Thursday, June 05, 2008

The Scientist : NewsBlog : Add brain cells, remove seizures [4th June 2008 05:11 PM GMT]

Add brain cells, remove seizures
Posted by Edyta Zielinska
[Entry posted at 4th June 2008 05:11 PM GMT]

For the first time, researchers have succeeded in reversing a condition that causes seizures in mice by transplanting progenitor cells into the brain. The finding, reported in this week's Cell Stem Cell, has important implications for treating a class of childhood diseases marked by myelin insufficiency.

"These are spectacular results," said Ian Duncan at the University of Wisconsin, Madison, who was not involved in the study. "I like to think we've done pretty good work," said Duncan, who had been working on similar studies, "but this looks like normal brain," with no obvious lack of myelination, he said.

Myelin, produced by glial cells, insulates nerve axons and aids the conduction of the nerve impulses. Children with congenital childhood diseases of myelin insufficiency, such as Pelizaeus-Merzbacher disease and some forms of cerebral palsy, can experience life-threatening seizures and other neurological disorders.

For years, Steven Goldman's group at the University of Rochester Medical Center has been transplanting human glial progenitor cells into newborn shiverer mice -- a mutant strain incapable producing myelin sheaths -- to try to restore the myelin. Although previous studies have shown that the injections could help myelinate brain cells, "neither in my prior studies or others' has there been any functional benefit," said Goldman.

Goldman designed a new transplant protocol by studying how injected cells had spread and engrafted in past studies. He calculated that he would have to transplant almost three times as many cells into five locations in the brain to get sufficient coverage, penetration and engraftment. Without myelin, mice typically show signs weakness in the hind limbs, develop frequent seizures, and usually die between 18 and 20 weeks of age.
When they were treated with the new transplant protocol, six out of the 26 mice developed myelin in their brain and in "every nook and cranny of the central nervous system," and suffered fewer seizures. These mice also survived for a full year, at which point they were sacrificed. (To see movies of mice before and after treatment click here. )

Because the transplanted cells were human glial progenitor cells, the six mice that survived essentially developed a humanized central nervous system. This chimeric mouse model could help researchers study human neuronal cells in vivo in a way they have never been studied before, said Goldman -- "from the standpoint of looking at physiology and gene expression patterns in response to injury," as well as screening pharmacological agents.

Although the remaining 20 mice treated with glial progenitors also grew myelin, that growth happened more slowly, and the animals died from seizures. "We believe that there are critical centers in the brain stem that need to be myelinated quickly," said Goldman. If those treated mice had more time to grow myelin before the seizures started, they might have gained the critical level of coverage necessary to protect them, he believes. He plans to repeat the study with anti-epileptic drugs to see if he can get mice through that critical period. "This is a complex story that we're still working through," said Goldman.


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