CDC/Blaine Mathison // Public Domain
CDC/Blaine Mathison // Public Domain

Nitric Oxide May Protect the Blood-Brain Barrier During Parasite Invasions

CDC/Blaine Mathison // Public Domain
CDC/Blaine Mathison // Public Domain

Illnesses brought on by invasive parasites are especially dangerous because of their ability to cross the nearly impenetrable blood-brain barrier (BBB). Resulting invasion can cause life-threatening inflammation of the brain and the central nervous system. Researchers at the Karolinksa Institute in Stockholm, Sweden studying African trypanosomiasis, or “sleeping sickness”—so named because the illness causes disruption of sleep patterns, among other, more dangerous symptoms—have discovered that nitric oxide (NO) can help maintain the integrity of the BBB, potentially reducing neurological damage. Their results were published in PLOS Pathogens.

Sleeping sickness is considered a “neglected disease,” Martin Rottenberg, professor of infection and immunity at Karolinksa Institute, tells mental_floss. That's the case even though we have made steady progress against it in recent years; in 2014, it affected just 3796 people in 36 sub-Saharan African countries—the first time the number of annual infections dropped below 10,000 in 80 years.

Sleeping sickness is transmitted to humans by the bite of an infected tsetse fly. “The parasite disseminates and replicates in the blood, and somehow it penetrates the brain," Rottenberg describes. "The brain is a protected organ, with a very tight barrier, so we wanted to understand how the barrier was opening and closing.”

They hypothesized that NO, which is produced in response to inflammation and infection in the body, might have a protective effect on the blood-brain barrier. They decided to test this theory using mice they had infected with sleeping sickness. What they found was a mixed bag: on the one hand, the parasite generates an immune response that increases permeability of the blood vessels of the BBB and makes an animal more susceptible to infection. “This immune response is meant to control the parasite, but it also helps it into the brain,” Rottenberg says. On the other hand, it produces nitric oxide, “which puts a brake on the parasites so the infection and disease have a much slower pace in the presence of NO."

Then they created mutant mice that lack the enzyme iNOS, the precursor to NO, and infected them with sleeping sickness. They found that these mice had greater numbers of parasites and host immune cells in their brains. This confirmed their theory that nitric oxide is necessary to fight these infections. Further study revealed that an inflammatory cytokine called tumor necrosis factor (TNF) may be responsible for inhibiting the production of NO.

Further research could attempt to reduce neural inflammation by administering nitric oxide somehow, though that is going to take some time to perfect. According to Rottenberg, “It’s a complicated molecule because it reacts very fast with other molecules, it’s very unstable, and in the case of inflammation that has been linked to damage." 

In the meantime, the researchers found that an antibiotic called minocycline can restore the BBB in mice that lack the iNOS enzyme, and reduce inflammation and parasite numbers in the brain. “I think this can help to treat the sickness a little sooner,” Rottenberg says. 

Jamie McCarthy/Getty Images for Bill & Melinda Gates Foundation
Bill Gates is Spending $100 Million to Find a Cure for Alzheimer's
Jamie McCarthy/Getty Images for Bill & Melinda Gates Foundation
Jamie McCarthy/Getty Images for Bill & Melinda Gates Foundation

Not everyone who's blessed with a long life will remember it. Individuals who live into their mid-80s have a nearly 50 percent chance of developing Alzheimer's, and scientists still haven't discovered any groundbreaking treatments for the neurodegenerative disease [PDF]. To pave the way for a cure, Microsoft co-founder and philanthropist Bill Gates has announced that he's donating $100 million to dementia research, according to Newsweek.

On his blog, Gates explained that Alzheimer's disease places a financial burden on both families and healthcare systems alike. "This is something that governments all over the world need to be thinking about," he wrote, "including in low- and middle-income countries where life expectancies are catching up to the global average and the number of people with dementia is on the rise."

