Factors inhibiting the brain's natural self-healing process identified

Aug 7 2005

Factors that inhibit the brain's natural self-healing process and that may offer new insights into how to prevent brain damage in premature babies have been identified by a team of researchers supported in part by the March of Dimes.

The research is published online in Nature Medicine.

Stephen A. Back, M.D., Ph.D., an Associate Professor of Pediatrics and Neurology at the Oregon Health & Science University School of Medicine, Portland, and colleagues identified some of the key factors that prevent brain damage repair in premature babies and patients with multiple sclerosis (MS) or certain other neurological diseases. Their findings offer important clues about why the nervous systems fails to repair itself and suggest that some forms of brain damage could be reversed.

Dr. Back, who studies developmental brain injury in premature infants, previously found a link between damage to white matter in the brain associated with premature birth, and damage to immature cells in the brain and spinal cord, called oligodendrocyte progenitors. These cells normally mature to become oligodendrocytes that make myelin (the insulating sheath surrounding nerve fibers in the brain and spinal cord) throughout life. In some cases, these cells fail to mature and cannot repair damage to the white matter of the brain.

The white matter is made up of long nerve fibers wrapped in myelin. Different kinds of white matter injury cause cerebral palsy and learning problems in children born prematurely, and MS in older children and adults. Dr. Back and his colleagues found that hyaluronic acid (HA) prevent immature oligodendrocytes from maturing and coating nerve fibers with new myelin. Astrocytes, the first-responders to nerve damage in the brain, produce HA, which accumulates on nerve fibers where myelin is missing.

"Preterm birth can interrupt the normal myelination process. Therefore, this report may help to explain the brain damage seen in premature babies, some of whom have cerebral palsy," said Michael Katz, M.D., Senior Vice President for Research and Global Programs at the March of Dimes, which is supporting Dr. Back. "Until we find the answers to preventing prematurity, research such as this may lead us to new ways to prevent brain damage and has the potential to improve the lives of thousands of infants."

Prematurity is the leading killer of America's newborns and has increased 29 percent since 1981. More than 470,000 babies are born prematurely each year in the United States. Premature babies often die or suffer lifelong consequences, including cerebral palsy, mental retardation, chronic lung disease, blindness, and hearing loss.

According to research conducted by the National Institute of Child Health and Human Development, 25 percent of extremely premature babies have neurological problems at 18 to 22 months, and 17 percent will develop cerebral palsy.

"Hyaluronan Accumulates in Demyelinated Lesions and Inhibits Oligodendrocyte Progenitor Maturation," published in the September 2005 issue of Nature Medicine, volume 11, number 9, was a collaborative effort of Dr. Back, senior researcher Larry Sherman, Ph.D., an Adjunct Associate Professor of Cell and Developmental Biology, OHSU School of Medicine, and other colleagues at OHSU, the National Institutes of Health, and the Cleveland Clinic Foundation.