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Thread: Molecule Rewires Brain After Stroke/Body Substance Helps Nerves Reconnect Post-Stroke

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    Senior Member Max's Avatar
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    Molecule Rewires Brain After Stroke/Body Substance Helps Nerves Reconnect Post-Stroke

    Molecule Rewires Brain After Stroke
    Mon Jun 24, 5:12 PM ET
    By Adam Marcus
    HealthScoutNews Reporter

    MONDAY, June 24 (HealthScoutNews) -- A natural molecule found in food and over-the-counter supplements may be the first drug that can help the nervous system rewire itself in the aftermath of a stroke or other brain damage.


    When infused into rat brains, the compound, called inosine, spurs the growth of healthy neurons to bypass dead spots left in the wake of surgically induced brain attacks, a new study says. These fibers, which restore missing electrical impulses necessary for proper movement and other functions, help the animals regain at least some lost performance on a variety of behavior tests.

    "What inosine is doing is getting fibers on the good side of the brain to form new connections to the spinal cord," says Larry Benowitz, a Harvard University neuroscientist and a co-author of the study. "These guys aren't going to be able to play a piano concerto, but they might be able to swipe at something or retrieve food that that they'd not been able to before."

    Existing stroke therapies try to prevent additional damage after episodes of blood loss to a region of the brain. "But they don't have any effect on stimulating the intact brain to form new connections," Benowitz says.

    The research was funded in part by Boston Life Sciences, a biotech company that hopes to bring inosine therapy to human stroke patients. The company is now planning a study testing the drug in people, and with regulatory approval will begin the trial early next year.

    Dr. Mark Lanser, the company's chief scientific officer, says the substance must now be administered as an infusion directly into the brain because it is quickly broken down in blood and by the gastric system. It's also too big to penetrate the blood-brain barrier that protects the organ from large molecules.

    However, Lanser says that if clinical studies show promise, the firm would try to develop a version of inosine that can be taken orally or by injection. Boston Life Sciences would also like to test the compound in patients with spinal cord injuries and head trauma.

    An estimated 750,000 Americans suffer strokes each year, and 160,000 die from them. The debilitating events occur when blood flow to the brain is interrupted, either by a ruptured or blocked blood vessel.

    Inosine is a precursor to adenosine, a key player in a variety of body functions, from the creation of DNA molecules to the generation of energy. The chemical, found in brewer's yeast and organ meats like liver and kidney, has been touted as an exercise aid, though its record as a performance enhancer has fallen flat.

    Still, the new work, published in tomorrow's issue of the Proceedings of the National Academy of Sciences ( news - web sites), suggests a more important agenda for the chemical.

    In earlier findings a team led by Benowitz, who heads a research lab at Children's Hospital Boston, showed that inosine prompts animal neurons in a dish to extend their axons. Axons are the long tendrils that link brain cells. How this works isn't entirely clear, but the substance seems to switch on genes that go dormant in adult animals, he says.

    This time, Benowitz's group sought to learn what happens to brain cells bathed in inosine after surgical strokes that kill off many millions of neurons.

    The researchers performed the operation on two groups of rats, leaving them severely impaired.

    Within about three weeks of the stroke-inducing procedure, untreated rodents showed a 50 percent improvement in one standard test of mobility that measures paw reaching.

    However, during the same period the animals that received continuous inosine infusions regained nearly complete function on the test. They also made impressive strides on other exams that included swimming and grasping for food.

    Treated animals began outperforming the untreated rats by the seventh day of testing, and progressively gained ground on them throughout the study. However, it's not clear if the benefits increased with time or if those gains were simply the echo of a one-shot boost, Benowitz says. "More research will be needed to establish the optimal procedures for treatment," he adds.

    Whatever the case, tissue samples taken at the end of the performance studies showed that the treated animals had substantially more spreading of axons into parts of the brain deprived of their usual connections.

    Benowitz says it's difficult to quantify the difference, though it appears to be three to five times as much axon growth as in the untreated rodents. While that constitutes only a small fraction of the original hookups, it's enough to spark the improvements in behavior.

