A study conducted by researchers at Columbia University Vagelos College of Physicians and Surgeons discovered that an injectable emulsion containing two omega-3 fatty acids contained in fish oil significantly reduced brain damage in newborn rodents after a disturbance in the flow of oxygen to the brain near delivery.
Brain damage as a result
of inadequate oxygen is a serious complication of labour and delivery that
affects one to three out of every 1,000 live newborns in the US. Among babies
who survive, the illness can cause cerebral palsy, cognitive disability,
epilepsy, pulmonary hypertension, and neuro developmental disorders.
"Hypoxic brain
injury can have devastating, lifelong consequences, and we suggest our novel
therapeutic approach using intravenous omega-3 emulsions could markedly reduce
these adverse outcomes," said Richard Deckelbaum, a professor of nutrition
and pediatrics and a coordinating author of the study.
The study also found
that the novel omega-3 preparation is far more effective in rodents when
compared to therapeutic hypothermia, the current standard therapy for this
condition and the only one approved by the FDA. This treatment, which involves
using cooling blankets for three days, only benefits about 15% of patients and
can cause heart and respiratory complications.
"We need to find
another treatment for hypoxic brain injury that will be much more effective and
feasible than therapeutic cooling and can be used in the immediate hours after
the injury when therapy is likely to be most effective," said Hylde
Zirpoli, an associate research scientist in Deckelbaum's group and senior
author of the study.
Previous studies by
Deckelbaum's team and others have shown that omega-3 emulsions--tiny droplets
of omega-3 fatty acids dispersed in liquid--may have neuroprotective effects
and that omega-3 fatty acids found in fish oil reduce inflammation and cell
death caused by oxygen deprivation. But the bioactive compounds contained in
commercially available oral omega-3 supplements take weeks or months to have an
effect, so they aren't ideal for protecting organs immediately after injury.
The Columbia team
developed an injectable omega-3 therapy that can be used in just such
situations. The therapy is a diglyceride formulation--two omega-3 fatty acids,
DHA and EPA, bound to a glyceride molecule--which enhances their ability to
emulsify into tiny, concentrated particles. These fatty acids are also found in
fish oil, though fish oil and dietary sources of fatty acids are mainly
triglycerides, which have three fatty acids per molecule.
The new diglyceride is
predicted to cause a higher concentration of omega-3 molecules to rapidly
penetrate the blood-brain barrier.
The researchers gave the
therapy to week-old mice and rats with hypoxic brain injury. The experimental
emulsion reduced brain damage far more than a commercially available omega-3
injectable emulsion (only approved as a nutritional supplement for infants with
intravenous nutrition-related liver disease). Doses for both omega-3
preparations were similar.
The experimental
emulsion may have worked better than the commercial emulsion because it was
absorbed into the animals' bloodstream two times faster.
The researchers also
found that animals treated with the new therapy had normal motor coordination
and reflexes--indicators of neurologic function--similar to the animals with no
brain injury.
"The omega-3
diglyceride emulsion not only prevented brain cell death, but it also preserved
neurologic function, which is important in reducing the cost of disabilities,
both to the patient's well-being and to the health care system,"
Deckelbaum says.
The researchers hope to
begin clinical trials in newborns within two years and plan to expand studies
on the therapy's effectiveness in preventing damage to the central nervous
system in animals with traumatic brain injury and spinal cord injury.
Additional studies will explore applications in other acute injuries and conditions
in which oxygen deprivation causes organ damage, including heart attack and
stroke.
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