Even the Smallest Possible Stroke Can Damage Brain Tissue and Impair Cognitive Function

Blocking a single tiny blood vessel in the brain can harm neural tissue and even alter behavior, a new study from the University of California, San Diego has shown. But these consequences can be mitigated by a drug already in use, suggesting treatment that could slow the progress of dementia associated with cumulative damage to miniscule blood vessels that feed brain cells. The team reports their results in the December 16 advance online edition of Nature Neuroscience.

"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," said Andy Y. Shih, lead author of the paper who completed this work as a postdoctoral fellow in physics at UC San Diego. Shih is now an assistant professor at the Medical University of South Carolina.

Working with rats, Shih and colleagues used laser light to clot blood at precise points within small blood vessels that dive from the surface of the brain to penetrate neural tissue. When they looked at the brains up to a week later, they saw tiny holes reminiscent of the widespread damage often seen when the brains of patients with dementia are examined as a part of an autopsy.

These micro-lesions are too small to be detected with conventional MRI scans, which have a resolution of about a millimeter. Nearly two dozen of these small vessels enter the brain from a square millimeter area of the surface of the brain.

"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 leads the research group.

To see whether such minute damage could change behavior, 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, but if they can’t feel the far platform, they won’t 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 behavior down to a very small part of the brain."

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 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," said Patrick D. Lyden, a co-author of the study and chair of the department of neurology at Cedars-Sinai Medical Center in Los Angeles. "I am afraid that tiny strokes in our patients contribute—over the long term—to illness such as dementia and Alzheimer’s disease," he said, adding that "better tools will be required to tell whether human patients suffer memory effects from the smallest strokes."

“We used powerful tools from biological physics, many developed in Kleinfeld’s laboratory at UC San Diego, to link stroke to dementia on the unprecedented small scale of single vessels and cells,” Shih said. “At my new position 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.”

Scientists Identify New Stem Cells with Therapeutic Potential

The discovery, published in the journal PLOS Biology, offers new opportunities in the treatment of cardiovascular diseases, cancer and many other diseases.

The growth of new blood vessels – angiogenesis – occurs during the repair of damaged tissue and organs in adults. However, malignant tumors also grow new blood vessels in order to receive oxygen and nutrients. As such, angiogenesis is both beneficial and detrimental to health, depending on the context, requiring therapeutic approaches that can either help to stimulate or prevent it. Therapeutics that aim to prevent the growth of new blood vessels are already in use, but the results are often more modest than predicted.

For more than a decade, Prof Petri Salvén of the University of Helsinki and his colleagues have studied the mechanisms of angiogenesis to discover how blood vessel growth could be prevented or accelerated effectively.

“We succeeded in isolating endothelial cells with a high rate of division in the blood vessel walls of mice. We found these same cells in human blood vessels and blood vessels growing in malignant tumors in humans. These cells are known as vascular endothelial stem cells. In a cell culture, one such cell is capable of producing tens of millions of new blood vessel wall cells,” Prof Salvén said.

From their studies in mice, the team was able to show that the growth of new blood vessels weakens, and the growth of malignant tumors slows, if the amount of these cells is below normal. Conversely, new blood vessels form where these stem cells are implanted.

Researchers from ETH Zurich have quite literally created a “cell phone”: they have reprogrammed mammalian cells in such a way that they can “phone” each other via chemical signals.

Telephoning is a mutual exchange of information: A phones B and they both agree what B should do. Once this is done, Party B phones Party A to let him or her know. A no longer phones B. During this two-way communication, electrical signals are sent, and for their transmission suitable devices are necessary.

Based on this formula, a team of bioengineers headed by Martin Fussenegger and Jörg Stelling at ETH Zurich’s Department of Biosystems Science and Engineering in Basel has programmed mammalian cells in such a way that two cells can communicate via chemical signals. The scientists have thus incorporated a synthetic two-way communication system into mammalian cells for the first time that also responds to concentration differences in the signal molecules. The researchers used suitable signal molecules and constructed “devices” out of biological components that receive, process and respond accordingly to the signals. The devices consist of suitable genes and their products, proteins, which are linked to each other logically.

Zebrafish Study Explains Why the Circadian Rhythm Affects Your Health

The circadian rhythm is regulated by a “clock” that reacts to both incoming light and genetic factors.

In an article now being published in the scientific journal Cell Reports, it is demonstrated for the first time that disruption of the circadian rhythm immediately inhibit blood vessel growth in zebra fish embryos.

During experiments with hours-old zebra fish embryos, the researchers manipulated their circadian rhythm through exposing them to lighting conditions varying from constant darkness to constant light. The growth of blood vessels in the various groups was then studied. The results showed that exposure to constant light (1800 lux) markedly impaired blood vessel growth; additionally, it affected the expression of genes that regulate the circadian clock.

"The results can definitely be translated into clinical circumstances. Individuals with disrupted circadian rhythms — for example, shift workers who work under artificial lights at night, people with sleeping disorders or a genetic predisposition — should be on guard against illnesses associated with disrupted blood vessel growth," says Lasse Dahl Jensen, researcher in Cardiovascular Physiology at Linköping University (LiU), and lead writer of the article.

Such diseases include heart attack, stroke, chronic inflammation, and cancer. Disruptions in blood vessel growth can also affect fetal development, women’s reproductive cycles, and the healing of wounds.

Scientists have found a way of growing new blood vessels inside the body. They used cells derived from skin, that when injected into a damaged leg in massive numbers, moulded into the shape of a small blood vessel. This improved blood supply to withered muscles, giving them a new lease of life.

The technique, developed at King’s College London, could also be used to repair the damage done by heart attacks. Professor Qingbo Xu, who is funded by the British Heart Foundation, started by taking human skin cells. Using a cocktail of genes and chemicals, he turned them into early-stage blood vessel cells, programmed to form blood vessels.

He then injected half a million of these cells into the hind leg of a mouse whose foot muscles had been damaged due to poor circulation. These formed a small blood vessel that ferried blood to the damaged muscle, allowing it to repair itself, enabling the creature to put some weight on its foot, the journal Proceedings of the National Academy of Sciences reports.

The professor hopes that injected into the heart, the same cells could be used to heal damage done by heart attacks.

A condition believed to be a normal part of the ageing process has been found to have a negative effect on the brain function of older adults.

Leukoaraiosis, also known as small vessel ischemia, is a condition in which diseased blood vessels lead to small areas of damage in the white matter of the brain. The lesions are common in the brains of people over the age of 60, although the amount of disease varies among individuals.

"We know that aging is a risk factor for leukoaraiosis, and we suspect that high blood pressure may also play a role, … Different systems of the brain respond differently to disease, … White matter damage affects connections within the brain’s language network, which leads to an overall reduction in network activity." -Kirk M. Welker, M.D., assistant professor of radiology in the College of Medicine at Mayo Clinic in Rochester, Minn.

(Source: medicalxpress.com)

3D-printed sugar network to help grow artificial liver

Researchers have moved a step closer to creating a synthetic liver, after a US team created a template for blood vessels to grow into, using sugar.

Scientists have long been experimenting with the 3D printing of cells and blood vessels, building up tissue structure layer by layer with artificial cells. But the synthetically engineered cells often die before the tissue is formed. The technology, in which a 3D printer uses sugar as its building material, could one day be used for transplants. The study appears in the journal Nature Materials.