(Philadelphia, PA) - Researchers at the University
of Pennsylvania School of Medicine discovered that children
with autism showed signs of abnormal blood-vessel function and damaging
levels of oxidative stress compared to healthy children. The children
with autism possessed levels of biochemicals that indicate the presence
of constricted blood vessels via the endothelium (the cells that
line vessels) with a higher tendency to form clots (through cells
By exploring the relationship between oxidative stress and blood-vessel
function in autistic patients, investigators hope to find new therapeutic
options for this syndrome. The researchers, led by Domenico
Pratico, MD, Associate Professor of Pharmacology, published
their findings in the August issue of the Archives of Neurology.
According to the Autism Society of America, the reported number
of autism cases is increasing 10 to 17 percent per year in the United
States. Autism, an early onset neurological disorder, is characterized
by impaired social interactions, limited verbal and nonverbal communication,
and repetitive and restricted behavioral patterns. Patients with
autism can differ in the severity and scope of their symptoms, suggesting
that multiple factors contribute to explaining the disorder’s
symptoms. Previous studies at other institutions have shown that
autistic patients have reduced cerebral blood flow, presumably due
to constricted blood vessels in the brain, versus healthy controls.
Urinary samples of autistic children who were similar in age and
healthy controls were provided by the Pfeiffer Treatment Center,
where patients were diagnosed with autism disorder and evaluated.
Patients were excluded from analysis if they had ever received anti-oxidant
treatments or medicine with any known anti-oxidant effect; if they
suffered from chronic illnesses, such as depression, psychosis,
or inflammatory disorders; and/or if they were sick at the time
of the sample collection. These strict criteria resulted in the
small sample size in this preliminary study: 26 children with autism
and 12 healthy controls.
Pratico’s team measured isoprostane, a biomarker for oxidative
stress; thromboxane, an index of platelet activation; and prostacyclin,
a measure of blood vessel activation in the samples. “This
study represents the first observation that the rates of thromboxane
and prostacyclin synthesis are both not only significantly increased
in autism, but are closely correlated with the rate of oxidative
stress,” says Pratico. Compared with controls, children with
autism had significantly higher urinary levels of isoprostane, thromboxone,
Oxidative stress is the result of an excessive formation of chemically
unstable byproducts, called free radicals, within the cell. Under
normal conditions, the cell is able to destroy the free radicals.
However, when excessive free radicals accumulate, these molecules
mount an attack against the cell in search of chemical stability.
“During oxidative stress, it is as if the free radicals have
only one leg,” explains Pratico. “They are searching
for the second leg in order to keep from falling. Unfortunately,
the ability of the excessive free radicals to reestablish their
chemical equilibrium comes always with a price for the organ --
irreversible cellular and organ damage.” Free radicals can
damage cell membranes, proteins, and genes by oxidation -- the same
chemical reaction that causes iron to rust.
Pratico and colleagues measured levels of isoprostane, the chemical
byproduct of free radicals attacking fat cells and found that patients
with autism possess nearly double the level of oxidative stress
than that measured in healthy controls.
The samples from autistic patients also revealed a biochemical imbalance
in the patients’ blood vessels, resulting in high levels of
thromboxane - an indicator of platelet activity - and prostacyclin,
an indicator of constricting endothelial cells. During normal function,
thromboxane and prostacyclin work together to maintain the integrity
of vessels. In response to different kinds of stress, platelets
release thromboxane, which causes vessels to contract. The endothelium
responds to elevated levels of thromboxane by releasing prostacyclin.
This event counterbalances the effect on vessels, inducing dilation
of the vessel and, in turn, more blood flow.
Autism is a complex neurological disorder and oxidative imbalance
is one feature of the autistic syndrome. Several lines of evidence
support the hypothesis that oxidative imbalance may also play a
role in this disease: autism is characterized by an impaired anti-oxidant
defense system, higher free-radical production, and improvement
of behavioral symptoms after taking anti-oxidants.
“In general, it is known that abnormalities in blood vessels
can be clinically reflected by an abnormal blood flow,” says
Pratico. “In this regard, it is interesting that earlier neuroimaging
studies of autistic children have demonstrated a reduced amount
of blood reaching the brain. Shedding more light on the relationship
of oxidative stress and blood-vessel health to the pathology of
autism could lead to improvements in therapy.”
Study co-authors are Yuemang Yao from Penn; William J. Walsh, Pfeiffer
Treatment Center (Warrenville, IL); and Woody R. McGinnis, Oxidative
Stress in Autism Initiative (Ashland,OR). The research was supported
in part by the Pfeiffer Treatment Center.
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