Stanford Report Online

Stanford Report, January 10, 2001
Brain cooling shows promise as technique to prevent long-term stroke damage


Cooling the brain may one day be a useful method for preventing stroke damage even when it's done as much as two hours after a brain attack, according to a study published by Stanford researchers in the January issue of the Journal of Neurosurgery.

The approach -- tested on rats but not on humans -- offers encouragement that patients could avoid the devastating and often permanent brain damage caused by the most common type of stroke if they are transported to a hospital where hypothermia, or subnormal body temperature, can be induced, said Gary K. Steinberg, MD, PhD, senior author of the study.

Experimental studies in the past three years have shown hypothermia to be effective in limiting brain damage after trauma, such as a blow to the head, even if treatment is delayed by several hours. Other studies found that hypothermia administered before or within minutes of a stroke was beneficial. But it wasn't known whether the stroke treatment would be effective if administered up to two hours later or whether it offered long-lasting protection.

"From a practical standpoint it's important to know how long we have before we must begin treatment. Because hypothermia has to be administered in a specialized clinical setting, treatment delays of several hours are almost inevitable," Steinberg noted.

In the Stanford study, scientists induced strokes in rats and treated a portion of them with hypothermia. Treatment was delayed for up to 180 minutes. After two months, 94 percent of the rats treated with hypothermia for two hours were alive, compared with 61 percent of the rats not treated with hypothermia. The treatment "conferred significant degrees of neuroprotection in terms of survival, behavioral deficits and histopathological [tissue] changes, even when its induction was delayed by 120 minutes" after induced stroke, the researchers said.

Rats who received the treatment also were more alert with fewer apparent effects of brain damage one week later, indicating hypothermia may have broad implications for treating stroke patients.

Scientists don't fully understand why lowering the brain's temperature prevents damage, but Steinberg and colleagues at Stanford recently received a five-year, $2-million grant from the National Institutes of Health to explore its therapeutic effects.

Brain cells die when they are deprived of oxygen and can no longer control designated body functions. Stroke damage is often permanent because damaged brain cells are not normally replaced.

Scientists believe cold temperatures may preserve and protect cells when the brain's oxygen supply is cut off. Why this occurs isn't precisely understood, Steinberg said, but hypothermia is known to decrease the release of detrimental neurotransmitters and other toxic substances.

Also, hypothermia reduces inflammation or lowers the brain's need for nutrients, including oxygen and glucose. In a complex way, scientists speculate, cold temperatures may prevent oxygen components from damaging cells that control brain function. "Hypothermia may work because of a combination of some or all of these potentially beneficial effects," Steinberg said.

To induce hypothermia, doctors wrap patients in specially designed cooling blankets. Ice water is pumped through a network of hoses in the blanket, lowering the body and brain temperatures to about 88 degrees F.

The journal article noted that "whole-body hypothermia may not be the most desirable way to achieve the targeted temperature in humans," and methods for targeted cooling of the brain itself are being developed.

Other researchers in the study are Carolina M. Maier, PhD, postdoctoral fellow in neurosurgery; Guo Hua Sun, MD, PhD, research assistant; David Kunis, BS, research assistant; and Midori A Yenari, MD, assistant professor (research) of neurosurgery.

Yenari and Steinberg are also researchers on the grant to study hypothermia's protective effect, along withPak H. Chan, PhD, professor of neurosurgery, and of neurology and neurological sciences; and Raymond Sobel, associate professor of pathology. Also on the project is Joseph Beckman, professor of anesthesiology, biochemistry and molecular genetics, and of neurobiology at the University of Alabama-Birmingham.