The blockage of a tiny blood vessel in the brain can alter behaviour, even bringing on dementia and Alzheimer's in the long run, says a new finding.
"I am afraid that tiny strokes in our patients contribute -- over the long term -- to illness such as dementia and Alzheimer's," said Patrick D. Lyden, study co-author and head of neurology, Cedars-Sinai Medical Centre in Los Angeles.
"This data shows us, for the first time, that even a tiny stroke can lead to disability. Better tools will be required to tell whether human patients suffer memory effects from the smallest strokes," added Lyden, the journal Nature Neuroscience reports.
"It was surprising that blocking one small vessel could have a discernable impact on the behaviour of a rat," said Andy Y. Shih, who completed this work as a postdoctoral fellow in physics at the University of California, San Diego.
Working with rats, Shih, now assistant professor at the Medical University of South Carolina and colleagues, used laser light to clot blood at precise points within small blood vessels, according to a statement issued by the University of California, San Diego.
When they looked at the brains up to a week later, they saw tiny holes reminiscent of the widespread damage in the brains of dementia patients, as seen during autopsy.
These micro-lesions are too small to be detected with conventional MRI scans, which have a resolution of about a millimetre. Nearly two dozen of these small vessels enter the brain from a square mm of the brain surface.
"It's controversial whether that sort of damage has consequences, although the tide of evidence has been growing as human diagnostics improve," said David Kleinfeld, professor of physics and neurobiology, who led the research group.
To see whether such minute damage could change behaviour, the scientists trained thirsty rats to leap from one platform to another in the dark to get water.
The rats readily jump if they can reach the second platform with a paw or their snout, or stretch farther to touch it with their whiskers.
Many rats can be trained to rely on a single whisker if the others are clipped. If they can't feel the far platform, however, the rats will not budge.
"The whiskers line up in rows and each one is linked to a specific spot in the brain," Shih said. "By training them to use just one whisker, we were able to distill a behaviour down to a very small part of the brain."
FDA-approved drug memantine, prescribed to slow one aspect of memory decline associated with Alzheimer's disease, was found effective in making the rats more alert and active.
The brains of rats that received the drug found fewer signs of damage, and the rats were also better able to negotiate gaps.