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BOSTON,
Mass. - Primitive neural cells in the brains of laboratory rats
respond to acute brain injuries by moving to the injured area and
attempting to form new neurons, according to University
of Michigan neurologist Jack M. Parent, M.D. Understanding how
this self-repair mechanism works could someday help physicians reduce
brain damage caused by strokes or neurodegenerative diseases.
In a presentation
here today at the American Association for the Advancement of Science
meeting, Jack M. Parent, M.D., an assistant professor of neurology
in the U-M Medical
School, described results from a series of his experiments with
laboratory rats. Prolonged epileptic seizures or strokes in these
rats caused neural precursor cells called neuroblasts - cells midway
in development between a stem cell and a fully developed neuron
- to multiply and form neural chains that migrated across the brain
to the site of injury.
"What's
fascinating is that neuroblasts responded similarly to both types
of brain injury," says Parent. "There's some cue in common
that activates their development and growth. We don't know what
it is, but we are looking for candidate molecules - growth factors
or neurotrophic factors - that stimulate the proliferation and migration
of precursor cells."
Parent cautions
that, while his results are intriguing, many years of research at
the molecular level and in animals will be necessary before human
clinical trials could even be considered. "It's not enough
to stimulate the development of neuroblasts in human brains and
hope they do what you want them to do," Parent says. "There
can be harmful consequences."
Until recently,
scientists believed the mammalian adult central nervous system -
the brain and spinal cord - was incapable of generating new neurons
from adult stem cells, a process known as neurogenesis. But now
scientists know that precursor cells in a part of the brain called
the subventricular zone or SVZ continue to produce new neurons throughout
life for a part of the brain called the olfactory bulb, which processes
scent. Another area of the brain called the dentate gyrus also generates
neuroblasts, which form neurons in the hippocampus -- the section
of the brain involved in learning, memory and regulating emotions.
"Many other sites in the brain's cortex contain neural progenitor
cells, also, but they never develop into neurons," Parent adds.
Prolonged epileptic
seizures cause widespread, diffuse damage to neurons in the brain's
hippocampus and other parts of the limbic system -- according to
Parent, who specializes in epilepsy research. When he examined slices
of brain tissue from rats with seizure-induced damage using a special
labeling technique that marks rapidly dividing cells, Parent found
a significant increase in neuroblast development in the dentate
gyrus and the sub-ventricular zone.
"Neuroblasts
linked together to form long chains that migrated to the olfactory
bulb through tubes formed by astrocytes, or neural structural support
cells," Parent says. "We also found neuroblasts outside
the olfactory bulb streaming in chains toward the forebrain, but
most died before they developed into neurons."
Two weeks after
he induced cerebral infarcts or strokes in rats, Parent found a
major increase in the number of neuroblasts migrating toward the
injury site. Five weeks after the stroke some had developed into
neurons. "Most importantly, some of the newborn neurons that
migrated to the injured striatum, a motor control area of the brain
affected by the stroke, appeared to develop into neurons specific
to the striatum," Parent adds.
"Our results
show that injury definitely induces proliferation of neuroblasts
in the brain. They start to migrate to the injured area and develop
into neurons. Some even become neurons appropriate for the injured
area," Parent says. "Because the precursor cells move
through tubes formed by proliferating astrocytes, it is possible
that astrocytes control neurogenesis. More research will be needed
to know for sure."
Migration of
neuroblasts after injury to the mature brain may not always be beneficial,
however. Parent and others have shown that after prolonged seizures,
neuroblasts in the dentate gyrus migrate to an area called the dentate
hilus where they don't belong. Even though they are in the wrong
place, these neuroblasts still appear to develop into dentate granule
cells.
"However,
they appear to be abnormally hyperexcitable and wire into existing
nerve cell networks in a way that may lead to seizures," Parent
says. "This suggests that making more new neurons after injury
is not always a good thing for brain function."
Despite such
obstacles, the idea that the brain can replace nerve cells lost
to injury opens up new avenues for potential therapies. Even though
the brain's attempt to repair itself is imperfect, Parent believes
increased understanding of the process could prove to be important
for individuals with brain damage. "You don't have to perfectly
rebuild the brain to improve significantly the patient's quality
of life after a stroke," he says. "If we could learn how
to repair even half the damage, it may be enough."
Parent's research
on injury-induced neurogenesis is supported by the National Institute
for Neurological Disorders and Stroke (NINDS) of the National Institutes
of Health and the Parents Against Childhood Epilepsy (PACE) Foundation.
Written
by Sally Pobojewski
For more
information, contact Sally Pobojewski, AAAS Press Room or
734-615-6912 or 734-764-2220, or by e-mail.
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