For release: Wednesday, July 12, 2006
Research funded in part by the National Institute of Neurological Disorders and Stroke (NINDS) shows that mice with a brain injury similar to that of many premature babies can generate new neurons that help to repair the damage. The study is the first to show that substantial recovery from neonatal injury can occur in the developing brain. The finding helps to explain why many children born prematurely with very low birth weight are able to overcome their early difficulties.
“This study shows that the brain has intrinsic capacity to recover after injury. That is, the neuron is not lost forever – there are progenitor cells (specialized neural stem cells) that can react to an insult and then generate the proper type of cells that lead to cognitive improvement,” says lead investigator Flora Vaccarino, M.D. of Yale University School of Medicine in New Haven, Connecticut. The study appears in the May 2006 issue of Experimental Neurology*.
Children born prematurely with very low birth weight have an increased risk of problems ranging from attention deficit hyperactivity disorder to cerebral palsy or mental retardation. However, previous research by coauthor Dr. Laura Ment, also of Yale, has shown that most preterm very low birth weight infants improve significantly on tests of cognitive function during early childhood and eventually can reach normal range on tests of verbal comprehension and intelligence by age 8. Recent reports show that 2/3 of preterm infants require no special assistance in school by the ages of 14 to15. This suggests an improvement and a plasticity that leads to changes in cognitive function in those born prematurely.
“While preterm birth can result in significant disability, there is evidence for the improvement in function over time. The study by Dr. Vaccarino can help to highlight why this change happens in the brain,” says Dr. Ment. “Also, if we can understand how the young brain can recover from injury, we can also gain some insight into why, in some unfortunate instances, this recovery doesn’t happen.”
In their study, the researchers used an animal model to study adaptive changes in the developing brain after injury. Dr. Vaccarino and her colleagues have developed a neonatal mouse model of oxygen deprivation that mimics most of the problems of preterm infants. The animal model has an injury very similar to that of infants born prematurely with hypoxia, which is a reduction in the amount of oxygen passing into the blood that often results from being born with immature lungs.
“This is a powerful model because the behavioral and physiological effects in the infant mouse brain are very similar to those in preterm children including the subtle atrophy in brain weight, brain volume, and loss of cortical neurons immediately after the chronic hypoxia treatment. The behavioral effects of hyperactivity and cognitive disturbances are also found in the experimental mice,” Dr. Vaccarino says.
The investigation found that the loss in brain weight, cortical volume, and cortical neuron number all recovered one week after the hypoxia ended. Also, the recovered brain areas that had been exposed to hypoxia had increased numbers of newly generated neurons as compared to control brains. The data indicates these newly generated neurons result from neurogenesis and suggests that the developing brain has the ability to recover from or compensate for early injury. This could mean that the damage suffered when premature infants lack sufficient oxygen because of either lung diseases of prematurity or apneic spells (periods where they stop breathing) may be reversible. This recovery may not be possible for all brain injuries, however. The severity of the damage and a possible critical period or window of opportunity may affect the brains’ ability to repair itself.
The next steps in the research will be to identify the category of the newly generated cells and to establish how these news cells interact with the older or pre-existing neurons. The researchers must also determine if the new generation of cells is actually beneficial and if it is directly involved in promoting the recovery seen in the behavior of both mice and humans. Evidence that the cerebral cortex can repair itself by making new neurons will contribute significantly to the understanding of brain development in premature infants who are at risk for postnatal brain injury.
The NINDS is a component of the National Institutes of Health within the Department of Health and Human Services and is the nation’s primary supporter of biomedical research on the brain and nervous system. The National Institutes of Health (NIH) is comprised of 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary Federal agency for conducting and supporting basic, clinical, and translational medical research, and investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.
*Fagel DM, Ganat Y, Silbereis J, Ebbitt T, Stewart W, Zhang H, Ment LR and Vaccarino FM. “Cortical Neurogensis Enhanced by Chronic Perinatal Hypoxia” Experimental Neurology, May 2006, Vol. 199, pp. 77 - 91.
-By Michelle D. Jones-London, Ph.D.
Last Modified January 31, 2007