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Thread: UCLA Neuroscientists First To Show That Adult Brains Turn Back Developmental Clock To Repair Damage

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    UCLA Neuroscientists First To Show That Adult Brains Turn Back Developmental Clock To Repair Damage

    UCLA Neuroscientists First To Show That Adult Brains Turn Back Developmental Clock To Repair Damage
    A new study by UCLA neuroscientists shows for the first time that a unique pattern of cellular activity found in early brain development also triggers repairs to damaged adult brains. The findings, appearing in the July 15 edition of the peer-reviewed Journal of Neuroscience, hold implications for treating brain damage caused by stroke and other disorders.
    Researchers in the Department of Neurology and Brain Research Institute at UCLA used rat models to show how cells in brains damaged with stroke-like lesions, caused by interruption of blood flow, develop slow synchronous activity. This activity triggers cells to sprout new connections into areas of the brain disconnected by the lesion.

    "Our research shows for the first time that this activity works to trigger repairs in adult brains," said Dr. Marie-Francoise Chesselet, professor of neurology at the David Geffen School of Medicine at UCLA and study co-author. "Previously this activity has been identified as a key component of brain development."

    Scientists and clinicians had recognized this pattern of activity for many years after brain injury in humans, but its function remained unknown. This new research suggests that these cellular rhythms may be signaling a repair process in the human brain after injury.

    "On its own, a damaged brain has a limited ability to repair itself. Recovery is partial," said Dr. S. Thomas Carmichael, assistant professor of neurology at UCLA and study co-author. "A better understanding of how the brain recovers from injury will allow us to manipulate the repair process and to maximize recovery from brain damage caused by stroke and other disorders."

    The researchers made their discovery using a model of brain injury that allowed them to isolate signals specific to the sprouting of new connections from other changes that occur because of damage. They then measured the frequency, power and synchroneity of brain activity in a model that induced sprouting and compared to another that did not. The researchers also found that blocking the brain rhythms blocked sprouting as well.



    The research was supported by a Howard Hughes Medical Institute Post-Doctoral Research Fellowship for Physicians, held by Carmichael at the time of the study, and by a National Institutes of Health grant.



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    Brain Turns Back Developmental Clock for Repairs
    Wed Jul 17, 2:20 PM ET
    By Melissa Schorr

    NEW YORK (Reuters Health) - After an injury, the brain produces synchronized electrical pulses that appear to act as a signal to generate new nerve connections, according to a team of researchers who made the discovery while studying the brains of rats.



    Such signals--which are normally seen in early brain development--have been observed for years after brain injuries, but their function has been unclear.

    "This activity plays a role in triggering the rewiring of the brain," senior author Dr. Marie-Francoise Chesselet, a professor of neurology at the David Geffen School of Medicine at the University of California, Los Angeles (UCLA) told Reuters Health.

    Contrary to earlier beliefs, scientists are coming to find that parts of the brain do have the ability to rewire themselves after an injury, even over long distances of the cortex. However, the mechanism of how the brain knows to begin the repair work is not clear.

    The team of UCLA researchers has shown previously that this rewiring only occurs in response to certain forms of injury: Rat brains were able to form new nerve connections if the lesion occurred as a result of decreased blood flow and oxygen loss, as in a stroke, but not if the brain damage was caused by aspiration, or being sucked out.

    To investigate what special mechanisms occur in response to a loss of blood flow, Dr. S. Thomas Carmichael and colleagues gave rats stroke-like lesions using both methods and tracked the brain cells' response for 7 days. The results are published in the July 15th issue of Journal of Neuroscience.

    The investigators found that for a few days after brain injuries due to reduced blood flow, the neurons began firing in a slow, low-frequency, synchronous pattern, rather than their normal independent and fast rhythm pattern. At the same time, damaged nerves sprouted new axons, a long extension of the nerve cell that conducts electrical impulses away from the cell's central core. What's more, blocking the synchronous nerve cell firing appeared to block the nerve cell growth as well.

    Rats that had developed lesions as a result of aspiration did not show this form of nerve growth or neuronal activity.

    This form of nerve cell activity has been observed in stroke victims, but its function was not understood, Chesselet noted.

    The researchers theorize this form of neuronal activity, a similar form of which takes place during early brain development, may be a signal to distant brain cells to begin the rewiring process.

    "It seems in this situation, the brain uses again a mechanism it has used in development," she noted.

    Chesselet said ideally, doctors could someday learn to stimulate this type of neuronal activity to induce brain recovery among stroke victims. If this stimulation proves to be crucial, doctors should also avoid disturbing its natural occurrence during the use of various therapies that aim to prevent cellular death among stroke victims.

    "We need to be careful to not block this activity in people," she said. "You could have therapy that prevents cell death, but if it blocks this activity, it may do more harm than good."

    SOURCE: Journal of Neuroscience 2002;22:6062-6070.

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