For release: Tuesday, January 13, 2004
Scientists studying an animal model of stroke have learned that the brain reacts to the trauma caused by a mild stroke in a way that serves to protect it from a subsequent injurious attack. The discovery may aid in the development of medications for persons at risk of stroke.
Stroke is the nation's third largest killer. There are as many as 700,000 strokes in the U.S. per year and 150,000 deaths as a result. The majority of strokes are ischemic , caused when a clot suddenly blocks blood flow to a vein or artery. Disabilities that can result from stroke include paralysis, cognitive deficits, speech problems, emotional difficulties, daily living problems, and pain.
Researchers Mary Stenzel-Poore, Ph.D., Oregon Health & Science University School of Medicine, and Roger Simon, M.D., Legacy Health Systems, led colleagues in testing the hypothesis that "ischemic preconditioning" naturally provides protection against a later, prolonged ischemic stroke. This preconditioning is based on a model which states that an organism, if given time to adjust to a trauma, will become stronger and more able to resist later trauma that might otherwise be lethal. The study was funded by the National Institute of Neurological Disorders and Stroke (NINDS) and published in The Lancet .*
The researchers studied gene expression and cellular mechanisms in normal mice and in a mouse model of stroke that was preconditioned (these mice had their cerebral artery blocked for 15 minutes, resulting in small protective strokes called transient ischemic attacks or TIA). The preconditioned mice showed an innate reprogramming of certain gene expression that led to a 70 percent decrease in brain damage during a second larger stroke.
"These results show that the body is able to reprogram or change its genetic response in anticipation of a future, larger stroke," said Dr. Simon. "Several systems were found to adapt to TIA insult and either increase or decrease gene expression in a way that protects the body." The most striking changes in gene profiles were in response to ischemic injury following preconditioning. In response to an induced stroke, the genetic activity in preconditioned animals was found to slow metabolism, conserve cellular energy, and prevent blood clotting. Other changes seen in preconditioned mice included decreased blood flow and limited glucose and oxygen intake similar to that seen in hibernation.
"The genetic changes that occur in animals preconditioned for stroke are very similar to those that occur in hibernating animals, providing an evolutionary basis for this neuroprotective response," noted Dr. Stenzel-Poore. "Our findings link preconditioning in the brain with systemic effects of longer blood clotting times, which would be an important neuroprotective strategy against ischemic stroke."
Ischemic tolerance studies led by John Hallenbeck, M.D., NINDS intramural stroke branch chief, are revealing a cellular mechanism in hibernating ground squirrels that may protect the nervous system from being damaged during the profound reduction in organ blood flow, greatly reduced capacity to delivery oxygen, and extremely cold temperatures (hypothermic stress) that characterize hibernation. "A better understanding of the body's naturally-occurring neuroprotective mechanisms may lead to new therapies and/or preventive measures for persons at high risk of ischemia and other neurological disorders," said Dr. Hallenbeck.
The findings may lead to preventive medicines that target certain genes and/or a combination therapy to address the many aspects of stroke.
For more information on stroke, please refer to the NINDS Stroke Information Page
*"Effect of ischaemic preconditioning on genomic response to cerebral ischaemia: similarity to neuroprotective strategies in hibernation and hypoxia-tolerant states." Stenzel-Poore, Mary P; Stevens, Susan L.; Xiong, Zhigang; Lessov, Nikola S.; Harrington, Christina A.; Mori, Motomi; Meller, Robert; Rosenzweig, Holly L.; Tobar, Eric; Shaw, Tatyana E.; Chu, Xiangping; Simon, Roger P. The Lancet, Vol. 362, September 27, 2003, pp. 1028-1037.
- By Paul Girolami
Last Modified December 8, 2015