You are here
Research Offers New Target for Stroke Treatments
Looking for ways to improve outcomes for stroke patients, the researchers used candesartan &emdash; a commonly prescribed drug for lowering blood pressure &emdash; to identify specific growth factors in the brain responsible for recovery after a stroke.
The results were published online in the Journal of Pharmacology and Experimental Therapeutics.
Although candesartan has been shown to protect the brain after a stroke, its use is generally avoided in this setting because lowering a person's blood pressure quickly can cause problems, such as decreasing much-needed oxygen to the brain.
“The really unique thing we found is that candesartan can increase the secretion of brain- derived neurotrophic factor [BDNF], and the effect is separate from the blood pressure-lowering effect,” said study coauthor Ahmed Alhusban, a doctoral candidate at the university’s College of Pharmacy. “This will support a new area for treatments of stroke and other brain injury.”
The new research is the first to show that the positive effects of candesartan on blood-vessel growth in the brain are caused by BDNF. The researchers found that when candesartan blocks the angiotensin II type-1 (AT1) receptor, which lowers blood pressure, it stimulates the AT2 receptor (responsible for angiogenesis) and increases the secretion of BDNF, which encourages brain repair through the growth of new blood vessels.
“BDNF is a key player in learning and memory,” said research leader Professor Susan Fagan. “A reduction of BDNF in the brain has been associated with Alzheimer's disease and depression, so increasing this growth factor with a common medication is exciting.”
For the new study, the investigators treated both rat models and human brain cells with a low or high dose of angiotensin II alone or in combination with a dose of candesartan. Candesartan promoted angiogenesis, but this effect was prevented by blocking BDNF or by inactivating the AT2 receptor. This method identified the involvement of the AT2 receptor in BDNF secretion.
“This target is a key to enhance recovery and reduce the subsequent disability in stroke victims,” said Alhusban. “We know angiogenesis proteins are upregulated in the week after a brain injury. Stimulation of the AT2 receptor with a medication is likely to enhance this part of the brain's own recovery mechanisms.”
Drugs proven to “kick-start” BDNF will not only benefit stroke victims but could have a role in treating other brain injuries, particularly in veterans with combat-related traumatic brain damage.
The researchers estimate that it will take 5 to 10 years before drugs that activate the AT2 receptor as a mechanism for brain protection will be available to the public.
Source: University of Georgia; December 20, 2012.