Cerebral Palsy-Like Brain Damage In Mice

Researchers at Washington University School of Medicine in St. Louis have shown that protein can help prevent this type of brain damage that occurs in children with cerebral palsy.Using the mouse model that simulates the conditions that destroy the newborn, the researchers found that high levels of protective proteins, Nmnat1, substantially reduce the damage that occurs when the brain lacks oxygen and blood circulation. These findings are of potential new strategy for the treatment of cerebral palsy and stroke, and possibly Alzheimer's disease, Parkinson's disease and other neurodegenerative diseases. The research is reported online in the Proceedings of the National Academy of Sciences."Under normal circumstances the brain to process either a temporary interruption of blood flow or oxygen during birth, but when they occur together, and a long, long term disability and death may result," said lead author David M. Holtzman, MD, Andrew and Gretchen Jones professor and head of the department of neurology. "If we can use the same drugs induce protective pathways such as Nmnat1, it is possible to prevent brain damage that occurs due to this condition as well as neurodegenerative diseases."Researchers are not sure how Nmnat1 protects brain cells, but suspect that blocks the effects of the neurotransmitter glutamate is strong. Brain cells damaged by lack of oxygen or release of glutamate, which can overstimulate and kill neighboring nerve cells.Nmnat1 protective effect was first identified five years ago, Jeff Milbrandt, MD, PhD, James S. McDonnell Professor and Head of Genetics at Washington University, who suggests that the protein may prevent damage to peripheral nerves in the extremities of the body. Phillip Verghese, PhD, a postdoctoral researcher in the laboratory Holtzman wanted to see whether the protective effect of the protein extending into the brain."Cerebral palsy is sometimes caused by brain injury resulting from lack of oxygen and blood flow to the brain before, during or shortly after birth," said first author Philip Verghese, PhD, a postdoctoral researcher in the laboratory Holtzman. "We wanted to find out if their injuries are still occurring in the presence of elevated levels Nmnat1."Researchers evaluated the influence of oxygen and blood flow in normal mice and mice genetically modified to produce higher than normal levels Nmnat1.In the first six hours, mice with increased Nmnat1 less tangible damage to the brain.A week later, when scientists measured the amount of atrophy in brain tissue, they found that mice with high Nmnat1 suffered far less damage to key brain structures like the hippocampus and cerebral cortex, which is known injured cerebral palsy.In a series of advanced research with collaborators Jeff Neil, MD, PhD, Allen P. and Josephine B. Green Professor of Neurology and Yo Sasaki, Ph.D., assistant professor of genetics, scientists are surprised by what they see.MRI brain examination showed that Nmnat1 may be even greater protection than the first experiment suggested. In mice with increased levels Nmnat1, scans have revealed little or no brain damage.Laboratory studies of brain cells have shown that preventing Nmnat1 special form of cell death."There are two types of injury in the developing brain of oxygen and blood flow is insufficient," Holtzman said. "One of them is necrosis, where cells swell rapidly, explosion and die, another apoptosis in which cells shrink and die We have found that Nmnat1 prevent death .."Necrosis is believed responsible for killing brain cells in ischemic stroke in adults, which temporarily cut off oxygen and blood flow to the brain. Dead cells with glutamate floods the area, which can damage cells in the vicinity. When scientists simulate this process in vitro, brain cells die in the presence of fewer high Nmnat1.Scientists from Milbrandt and Holtzman laboratory for several possible explanations for the protective effect Nmnat1 it. Holtzman wants to test proteins in other models of brain injury and neurodegenerative diseases.