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Glucose triggers brain cell death in rats after hypoglycemic coma

Brain damage that was thought to be caused by hypoglycemic coma actually occurs when glucose is administered to treat the coma, according to a study in rodents led by researchers at the San Francisco VA Medical Center.

The results are surprising, say the authors, and may be of clinical significance for the treatment of diabetics in hypoglycemic coma, though they caution that the results cannot be immediately extrapolated to humans.

Insulin is an essential hormone that moves glucose from the bloodstream to individual cells, where it is broken down and used for energy. Diabetics do not produce enough of their own insulin and must take it several times a day.

A severe insulin overdose can reduce levels of glucose in the blood to extremely low levels a condition known as hypoglycemia and cause hypoglycemic coma, resulting in destruction of neurons in the hippocampus and cerebral cortex, which are essential to memory and cognition.

"This study tells us for the first time that, in rats, the brain damage occurs not during the coma, but after it, when we give them glucose and their blood glucose levels return to normal," says principal investigator Raymond A. Swanson, MD, chief of the neurology and rehabilitation service at SFVAMC.

Furthermore, says Swanson, he and his fellow researchers have identified the cause of the damage: the sudden return of glucose to the brain activates the enzyme NADPH oxidase, which in turn initiates a process of oxidative stress that is fatal to neurons.

Oxidative stress occurs when cells are poisoned by highly reactive forms of oxygen. Previously, it had been assumed that oxidative stress in neurons was initiated primarily by mitochondria, which process oxygen for energy within cells.

The paper appears in the April 2007 issue of the Journal of Clinical Investigation.

In their study, the researchers subjected rodents to a model of severe hypoglycemic coma. "
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Contact: Steve Tokar
steve.tokar@ncire.org
415-221-4810 x5202
University of California - San Francisco
4-Apr-2007


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