December 17, 2012
Behavior Of Rats Can Be Altered By A Single Blocked Blood Vessel
redOrbit Staff & Wire Reports - Your Universe Online
While a blockage in even one tiny blood vessel in the brain can damage neural tissue and cause behavior changes, a drug already approved by the FDA to treat Alzheimer's disease could lessen the harmful effects, University of California, San Diego (UCSD) researchers have discovered.
Andy Shih, a postdoctoral fellow in physics at UCSD at the time of the study who is now an assistant professor at the Medical University of South Carolina (MUSC), and his colleagues used laser lights to clot blood at specific areas within small blood vessels in rats.
The blood vessels in question go from the brain's surface and penetrate neural tissue, and when they analyzed the rodents' brains up to a week after the clotting, they observed miniature holes similar to the type of damage found in the brains of human dementia patients during an autopsy. Those lesions are too small to be detected by typical MRI scans, as nearly two dozen of them enter the brain from a one square millimeter area of the surface.
"The brain is incredibly dense with vasculature. It was surprising that blocking one small vessel could have a discernable impact on the behavior of a rat," Shih explained in a December 16 statement.
"We used powerful tools from biological physics“¦to link stroke to dementia on the unprecedented small scale of single vessels and cells," he added. "At“¦ MUSC, I plan to work on ways to improve the detection of micro-lesions in human patients with MRI. This way clinicians may be able to diagnose and treat dementia earlier."
In a paper published Sunday in the online edition of the journal Nature Neuroscience, Shih and his co-authors describe how they tested whether or not minor damage to a single blood vessel could alter a rat's behavior.
They trained the creatures to leap from one platform to another to obtain water when thirsty -- a jump they will make easily is they are able to reach the second platform with their paw, snout, or even with a single whisker. However, they would not even attempt the feat if they could not feel the destination platform.
"When Shih blocked single microvessels feeding a column of brain cells that respond to signals from the remaining whisker, the rats still crossed to the far platform when the gap was small. But when it widened beyond the reach of their snouts, they quit," the university explained. "The FDA-approved drug memantine, prescribed to slow one aspect of memory decline associated with Alzheimer's disease, ameliorated these effects. Rats that received the drug jumped whisker-wide gaps, and their brains showed fewer signs of damage."
"This data shows us, for the first time, that even a tiny stroke can lead to disability," added co-author Patrick Lyden, chairman of the Cedars-Sinai Medical Center's Department of Neurology. "I am afraid that tiny strokes in our patients contribute -- over the long term -- to illness such as dementia and Alzheimer's disease“¦ better tools will be required to tell whether human patients suffer memory effects from the smallest strokes."