Gates's interest in Alzheimer's is both pragmatic and personal. "This is something I know a lot about, because men in my family have suffered from Alzheimer’s," he said. "I know how awful it is to watch people you love struggle as the disease robs them of their mental capacity, and there is nothing you can do about it. It feels a lot like you're experiencing a gradual death of the person that you knew."

Experts still haven't figured out quite what causes Alzheimer's, how it progresses, and why certain people are more prone to it than others. Gates believes that important breakthroughs will occur if scientists can understand the condition's etiology (or cause), create better drugs, develop techniques for early detection and diagnosis, and make it easier for patients to enroll in clinical trials, he said.

Gates plans to donate $50 million to the Dementia Discovery Fund, a venture capital fund that supports Alzheimer's research and treatment developments. The rest will go to research startups, Reuters reports.

[h/t Newsweek]

A New Analysis of Chopin's Heart Reveals the Cause of His Death

For years, experts and music lovers alike have speculated over what caused celebrated composer Frederic Chopin to die at the tragically young age of 39. Following a recent examination of his heart, Polish scientists have concluded that Chopin succumbed to tuberculosis, just as his death certificate states, according to The New York Times.

When Chopin died in 1849, his body was buried in Paris, where he had lived, while his heart was transported to his home city of Warsaw, Poland. Chopin—who appeared to have been ill with tuberculosis (TB)—was terrified of the prospect of being buried alive, and nostalgic for his national roots. He asked for his heart to be cut out, and his sister later smuggled it past foreign guards and into what is now Poland.

Preserved in alcohol—likely cognac—and stored in a crystal jar, Chopin's heart was laid to rest inside Holy Cross Church in Warsaw. (It was removed by the Germans in 1944 during the Warsaw Uprising, and later returned.) But rumors began to swirl, as the same doctor tasked with removing the heart had also conducted an autopsy on the composer's body, according to the BBC.

The physician's original notes have been lost, but it's said he concluded that Chopin had died not from TB but from "a disease not previously encountered." This triggered some scholars to theorize that Chopin had died from cystic fibrosis, or even a form of emphysema, as the sickly musician suffered from chronic respiratory issues. Another suspected condition was mitral stenosis, or a narrowing of the heart valves.

Adhering to the wishes of a living relative, the Polish church and government have refused to let scientists conduct genetic tests on Chopin's heart. But over the years, teams have periodically checked up on the organ to ensure it remains in good condition, including once in 1945.

In 2014, a group of Chopin enthusiasts—including Polish scientists, religious officials, and members of the Chopin Institute, which researches and promotes Chopin's legacy—were given the go-ahead to hold a clandestine evening meeting at Holy Cross Church. There, they removed Chopin's heart from its perch inside a stone pillar to inspect it for the first time in nearly 70 years.

Fearing the jar's alcohol would evaporate, the group added hot wax to its seal and took more than 1000 photos of its contents. Pictures of the surreptitious evening procedure weren't publicly released, but were shown to the AP, which described Chopin's preserved heart as "an enlarged white lump."

It's unclear what prompted a follow-up investigation on Chopin's heart, or who allowed it, but an early version of an article in the American Journal of Medicine states that experts—who did not open the jar—have newly observed that the famed organ is "massively enlarged and floppy," with lesions and a white, frosted appearance. These observations have prompted them to diagnose the musician's cause of death as pericarditis, which is an inflammation of tissue around the heart. This likely stemmed from his tuberculosis, they said.

Some scientists might still clamor at the prospect of testing tissue samples of Chopin's heart. But Michael Witt of the Polish Academy of Sciences—who was involved in this latest examination—told The Guardian that it was unnecessary to disturb what many consider to be a symbol of national pride.

"Some people still want to open it in order to take tissue samples to do DNA tests to support their ideas that Chopin had some kind of genetic condition," Witt said. "That would be absolutely wrong. It could destroy the heart, and in any case, I am quite sure we now know what killed Chopin."

[h/t The New York Times]


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