X-Message-Number: 13991
Date: Thu, 22 Jun 2000 15:59:24 -0400
From: Jan Coetzee <>
Subject: Healing a human brain

 Healing a human brain from the inside out was supposed to be
impossible. The evolutionary choice for mammals was believed to be
between
a
brain that was fixable and a brain that was too complex to tinker with
after
it was formed, especially from the inside. Now comes the discovery from
a
Children's Hospital research group, published today in the journal
Nature,
that our brain's nerve cells or neurons could one day be induced into
healing themselves.
      The paper from Jeffrey Macklis, Harvard Medical School associate
professor of neurology at Children's Hospital, and his associates Sanjay

Magavi and Blair Leavitt, flies in the face of a century of neuroscience

conviction that in mammals the brain and particularly the cerebral
cortex
is
incapable of healing itself a dogma that a series of recent experiments
has
shaken.
      "Somewhere during evolution it was believed," Macklis says, "our
brain, unlike the brains of other lower vertebrates, decided it would no

longer do self-repair. The assumption has been that because we as
mammals
build a very complex brain, we don't want to mess around with it. We
know
now that this view isn't correct."
      The Macklis group was able to induce stem cells deep in the
cerebral
cortex of adult mice to replace damaged neurons. These new neurons grew
from
already present immature precursor cells into fully formed, connected,
and
mature replacements. These home grown neurons demonstrate for the first
time
that the brain can heal itself from the inside out, without
transplantation.
      This breakthrough in fundamental neural cell biology is a long way

from clinical application but Macklis says that if the mechanisms at
work
here can be understood and controlled, it may open a new avenue someday
for
treatment of degenerative brain diseases and central nervous system
injuries.
      Until recently, neuroscience held that neural precursor cells,
active
during fetal development, shouldn't exist in adults and yet recent
research
uncovered them in the forebrains of mice. Other work has shown that
precursors can form new neurons in two limited areas of the brain. The
dogma
said that diseased or damaged neurons in the cerebral cortex can't be
replaced and yet Macklis's lab has had success with injecting lab-grown
neural precursors into the cortex of mice and watching them replace
dying
cells. Still even while working with transplantation, the investigators
proceeded along another route, pursuing what Macklis calls "the
futuristic
idea that one might be able to activate neuronal repopulation and repair

from the inside out."
      The trick was to reopen the genetically controlled pathway that
once
allowed nerve cells to change. Macklis and his colleagues reasoned that,

even suppressed, the instructions for the pathway must still be encoded
in
DNA. But how to signal them?
      Macklis's team found the signals by using biophysical targeting to

convince certain neurons to undergo apoptosis, or cellular suicide. Then

they introduced chemical labels revealing whether or not existing
precursor
cells in the cortex were multiplying and taking their places as new
neurons.
      The investigators found that the endogenous neural precursors
already
were multiplying, as evidenced by the appearance of labeled BrdU, a
marker
of DNA replication. Then they spotted Doublecortin, a protein expressed
only
by migrating neurons, Hu, an early neuronal marker, and NeuN, a marker
expressed only by mature neurons, indicating the precursors were
progressively developing into mature neurons. Confirmation that the
replacements were projecting their axons to make connections with other
neurons came from additional anatomical labeling with dyes.
      Macklis warns that this experiment is merely a first crude step in

exploring the pathway of neural regeneration. "Not for a moment would
any
of
us suggest that to repair the brain we want to go around inducing cell
death. Rather, it's that we want to use this as an experimental tool to
dissect out what the controls are. Our approach of targeted apoptosis,
or
cell death, has given us a crude external lever over a whole program of
genes that we're investigating now. What we've done in this study is to
turn
on the whole program, all at once. What we'd really like to do is to
define
what the sequence and combination of the individual molecules is."
      "Now comes the hard work," says Macklis.

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Early Measles Infection Linked To Inflammatory Bowel Disease

     [Andrew Wakefield s research into the connection between vaccines
and
autism discovered connections between autistic children with
inflammatory
bowel disease and the presence of vaccine measles virus in the gut. ]
http://ipn.intelihealth.com/IPN/ihtIPN?st=23883&t=7223&c=286871

      Reuters Health - Early measles infection may increase the risk of
developing Crohn's disease and ulcerative colitis, according to
researchers
from the Mayo Clinic.
      The report is the latest in a series of reports over the last few
years, previously reported by Reuters Health, which have either
bolstered
or
questioned the link between measles infection and inflammatory bowel
disease.
      Dr. Darrell S. Pardi and colleagues from the Rochester,
Minnesota-based institution, describe their study in the June issue of
The
American Journal of Gastroenterology. They suggest that the idea that
the
measles virus can cause inflammatory bowel disease is "biologically
plausible", given that the virus can infect and persist in endothelial
cells
in the gastrointestinal tract and cause an immune response with giant
cell
formation.
      In the study, they identified individuals who had been diagnosed
with
measles before the age of 5 years from 1950 to 1966 through the Mayo
Clinic
and the Rochester Epidemiology Project. Of this initial group of 1,164
eligible cases, 662 completed a questionnaire to determine if the
patient
had subsequently developed Crohn's disease or ulcerative colitis, or
symptoms of undiagnosed disease.
      Overall, the researchers found six cases of Crohn's disease and
six
cases of ulcerative colitis that could be confirmed by the patients'
physicians. Based on the incidence of cases in Olmsted County,
Minnesota,
they would have expected significantly fewer cases: 1.9 for Crohn's
disease
and 2.0 for ulcerative colitis.
      Seventy-five percent of the cases had measles before the age of 2
years, the authors note, but this did not reach statistical
significance.
      Noting that others have found no difference in the rate of measles

infection in those diagnosed with inflammatory bowel disease, Dr. Pardi
and
colleagues suggest that "infection before the development of full
immunological competence may lead to viral persistence." They also
suggest
that other factors, such as infection with mumps virus, may contribute
to
the development of inflammatory bowel disease.
      The investigators also emphasized that their study did not
consider
the effect of measles vaccination, and "unless more compelling data
become
available to implicate measles vaccine as a risk factor for inflammatory

bowel disease, we fully support the current recommendation for universal

vaccination against measles."
      Am J Gastroenterol 2000;95:1480-1485.
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