Brain liquefaction after stroke is toxic to surviving brain: study

February 20, 2018, University of Arizona
UA study: Brain liquefaction after stroke is toxic to surviving brain
A time-lapse showing dye injected into a damaged area of the mouse brain seven weeks post-stroke (upper left corner). The dye has spread past the glial scar barrier after six and 12 hours of injection. Credit: Kristian Doyle, Ph.D. / UA College of Medicine - Tucson.

Scientists have known for years that the brain liquefies after a stroke. If cut off from blood and oxygen for a long enough period, a portion of the brain will die, slowly morphing from a hard, rubbery substance into liquid goop.

Now, researchers at the University of Arizona College of Medicine - Tucson have discovered that this liquefied, dying is toxic—and can slowly leak into the remaining healthy portion of the brain, potentially causing harm. The new findings may open the door for developing new treatments to ward off dementia after ; they are described in the April 2018 issue of Neurobiology of Disease.

"Most people probably assume that the brain heals in the same way as other tissues," said Kristian Doyle, PhD, an assistant professor in the UA Department of Immunobiology. "But it doesn't; dead brain tissue doesn't just heal and go away like other bodily injuries. Instead it liquefies and remains in this liquefactive state for a long time."

To better understand this dying fluid, Dr. Doyle and his laboratory team studied mice that had experienced strokes. First, the researchers extracted fluid from the area of liquefaction and tested its toxicity by placing it in a petri dish with living neurons. After four hours, more than 50 percent of the neurons in the dish had died, compared to neurons that were placed in a dish with regular, healthy brain fluid.

The researchers then evaluated how well this toxic fluid was sealed off from the surviving brain.

Normally, a forms around dying brain tissue after a stroke. This scar, known as a glial scar, creates a barrier around the injured area to protect the remaining brain; it's formation is critical to the healing process.

Using a high-powered microscope, the UA researchers imaged this barrier between the healthy and injured portions of the mouse brain. Up close, the glial scar looked like "a fence made of branches twisted tightly together," Dr. Doyle said.

Then they injected a dye into the injured portion of the brain. At seven weeks post-stroke, the dye was able to spread past the glial scar and into the healthy brain region. According to Dr. Doyle, this suggested that toxic substances present in the liquefied tissue also leak into the brain after a stroke, potentially killing healthy neurons.

"We found that the glial scar is a pretty decent barrier, but it's not perfect," Dr. Doyle said. "Imagine putting sandbags around your house; they will reduce flood damage, but not control everything."

Dr. Doyle suspects this slow, leaking fluid may be a cause of dementia after stroke. Of the 10 million people who survive a stroke each year, about one-third will develop dementia for unclear reasons, he said.

If the brain is injured near the hippocampus—the portion of the brain responsible for memory—perhaps this slow leak of toxic fluid causes neurodegeneration, the loss of neurons in the brain, and ultimately, memory problems.

"This work really challenges the old paradigms and breaks new ground critical for our understanding of stroke and its consequences," said Janko Nikolich-Zugich, MD, PhD, chair of the UA Department of Immunobiology. "We used to think that the glial scar forms a fool-proof barrier, and had no idea about the toxicity of the liquefied brain materials. Thanks to this research, we now will be able to consider new and different stroke therapies."

Nevertheless, further research is needed. The team hopes to verify its results in the future by showing that post-stroke memory problems can be curbed with a drug that makes the glial scar's barrier more robust.

Research also is needed to find out precisely how long the toxic lasts. Liquefied brain tissue eventually will result in an empty cavity in which healthy once existed. Dr. Doyle's lab believes that the liquefied tissue lasts for months in the brain before the process is complete.

Explore further: Eye could provide 'window to the brain' after stroke

Related Stories

Eye could provide 'window to the brain' after stroke

February 7, 2018
Research into curious bright spots in the eyes on stroke patients' brain images could one day alter the way these individuals are assessed and treated. A team of scientists at the National Institutes of Health found that ...

First evidence of ischemia-induced multipotent stem cells in post-stroke human brain

May 3, 2017
Researchers have shown that following a stroke-induced ischemic injury to the human brain, stem cells are produced that have the potential to differentiate and mature to form neurons that can help repair the damage to the ...

Unexpected cell repairs injured spinal cord

July 7, 2011
Lesions to the brain or spinal cord rarely heal fully, which leads to permanent functional impairment. After injury to the central nervous system (CNS), neurons are lost and largely replaced by a scar often referred to as ...

Researchers discover cause of brain sensitivity to lack of oxygen

October 30, 2017
Researchers at Maastricht University Medical Center and Maastricht University have discovered why the brain is more sensitive to oxygen deprivation, or hypoxia, than other organs. Hypoxia caused by a stroke, for example, ...

Transplanted neurons incorporated into a stroke-injured rat brain

January 23, 2017
Today, a stroke usually leads to permanent disability – but in the future, the stroke-injured brain could be reparable by replacing dead cells with new, healthy neurons, using transplantation. Researchers at Lund University ...

Modifying scar tissue can potentially improve outcome in chronic stroke

May 21, 2012
New research from the Buck Institute for Research on Aging shows that modifying the scar tissue that develops following a stroke is a promising avenue for future treatments. The need for therapeutics for chronic stroke is ...

Recommended for you

New technique helps uncover changes in ALS neurons

June 22, 2018
Northwestern Medicine scientists have discovered that some neurons affected by amyotrophic lateral sclerosis (ALS) display hypo-excitability, using a new method to measure electrical activity in cells, according to a study ...

Broken shuttle may interfere with learning in major brain disorders

June 22, 2018
Unable to carry signals based on sights and sounds to the genes that record memories, a broken shuttle protein may hinder learning in patients with intellectual disability, schizophrenia, and autism.

Watching stem cells repair spinal cord in real time

June 22, 2018
Monash University researchers have restored movement and regenerated nerves using stem cells in zebra fish where the spinal cord is severely damaged.

Scientists discover fundamental rule of brain plasticity

June 21, 2018
Our brains are famously flexible, or "plastic," because neurons can do new things by forging new or stronger connections with other neurons. But if some connections strengthen, neuroscientists have reasoned, neurons must ...

Waking up is hard to do: Prefrontal cortex implicated in consciousness

June 21, 2018
Philosophers have pondered the nature of consciousness for thousands of years. In the 21st century, the debate over how the brain gives rise to our everyday experience continues to puzzle scientists. To help, researchers ...

Researchers find mechanism behind choosing alcohol over healthy rewards

June 21, 2018
A new study links molecular changes in the brain to behaviours that are central in addiction, such as choosing a drug over alternative rewards. The researchers have developed a method in which rats learn to get an alcohol ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.