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Scientists prevent cerebral palsy-like brain damage in mice
Date:11/2/2011

ributable to brain injury that stems from inadequate oxygen and blood flow to the brain before, during or soon after birth," says first author Philip Verghese, PhD, a postdoctoral research associate in Holtzman's laboratory. "We wanted to see if those injuries still occur in the presence of increased levels of Nmnat1."

The researchers evaluated the effects of oxygen and blood flow deprivation in normal mice and in mice genetically engineered to produce higher-than-normal levels of Nmnat1.

As early as six hours later, the mice with enhanced Nmnat1 had markedly less injury to the brain.

A week later, when the researchers measured the amount of tissue atrophy in the brain, they found that mice with high Nmnat1 had experienced far less damage to key brain structures like the hippocampus and cortex, which are known to be injured in cerebral palsy.

In a series of follow-up studies with collaborators Jeff Neil, MD, PhD, the Allen P. and Josephine B. Green Professor of Neurology, and Yo Sasaki, PhD, research assistant professor of genetics, the scientists were surprised at what they saw.

MRI scans of the brain showed that Nmnat1 might be even more protective than the first experiment suggested. In mice with boosted Nmnat1 levels, the scans revealed little to no brain damage.

Laboratory studies of the brain cells indicated that Nmnat1 prevents a particular form of cell death.

"There are two types of injury in the developing brain from inadequate oxygen and blood flow," Holtzman explains. "One is necrosis, where cells swell rapidly, burst and die; another is apoptosis, where the cells shrink and die. We found that Nmnat1 prevents necrosis."

Necrosis is believed to be responsible for killing brain cells in ischemic stroke in adults, which temporarily cuts off oxygen and blood flow to the brain. Dying cells flood the surrounding area with a glutamate, which can harm nearby cells. When researchers simul
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Contact: Michael C. Purdy
purdym@wustl.edu
314-286-0122
Washington University School of Medicine
Source:Eurekalert

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