Featured Research

from universities, journals, and other organizations

Cerebral palsy-like brain damage prevented in mice

Date:
November 4, 2011
Source:
Washington University School of Medicine
Summary:
Scientists have shown that a protein may help prevent the kind of brain damage that occurs in babies with cerebral palsy.

Scientists at Washington University School of Medicine in St. Louis have shown that a protein may help prevent the kind of brain damage that occurs in babies with cerebral palsy.

Using a mouse model that mimics the devastating condition in newborns, the researchers found that high levels of the protective protein, Nmnat1, substantially reduce damage that develops when the brain is deprived of oxygen and blood flow. The finding offers a potential new strategy for treating cerebral palsy as well as strokes, and perhaps Alzheimer's, Parkinson's and other neurodegenerative diseases. The research is reported online in the Proceedings of the National Academy of Sciences.

"Under normal circumstances, the brain can handle a temporary disruption of either oxygen or blood flow during birth, but when they occur together and for long enough, long-term disability and death can result," says senior author David M. Holtzman, MD, the Andrew and Gretchen Jones Professor and head of the Department of Neurology. "If we can use drugs to trigger the same protective pathway as Nmnat1, it may be possible to prevent brain damage that occurs from these conditions as well as from neurodegenerative diseases."

The researchers aren't exactly sure how Nmnat1 protects brain cells, but they suspect that it blocks the effects of the powerful neurotransmitter glutamate. Brain cells that are damaged or oxygen-starved release glutamate, which can overstimulate and kill neighboring nerve cells.

The protective effects of Nmnat1 were first identified five years ago by Jeff Milbrandt, MD, PhD, the James S. McDonnell Professor and head of genetics at Washington University, who showed the protein can prevent damage to peripheral nerves in the body's extremities. Phillip Verghese, PhD, a postdoctoral research associate in Holtzman's laboratory, wanted to see if the protein's protective effects extend to the brain.

"Cerebral palsy is sometimes attributable to brain injury that stems from inadequate oxygen and blood flow to the brain before, during or soon after birth," Verghese says. "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 says. "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 glutamate, which can harm nearby cells. When researchers simulated this process in a test tube, fewer brain cells died in the presence of high Nmnat1.

Scientists in Milbrandt's and Holtzman's laboratories are following up on several potential explanations for Nmnat1's protective effects. Holtzman plans to test the protein in other models of brain injuries and neurodegenerative diseases.


Story Source:

The above story is based on materials provided by Washington University School of Medicine. The original article was written by Michael C. Purdy. Note: Materials may be edited for content and length.


Journal Reference:

  1. Verghese PB, Sasaki Y, Donghan Y, Stewart F, Sabar F, Finn MB, Wroge CM, Mennerick S, Neil JJ, MIlbrandt J, Holtzman DM. NAD-synthesizing enzyme nicotinamide mononucleotide adenylyl transferase 1 (Nmnat1) protects against acute neurodegeneration in developing CNS by inhibiting excitotoxic-necrotic cell death. Proceedings of the National Academy of Sciences, 2011; (in press)

Cite This Page:

Washington University School of Medicine. "Cerebral palsy-like brain damage prevented in mice." ScienceDaily. ScienceDaily, 4 November 2011. <www.sciencedaily.com/releases/2011/11/111102190404.htm>.
Washington University School of Medicine. (2011, November 4). Cerebral palsy-like brain damage prevented in mice. ScienceDaily. Retrieved July 29, 2014 from www.sciencedaily.com/releases/2011/11/111102190404.htm
Washington University School of Medicine. "Cerebral palsy-like brain damage prevented in mice." ScienceDaily. www.sciencedaily.com/releases/2011/11/111102190404.htm (accessed July 29, 2014).

Share This




More Mind & Brain News

Tuesday, July 29, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Losing Sleep Leaves You Vulnerable To 'False Memories'

Losing Sleep Leaves You Vulnerable To 'False Memories'

Newsy (July 27, 2014) A new study shows sleep deprivation can make it harder for people to remember specific details of an event. Video provided by Newsy
Powered by NewsLook.com
University Quiz Implies Atheists Are Smarter Than Christians

University Quiz Implies Atheists Are Smarter Than Christians

Newsy (July 25, 2014) An online quiz from a required course at Ohio State is making waves for suggesting atheists are inherently smarter than Christians. Video provided by Newsy
Powered by NewsLook.com
Beatings and Addiction: Pakistan Drug 'clinic' Tortures Patients

Beatings and Addiction: Pakistan Drug 'clinic' Tortures Patients

AFP (July 24, 2014) A so-called drugs rehab 'clinic' is closed down in Pakistan after police find scores of ‘patients’ chained up alleging serial abuse. Duration 03:05 Video provided by AFP
Powered by NewsLook.com
New Painkiller Designed To Discourage Abuse: Will It Work?

New Painkiller Designed To Discourage Abuse: Will It Work?

Newsy (July 24, 2014) The FDA approved Targiniq ER on Wednesday, a painkiller designed to keep users from abusing it. Like any new medication, however, it has doubters. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins