-Crespo, chronicle the success of a small protein called transforming growth factor alpha, which plays critical tissue-forming and developmental roles in humans from just after conception through birth and into old age.

"TGF alpha has been studied for two decades in other organ systems but never before has been shown to reverse the symptoms of a stroke." Guerra-Crespo said. No lasting side effects were observed in the conducted studies.

In an earlier study scientists sought to learn whether TGF alpha administered directly to the brain could help rats with a stroke induced loss of limb function, typically on one side, as is seen in humans.

When put inside a cylinder, healthy rats will jump up with both front legs, but stroke impaired rats will use just one leg, favoring the injured side. When given a choice of directions to walk, impaired rats will move toward their good side which is an easily observed symptom.

One month after the study began rats suffered an induced stroke; some rats were then injected with TGF alpha. Within a month, they had regained their motor function. Rats that did not receive treatment improved just 30 percent.

Scientists examined the rats' brains and found that TGF alpha was stimulating neuron growth. First, it prompted adult stem cells in the brain to divide, creating more cells. Those cells then turned into brain cells and moved to the injured part of the brain, replacing neurons lost to the stroke. These new neurons, the scientists believe, helped restore motor function.

In the newest study, appearing online January 11 in the Journal of Stroke & Cerebrovascular Diseases, scientists placed TGF alpha in the rats' noses, simulating a nasal spray. They used a slightly different chemical version of the protein to render it more stable on its journey to the brain. After a month, the injured rats had regained 70 percent of their function, indicating that the intranasal method works well.

TGF Alpha promises the potential for improved post stroke treatment and recovery. Whether the TGF Alpha will work as well in humans is to be determined.

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