BOSTON - Scientists say they have succeeded in activating an
overlooked self-repair system that enables animal brains, and
potentially those of humans, to make new nerve cells and heal
themselves from the inside.
The remarkable finding topples long-held beliefs that the brain
has no way to fix itself, and could open a new route to treating
everything from Alzheimer's disease to strokes.
For now, researchers cannot try the strategy in humans: They had
to kill brain cells in the experimental mice to switch on their
brains' nerve-generating capacity.
But the researchers are hunting for other methods, such as
drugs, that could turn on the hidden maintenance kit in the brain.
The discovery is ``enticing,'' said researchers commenting on the
work.
``There is a long way to go,'' wrote Drs. Anders Bjorklund and
Olle Lindvall of Lund University in Sweden, but learning how to
switch on the repair system ``might eventually lead to a powerful
tool for brain repair in human disorders of the central nervous
system,'' they said.
The prominent Swedish brain researchers made the comments in an
article accompanying the report in the current issue of Nature. The
report is by Dr. Jeffrey Macklis, an associate professor of
neurology and neuroscience at Harvard Medical School and Children's
Hospital, and his colleagues, Sanjay Magavi and Blair Leavitt.
Magavi, a graduate student, should be credited as the ``motive
force'' in the study, Macklis said.
The findings are the latest in a string of intriguing
discoveries in the past few years about ``neural stem cells,''
previously unrecognized immature cells that can generate all the
major types of cells in the brain. Already, scientists have cured
mice of some severe brain disorders by implanting neural stem cells
into their brains.
It had been long thought that the brain was incapable of
changing or repairing its nerve circuits once it had fully
developed. In fact, people were thought only to lose nerve cells as
they aged. Scientists believed that was a product of evolution in
which the brain was prevented from making new nerve cells, or
neurons, after childhood because cell growth would increase the
chances of making harmful neural connections.
``We now know that this view isn't correct,'' said Macklis.
Macklis said in an interview that in two areas of the more
primitive part of mammals' brains, neural stem cells are known to
generate new neurons, though not in great numbers, in response to
damage. But it seemed the cells could not make neurons in the
higher-function parts of the brain, like the cerebral cortex.
Researchers attempted to see whether the neural stem cells, also
called neural precursors, could move to the cerebral cortex and
generate neurons to fix damage there.
To test this idea, Macklis and his colleagues injected a
light-sensitive chemical into a certain area of brains of adult
mice. Two weeks later they opened the skulls and shined a light on
that tiny area, and the activated chemical caused hundreds of
thousands of neurons to commit suicide, a process called apoptosis.
The death of these neurons caused the neural stem cells to
become active, to migrate to the damaged brain area, to turn into
the correct type of neurons, and make long-distance connections to
the proper places, Macklis said. Their repair route took them only
a fraction of a millimeter, ``but that's a long way for a nerve
cell'' in a mouse brain, he added.
The goal now, said Macklis, is to discover what signals are
received by the neural stem cells to summon them. That might enable
scientists to design drugs that would recruit the neural stem cells
and, it is hoped, make it possible ``to do the repair from the
inside'' of the brain rather than needing cell implants.
Dr. Paul Sanberg, chair of neuroscience at the University of
South Florida, termed the work ``very important.'' But he added,
``the question will be how much neurogenesis will you see in
response to large injuries in clinical studies?'' Neurogenesis is
the creation of neurons.
Bjorklund and Lindvalle, in their commentary, said, ``These
cells might represent a dormant capacity for neuronal repair,'' but
pointed out that in the mouse experiment only a small fraction of
damaged neurons were replaced by the stem cells. ``It is
inconceivable'' that such a small number of nerve cells ``would
allow significant functional recovery.''
However, they agreed that finding the signals that recruit the
repair cells will be key, because those signals might turn out to
be restarting a repair process that occurs in the brain during
early development and which might lead to better treatments for
brain disorders.