    Results his group obtained in recent weeks show treatment must also start within a day of a stroke to be effective. Why is something of a mystery, Benowitz says, because the compound acts not on the organ's deadened region but on the remaining healthy neurons.

    Dr. Lawrence M. Brass, a neurologist at Yale University School of Medicine and a spokesman for the National Stroke Association, says the work could make a "huge impact on reducing the burden of stroke on patients and on society."

    Brass said inosine "really represents a different approach than we've been using for the last couple of years," and reflects a shift in thinking about the brain.

    As a medical student, Brass says, he was taught that the brain's major wiring is set at birth. However, as this study and previous work reveal, the brain sprouts new cells throughout its life, and those cells can form meaningful connections with other neurons.

    "It's not just new wires that grow from [and to] nowhere. That's what is really exciting," he says.

    What To Do

    To learn more about inosine, try BlueCross. For more on strokes, visit the National Stroke Association.

    [This message was edited by Max on Jun 24, 2002 at 07:30 PM.]

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    Senior Member Max's Avatar
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    Body Substance Helps Nerves Reconnect Post-Stroke

    Body Substance Helps Nerves Reconnect Post-Stroke
    Mon Jun 24, 6:33 PM ET
    By Alison McCook

    NEW YORK (Reuters Health) - Injecting a substance found naturally in the body into the brains of rats helps restore some of the wiring between brain cells damaged by stroke, new research shows.


    In the study, Dr. Larry Benowitz of Harvard University and his colleagues injected inosine--a chemical used to help form adenosine (one of the compounds that make up DNA)--into the brains of rats who had suffered stroke.

    After an injection of inosine, rats improved their performance of certain movements, such as reaching for food or placing their paws on a table. Furthermore, analyses of the rats' brains showed that some nerve cells had, indeed, formed new connections to brain areas that had become isolated as a result of the stroke.

    Benowitz told Reuters Health that rats improved following injections of inosine, but that the drug could not totally reverse the effects of the stroke.

    The rats "are regaining a significant amount of function back that was lost," Benowitz said. "But no, it's certainly not complete."

    However, he added, people who suffer a stroke often experience severe impairment as a result. So even if inosine can not get them back into piano-playing shape, the drug may help them to lift their own forks or perform other functions of daily living they have lost.

    "So in terms of quality of life, a little bit of rewiring could go a long way," Benowitz said.

    Reporting in the June 25 issue of Proceedings of the National Academy of Sciences ( news - web sites), Benowitz and his team followed the progress of rats that had been given injections of inosine, and compared them to rats that did not receive the drug.

    Before the inosine kicked in, rats were barely able to place the forepaw that was affected by the stroke onto a table, the authors report. Nineteen days after the rats had received inosine, they had almost completely recovered the paw-placing abilities they had before the stroke. Rats that did not receive the drug had about a 50% improvement.

    In addition, inosine-treated rats eventually became better able than non-treated rats to reach for food, and they were better swimmers.

    About 750,000 people suffer a stroke each year in the US. Stroke damages parts of the brain by depriving those areas of oxygen from the blood. However, Benowitz explained, when certain regions of the brain are lost, that also affects other healthy brain areas that were receiving signals from the now-damaged cells.

    Inosine helps restore the connection of cells that have lost their signals to still-healthy regions of the brain by stimulating normal, undamaged cells to extend themselves towards the areas that have become isolated by stroke, the researcher explained.

    This "rewiring," in turn, helps restore some of the movements lost in rats following their strokes, Benowitz added.

    Because inosine occurs naturally in the body, it is unlikely to cause severe side effects, he said. As a worst-case scenario, he said that the drug might cause nerve cells to grow new connections where they are not needed, but all research up to now has not shown any evidence that this is occurring. However, further studies are needed to determine what other mood or behavioral effects the drug could have on people who receive it, the researcher added.

    SOURCE: Proceedings of the National Academy of Sciences 2002;99:9031

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    Senior Member DA's Avatar
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    cbs today ran a story on this.
    nothing new.

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