Glial scars are permeable to the neurotoxic environment of chronic stroke infarcts

Another neuronal death cause your doctor should be working with researchers on. Or is your doctor going to do NOT ONE DAMN THING like usual? And your stroke president and board of directors are complicit in that incompetency.
https://www.sciencedirect.com/science/article/pii/S096999611830007X

Author links open overlay panelJacob C.Zbesko^aThuy-Vi V.Nguyen^abTaoYang^eJennifer BeischelFrye^aOmarHussain^aMeganHayes^aAmandaChung^aW. AnthonyDay^dKristinaStepanovic^aMajKrumberger^aJustineMona^aFrank M.Longo^eKristian P.Doyle^abc

https://doi.org/10.1016/j.nbd.2018.01.007Get rights and content

Open Access funded by National Institutes of Health

Under a Creative Commons license

open access

Highlights

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Liquefactive necrosis lasts for weeks following stroke.

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The extracellular fluid in areas of liquefactive necrosis is neurotoxic.

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Glial scars are permeable to the extracellular fluid present in areas of liquefactive necrosis.

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There is progressive neurodegeneration around areas of liquefactive necrosis after stroke.

Abstract

Following stroke, the damaged tissue undergoes liquefactive necrosis, a stage of infarct resolution that lasts for months although the exact length of time is currently unknown. One method of repair involves reactive astrocytes and microglia forming a glial scar to compartmentalize the area of liquefactive necrosis from the rest of the brain. The formation of the glial scar is a critical component of the healing response to stroke, as well as other central nervous system (CNS) injuries. The goal of this study was to evaluate the toxicity of the extracellular fluid present in areas of liquefactive necrosis and determine how effectively it is segregated from the remainder of the brain. To accomplish this goal, we used a mouse model of stroke in conjunction with an extracellular fluid toxicity assay, fluorescent and electron microscopy, immunostaining, tracer injections into the infarct, and multiplex immunoassays. We confirmed that the extracellular fluid present in areas of liquefactive necrosis following stroke is toxic to primary cortical and hippocampal neurons for at least 7 weeks following stroke, and discovered that although glial scars are robust physical and endocytic barriers, they are nevertheless permeable. We found that molecules present in the area of liquefactive necrosis can leak across the glial scar and are removed by a combination of paravascular clearance and microglial endocytosis in the adjacent tissue. Despite these mechanisms, there is delayed atrophy, cytotoxic edema, and neuron loss in regions adjacent to the infarct for weeks following stroke. These findings suggest that one mechanism of neurodegeneration following stroke is the failure of glial scars to impermeably segregate areas of liquefactive necrosis from surviving brain tissue.

Brain liquefaction after stroke is toxic to surviving brain: study

Well shit, another area needing followup, which will likely not occur until your grandchildren need it.  Do we need to aspirate this liquid from our brain? This one suggests 1/3 of stroke survivors get dementia. What the hell is your doctor doing to prevent that? ANYTHING AT ALL?
https://medicalxpress.com/news/2018-02-brain-liquefaction-toxic-surviving.html

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 brain tissue 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 stroke; 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 scar 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 fluid lasts. Liquefied brain tissue eventually will result in an empty cavity in which healthy brain tissue 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

Journal reference: Neurobiology of Disease

Provided by: University of Arizona