Biomaterial developed at UCLA helps regrow brain tissue after stroke in mice

by Leigh Hopper

Tnew stroke-healing gel created by UCLA researchers helped regrow neurons and blood vessels in mice whose brains had been damaged by strokes. The finding is reported May 21 in Nature Materials.

“We tested this in laboratory mice to determine if it would repair the brain and lead to recovery in a model of stroke,” said Dr. S. Thomas Carmichael, professor of neurology at the David Geffen School of Medicine at UCLA. “The study indicated that new brain tissue can be regenerated in what was previously just an inactive brain scar after stroke.”

The results suggest that such an approach could some day be used to treat people who have had a stroke, said Tatiana Segura, a former professor of chemical and biomolecular engineering at UCLA who collaborated on the research. Segura is now a professor at Duke University.

The brain has a limited capacity for recovery after stroke. Unlike the liver, skin and some other organs, the brain does not regenerate new connections, blood vessels or tissue structures after it is damaged. Instead, dead brain tissue is absorbed, which leaves a cavity devoid of blood vessels, neurons or axons — the thin nerve fibers that project from neurons.

To see if healthy tissue surrounding the cavity could be coaxed into healing the stroke injury, Segura engineered a hydrogel that, when injected into the cavity, thickens to create a scaffolding into which blood vessels and neurons can grow. The gel is infused with medications that stimulate blood vessel growth and suppress inflammation, since inflammation results in scars and impedes functional tissue from regrowing.

After 16 weeks, the stroke cavities contained regenerated brain tissue, including new neuronal connections — a result that had not been seen before. The mice’s ability to reach for food improved, a sign of improved motor behavior, although the exact mechanism for the improvement wasn’t clear.

“The new axons could actually be working,” Segura said. “Or the new tissue could be improving the performance of the surrounding, unharmed brain tissue.”

The gel was eventually absorbed by the body, leaving behind only new tissue.

The research was designed to explore recovery in acute stroke, the period immediately following a stroke — in mice, that period lasts five days; in humans, it’s two months. Next, Carmichael and Segura plan to investigate whether brain tissue can be regenerated in mice long after the stroke injury. More than 6 million Americans are living with long-term effects of stroke, which is known as chronic stroke.

The other authors of the paper are Lina Nih and Shiva Gojgini, both of UCLA.

The study was supported by the National Institutes of Health.

http://newsroom.ucla.edu/releases/biomaterial-ucla-regrow-brain-tissue-after-stroke-mice

Keeping gut bacteria in balance could help delay age-related diseases

Why do some people remain healthy into their 80s and beyond, while others age faster and suffer serious diseases decades earlier? New research led by UCLA life scientists may produce a new way to answer that question—and an approach that could help delay declines in health.

Specifically, the study suggests that analyzing intestinal bacteria could be a promising way to predict health outcomes as we age.

The researchers discovered changes within intestinal microbes that precede and predict the death of fruit flies. The findings were published in the open-source journal Cell Reports.

“Age-onset decline is very tightly linked to changes within the community of gut microbes,” said David Walker, a UCLA professor of integrative biology and physiology, and senior author of the research. “With age, the number of bacterial cells increase substantially and the composition of bacterial groups changes.”

The study used fruit flies in part because although their typical life span is just eight weeks, some live to the age equivalent of humans’ 80s and 90s, while others age and die much younger. In addition, scientists have identified all of the fruit fly’s genes and know how to switch individual ones on and off.

In a previous study, the UCLA researchers discovered that five or six days before flies died, their intestinal tracts became more permeable and started leaking.

In the latest research, which analyzed more than 10,000 female flies, the scientists found that they were able to detect bacterial changes in the intestine before the leaking began. As part of the study, some fruit flies were given antibiotics that significantly reduce bacterial levels in the intestine; the study found that the antibiotics prevented the age-related increase in bacteria levels and improved intestinal function during aging.

The biologists also showed that reducing bacterial levels in old flies can significantly prolong their life span.

“When we prevented the changes in the intestinal microbiota that were linked to the flies’ imminent death by feeding them antibiotics, we dramatically extended their lives and improved their health,” Walker said. (Microbiota are the bacteria and other microorganisms that are abundant in humans, other mammals, fruit flies and many other animals.)

Flies with leaky intestines that were given antibiotics lived an average of 20 days after the leaking began—a substantial part of the animal’s life span. On average, flies with leaky intestines that did not receive antibiotics died within a week.

The intestine acts as a barrier to protect our organs and tissue from environmental damage.

“The health of the intestine—in particular the maintenance of the barrier protecting the rest of the body from the contents of the gut—is very important and might break down with aging,” said Rebecca Clark, the study’s lead author. Clark was a UCLA postdoctoral scholar when the research was conducted and is now a lecturer at England’s Durham University.

The biologists collaborated with William Ja, an assistant professor at Florida’s Scripps Research Institute, and Ryuichi Yamada, a postdoctoral research associate in Ja’s laboratory, to produce an additional group of flies that were completely germ-free, with no intestinal microbes. Those flies showed a very dramatic delay in intestinal damage, and they lived for about 80 days, approximately one-and-a-half times as long as the animal’s typical life span.

Scientists have recently begun to connect a wide variety of diseases, including diabetes and Parkinson’s, among many others, to changes in the microbiota, but they do not yet know exactly what healthy microbiota look like.

“One of the big questions in the biology of aging relates to the large variation in how we age and how long we live,” said Walker, who added that scientific interest in intestinal microbes has exploded in the last five years.

When a fruit fly’s intestine begins to leak, its immune response increases substantially and chronically throughout its body. Chronic immune activation is linked with age-related diseases in people as well, Walker said.

Walker said that the study could lead to realistic ways for scientists to intervene in the aging process and delay the onset of Parkinson’s disease, Alzheimer’s disease, cancer, stroke, cardiovascular disease, diabetes and other diseases of aging—although such progress could take many years, he said.