In humans, decreased blood flow and oxygen to the infant brain is linked to premature birth and other irregularities during pregnancy, birth and early development. The phenomenon, which is called hypoxia ischemia, causes brain injury in approximately 2 of every 1,000 full-term human births and in a very high percentage of babies born before 34 weeks of gestation. Hypoxic ischemic brain injury can lead to seizures, a degenerative condition known as hypoxic ischemic encephalopathy, and mobility impairments including cerebral palsy.
When scientists temporarily lowered brain oxygen levels and brain blood flow in newborn mice whose mothers drank water mixed with pomegranate concentrate, their brain tissue loss was reduced by 60 percent in comparison to mice whose mothers drank sugar water or other fluids.
"Hypoxic ischemic brain injury in newborns is very difficult to treat, and right now there's very little we can do to stop or reverse its consequences," explains senior author David Holtzman, M.D., the Andrew B. and Gretchen P. Jones Professor and head of the Department of Neurology. "Most of our efforts focus on stopping it when it happens, but if we could treat everyone who's at risk preventively, we may be able to reduce the impacts of these kinds of injuries."
The study, which appears in the June issue of Pediatric Research, was conducted in collaboration with POM Wonderful, a U.S. producer of pomegranates and pomegranate juice, and scientists at the University of California, Los Angeles. Lead author David Loren, M.D., formerly a neonatal critical care fellow in the Department of Pediatrics, performed the research. He is now at the University of Washington in Seattle.
Holtzman's lab has been studying neonatal brain injury for more than a decade by temporarily reducing oxygen levels and blood flow in the brains of 7-day-old mouse and rat pups. The model produces brain injuries similar to those seen in human infants injured by hypoxia ischemia.
Pomegranates contain very high concentrations of polyphenols, substances also found in grapes, red wine, and berries that scientists have linked to potential neuroprotective and anti-aging effects.
Scientists gave pregnant female mice water with pomegranate juice, plain water, sugar water or vitamin C water to drink during the last third of pregnancy and while they suckled their pups for seven days after birth.
After performing the procedures that exposed mouse pups to low oxygen levels, scientists examined the brains, comparing damage to the cortex, hippocampus and the striatum. Researchers who conducted the examinations were unaware of what the pup's mother drank. Mice whose mothers drank pomegranate juice had brain injuries less than half the size of those found in other mice.
Much of the damage from hypoxia ischemia results when oxygen-starved brain cells self-destruct via a process known as apoptosis. Scientists found an enzyme linked to apoptosis, caspase-3, was 84 percent less active in mice whose mothers drank pomegranate juice.
Holtzman says the results suggest the need for studies of pomegranate juice's effects in humans, but he cautions that because of the relative unpredictability of hypoxia ischemia in newborns, it would be difficult to assemble a sufficiently large study group.
Hypoxic ischemic brain damage is frequently associated with premature delivery. The lungs, brain and circulatory systems in some premature babies are insufficiently mature to supply the brain with enough nutrients and oxygen outside the womb. Scientists know some of the factors that increase risk of premature birth, including diabetes, low economic status, youthful mothers, weakness in the cervix and a personal or familial history of miscarriage.
"One might advise this group that studies in animals have suggested drinking pomegranate juice may reduce the risk of injury from hypoxia ischemia," he says.
Holtzman's findings and other research into the potentially beneficial effects of pomegranate juice, red wine, and other natural foods form a neurological parallel to chemoprevention, an area of oncology research focused on finding naturally-occurring substances in foods that reduce the chances of developing cancer.
"For pregnant women previously interested in the neuroprotective effects of red wine, these results suggest that pomegranate juice may provide an alternative during pregnancy, when alcohol consumption is unacceptable because it increases risk of birth defects," Holtzman says.
Holtzman's group is attempting to isolate the neuroprotective ingredients in pomegranate juice as a possible prelude to concentrating those ingredients and testing their ability to reduce brain injury. They also plan to investigate the possibility that polyphenols from pomegranates and other natural foods can slow other neurological disorders including Alzheimer's disease.
Loren DJ, Seeram NP, Schulman RN, Holtzman DM. Maternal dietary supplementation with pomegranate juice is neuroprotective in an animal model of neonatal hypoxic-ischemic brain injury. Pediatric Research, June 2005, 858-864.
Funding from the Stewart and Lynda Resnick Revocable Trust and the National Institutes of Health supported this research.
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