Neuro-Repair Research

Ian Goddard igoddard at
Tue Feb 19 20:56:08 EST 2002

Neural Stem Cells Move To Damaged Areas Of Brain After Injury; Adult
Mammalian Brain Has Potential To Heal Itself, Says Scientist 

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

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.

 "To lengthen thy life, lessen thy meals." Benjamin Franklin 

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