Wednesday, 4/16/97 Doctors pinpoint cause of dementia Discovery
may lead to treatment for AIDS-related illness
By Kathryn Combs Daily Bruin Contributor AIDS is currently known
as one of the most severe and debilitating diseases across the
world, and it is clear that no group is safe from infection. For
those infected, one of the most disabling symptoms is the onset of
AIDS-related dementia. UCLA researchers, in collaboration with the
University of Nebraska, the University of Arizona and the USC
Children’s Hospital, have recently made a discovery that could
revolutionize methods used to treat patients with AIDS-related
dementia. According to researchers, dementia is caused when the
AIDS virus traverses the blood-brain barrier, a protective coating
between brain tissue and the bloodstream, and seeps into the brain,
causing damage. The mechanism by which this occurs was largely a
mystery until this research. One of the primary researchers
involved in the project was Dr. Milan Fiala, an assistant professor
of medicine at UCLA. Fiala first devised the blood-brain barrier
theory in 1991. However, only until recent funding by the National
Institutes of Health (NIH) and a tightly knit collaborative
relationship between universities were researchers able to fully
examine this mechanism. Thoroughly researching the topic since
1991, Fiala said that the virus uses the body’s natural immune
reaction to "stow away" and cross the brain’s protective barrier.
"The brain is nourished by the blood to keep doing its work, and
the protection is such that nutrients can go into the brain … but
hopefully viruses cannot," Fiala said. "When immunological
reactions occur, the blood-brain barrier opens up and the immune
cells go in to do work in the brain. … They are going in there to
snatch any viruses that are already present, but in the process,
they may bring in another virus of their own," he added. According
to researchers such as Dr. Michael Graves, the presence of the AIDS
virus in the brain is not always immediately noticeable. Graves,
also an associate professor of neurology, further commented that
regardless of this, symptoms of dementia may not occur even when
the brain is already infected. "There are some people that become
demented at the first sign of disease, and in other people it is
late, and they’ve had the disease for many years," he said.
"There’s an initial entry of the virus (that occurs) very early
when people are still very healthy … but when they start to get
the dementia there may be more entry of virus," Graves said,
further explaining the findings of their study. According to
Graves, as the disease progresses, more of the virus is able to
enter the brain and break down the protective blood-brain barrier,
eventually causing significant debilitation. Dr. Howard Gendelman,
chief of the laboratory of viral pathogenesis and one of the
collaborators on this project, said that the AIDS virus does not
affect all patients in the same manner. In other words, it does not
always cause dementia. "The immune system is ravaged by the virus
(and) there is a breakdown of this blood-brain barrier in some
patients, (however) not in all patients," Gendelman said. "That
leads to the loss of mental function. How the blood brain barrier
becomes compromised (and) allows the virus to go across and ravage
the brain … is very critical in preventing the mechanism of this
most horrific complication of HIV," added Gendelman, explaining
that this protective barrier eventually becomes ineffective. "We
found that through the immunological activation of the immune
system … (allows) the blood cells to secrete neurotoxins that
break down the blood-brain barrier and … the ravaging effects of
these immune cells to penetrate from the blood into the brain,"
Gendelman added. Research by the University of Nebraska showed that
the active immune cells showed a 2,000 percent increase in the
ability to slip through the protective shield because of the
secretion of neurotoxins. As a result, these infected immune cells
then migrate into the brain, usually causing the severity of
dementia to worsen. Researchers are currently looking into the use
of anti-inflammatory drugs that may inhibit migration of infected
immune cells into the brain, revolutionizing current treatment for
AIDS patients. JUSTIN WARREN/Daily Bruin (Far right) Dr. Milan
Fiala, M.D., head researcher at UCLA on the cause of dementia for
AIDS patients, with colleagues (from right), immunologist Xaiohu
Gan, Dr. Michael Graves, head of the Neurovirology Laboratory, and
the Associate head of Neuorology, and post-doctoral fellow, Ling
Zhang. Markers For AIDS Dementia Complex Described Caring For
Someone With AIDS