High-Altitude Cerebral Edema Likely Caused By Leaks In Blood-Brain Barrier

April 28, 1998

PHILADELPHIA, Penn. -- The latest high-tech gear can't protect climbers on Mount Everest from one of the hazards feared most by those who spend time at extreme heights -- oxygen deprivation, or hypoxia, resulting in the potentially lethal brain swelling known as high-altitude cerebral edema.

Research conducted at the University at Buffalo suggests that high-altitude cerebral edema is caused by a disruption in the blood-brain barrier, the specialized layer of cells in cerebral blood vessels that, under normal conditions, allow only certain substances to pass into the brain's circulation.

John A. Krasney, Ph.D., UB professor of physiology and a specialist in hypoxia, will present the findings here today (April 28, 1998) at the 66th annual meeting of the American Association of Neurological Surgeons in Philadelphia.

Krasney and colleagues in UB's Hermann Rahn Laboratory of Environmental Physiology have developed an animal model using sheep for studying hypoxia and cerebral edema in an effort to learn more about how and why these conditions develop and their effect on cognitive function.

"Brain swelling, and also pulmonary edema [fluid in the lungs], is one of the major problems at high altitude and we don't really know the cause of either," Krasney said. "It is not lack of oxygen per se. At high altitude, the brain has an adequate supply of oxygen, because blood flow increases to compensate for the lower concentration of oxygen in the air. Yet people still get sick."

In its mildest form, swelling of the brain brings on the headaches and nausea characteristic of acute mountain sickness. In its most severe form, unrelieved by retreat to lower elevations, brain swelling advances to high-altitude cerebral edema, which causes disorientation, impaired mental function and death.

Information gained from the study of high-altitude cerebral edema and hypoxia is relevant to many people other than those wealthy enough to afford an Everest trek, Krasney noted.

"Thirteen million people go to Colorado every year to ski and 65 percent develop at least a headache," he said. "Twenty-five percent develop acute mountain sickness, and 1-2 percent develop high-altitude cerebral edema." Hypoxia also is associated with obstructive lung diseases, sleep apnea and other disorders.

Krasney's research using sheep has shown that the symptoms of high-altitude cerebral edema are not caused by an inadequate supply of oxygen or glucose to the brain. Rather, it appears that an accumulation of malfunctions create enough cerebral blood pressure to force apart cells of the blood-brain barrier and allow fluids to accumulate in and around brain tissues.

They theorize that acute hypoxia may allow a decline in cyclic adenosine monophosphate (cAMP), a chemical messenger involved in regulating capillary permeability. The decrease in cAMP may allow the cerebral capillaries to leak.

In addition, Krasney said, it is possible that, in the presence of hypoxia, another chemical messenger, cyclic guanosine monophosphate (cGMP), acts with nitric oxide, a vasodilator, to promote and sustain permeability of the blood-brain barrier. The combined influence of actions could allow fluid to accumulate in the intracellular spaces, he said.

Yet another mechanism that may be at work involves elevated levels of leukocytes that may cling to the lining of cerebral blood vessels and cause leaks in the blood-brain barrier.

Krasney and colleagues are attempting to clarify further the importance of these mechanisms in the development of acute mountain sickness and high-altitude cerebral edema.

Their research is supported by the National Heart, Lung and Blood Institute.
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University at Buffalo

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