AR-News: (US)"Our findings are in rodents and need to be confirmed in humans"

[Masako Miyaji]

http://www.sciencedaily.com/releases/2004/03/040322082903.htm

Source: American Neurological Association 
Date: 2004-03-22 

Researchers Identify Critical Link In Lead-Induced
Brain Swelling

Researchers have identified a key molecule through
which high doses of lead trigger brain edema, a
potentially fatal swelling. According to the report
published March 22 in the early on-line edition of the
Annals of Neurology, drugs that interfere with the
molecule can prevent edema in an animal model of lead
poisoning.

"Our findings are in rodents and need to be confirmed
in humans," cautioned senior author John Laterra, MD,
PhD, a professor, Departments of Neurology,
Neuroscience and Oncology, Johns Hopkins University
School of Medicine and the Kennedy Krieger Research
Institute

If confirmed, however, these results would justify
examining whether the same molecule plays a role in
the much more prevalent cognitive deficits caused by
smaller, more gradual exposures to lead in children. 

For many Americans, lead toxicity was thought to be a
thing of the past, abolished when the metal was
removed from paint in 1977. However, lead has recently
reappeared in news headlines about dangerously high
concentrations in some Washington, D.C., water
supplies.

For poor children living in houses with old, flaking
paint, lead poisoning has never ceased to be a health
issue. And indeed, recent scientific findings indicate
that even the tiniest amounts of lead can cause brain
damage in children. This has triggered calls for
stronger lead regulations.

Laterra, along with first author Mir A. Hossain, PhD,
and their colleagues have been studying the more
drastic type of lead poisoning caused by exposure to
very high levels over a short period. In adults, this
typically occurs in industrial settings and can lead
to peripheral nerve and kidney damage, among others.

Children are more vulnerable because their brains have
not yet developed adult safeguards against toxins.
Small children can get quite high brain exposures if
they ingest flakes of lead-based paint or inhale dust
containing old lead paint, in combination with lead
from other sources such as water pipes.

"Acute high-level lead toxicity, while less common now
in the U.S., continues in developing countries and
causes brain edema and even death," said Laterra.

Laterra and colleagues had previously found that a
protein called vascular endothelial growth factor
(VEGF) is elevated in nervous system cells exposed to
lead. VEGF is known to be able to trigger brain edema.

In the current experiments, the researchers found that
young rats that ingested high concentrations of lead
accumulated the metal in their brains. This was
accompanied by significant edema, as well as increases
in VEGF.

VEGF is part of a so-called biochemical "pathway."
Changes in the levels or activity of one molecule in a
pathway affects another, which affects another, and so
on down the pathway.

In an experiment that may point to improved treatment
for lead toxicity, Laterra and colleagues found that a
drug which blocks the ability of VEGF to effect
molecular changes inside cells prevented edema in the
young rats.

"It is possible that VEGF pathway inhibitors, if
approved by the FDA, could be used to prevent the
development of brain swelling in children acutely
intoxicated with lead. It is also possible that other,
more subtle, cognitive aspects of low-level lead
toxicity are caused by changes in VEGF levels," said
Laterra. 

Even if regulatory measures manage to eliminate most
sources of new lead in the environment, lead stays in
the environment for a long time. There remains a
pressing need to understand the mechanisms of lead
toxicity, conclude the authors in their article.

The Annals of Neurology, the preeminent neurological
journal worldwide, is published by the American
Neurological Association, the world's oldest and most
prestigious neurological association. The 1,400
members of the ANA--selected from among the most
respected academic neurologists and neuroscientists in
North America and other countries--are devoted to
furthering the understanding and treatment of nervous
system disorders. For more information, visit
http://www.aneuroa.org.

This story has been adapted from a news release issued
by American Neurological Association.




__________________________________
Do you Yahoo!?
Yahoo! Finance Tax Center - File online. File on time.
http://taxes.yahoo.com/filing.html