(Press-News.org)
Osaka, Japan – Ischemic stroke, caused by a blockage of blood flow to the brain, is a common cause of death and disability. Treatments are urgently needed to improve patient outcomes, because recovery currently depends largely on the timely injection of a blood clot-dissolving drug. Priorities for therapy include limiting inflammation at the ischemic site and rebuilding neuronal connections damaged by the stroke. However, a molecule that can achieve these therapeutic effects has remained elusive.
In a study to be published in Stroke, researchers from Osaka University provide new hope for patients. They have identified two proteins, R-spondin 3 (RSPO3) and LGR4, that trigger a cascade of reactions in cells (i.e., a signaling pathway) to reduce inflammation in the ischemic brain. RSPO3 and LGR4 also stimulate the growth of extensions from neurons, a process called neurite outgrowth.
“Previous studies showed that RSPO3 was beneficial in lung injuries caused by inflammation. We also knew that RSPO3 stimulates a signaling pathway, named the ‘canonical Wnt pathway’, that promotes neurite outgrowth,” explains Munehisa Shimamura, lead author of the study. “We wondered whether RSPO3 reduces inflammation and promotes neurite outgrowth after ischemic stroke.”
Previous studies have shown that RSPO3 and LGR4 are present in the same brain structures, and that RSPO3 activates LGR4 to stimulate the canonical Wnt pathway. The team from Osaka University localized RSPO3 in endothelial cells and LGR4 in microglia/macrophage cells and neurons in the ischemic brain.
“Because of this close localization, RSPO3 could act on LGR4,” explains Hironori Nakagami, a senior author of the study. “To test this hypothesis, we injected RSPO3 into the brains of mice 24 and 48 hours after ischemic stroke.”
Remarkably, nine days after the stroke, mice that were injected with RSPO3 exhibited fewer sensory and motor deficits than mice injected with a control protein. The expression of pro-inflammatory factors was reduced, whereas signs of neurite outgrowth increased. How? The researchers found that RSPO3/LGR4 decreased the expression of TLR4, which is one of proteins essential for inducing inflammation.
These findings are particularly exciting because RPSO3 was given to mice one day after the stroke, suggesting a potential benefit to treatments in later stages of stroke. Thus, targeting RSPO3/LGR4 signaling is a promising lead for developing new therapies for ischemic stroke and improving patient outcomes.
###
The article, “R-spondin 3/LGR4 axis is a novel inflammatory and neurite outgrowth signaling system in the ischemic brain in mice,” will be published in Stroke at DOI: https://doi.org/10.1161/STROKEAHA.122.041970
About Osaka University
Osaka University was founded in 1931 as one of the seven imperial universities of Japan and is now one of Japan's leading comprehensive universities with a broad disciplinary spectrum. This strength is coupled with a singular drive for innovation that extends throughout the scientific process, from fundamental research to the creation of applied technology with positive economic impacts. Its commitment to innovation has been recognized in Japan and around the world, being named Japan's most innovative university in 2015 (Reuters 2015 Top 100) and one of the most innovative institutions in the world in 2017 (Innovative Universities and the Nature Index Innovation 2017). Now, Osaka University is leveraging its role as a Designated National University Corporation selected by the Ministry of Education, Culture, Sports, Science and Technology to contribute to innovation for human welfare, sustainable development of society, and social transformation.
Website: https://resou.osaka-u.ac.jp/en
END
Astronomers have found that supermassive black holes obscured by dust are more likely to grow and release tremendous amounts of energy when they are inside galaxies that are expected to collide with a neighbouring galaxy. The new work, led by researchers from Newcastle University, is published in Monthly Notices of the Royal Astronomical Society.
Galaxies, including our own Milky Way, contain supermassive black holes at their centres. They have masses equivalent to millions, or even billions, times that of our ...
Rooftop solar arrays have the potential to meet the annual electricity demands of up to 35% of US manufacturing sectors.
On-site sources of renewable energy currently supply less than 0.1% of industrial electricity demand in the US.
The industrial sector accounts for 38% of global energy consumption and 37% of greenhouse gas emissions.
Despite having the potential to cover 13.6% of the national electricity demand, rooftop solar arrays currently account for just 2.2% of the electricity grid mix.
Mounted on the rooftops ...
Students in Sweden are positive towards AI tools such as ChatGPT in education, but 62 percent believe that using chatbots during exams is cheating. However, where the boundary for cheating lies is highly unclear. This is shown in a survey from Chalmers University of Technology, which is the first large-scale study in Europe to investigate students' attitudes towards artificial intelligence in higher education.
“I am afraid of AI and what it could mean for the future.”
“Don't worry so much! Keep up with the development and adapt your teaching ...
Shortages of health workers such as doctors, nurses and midwifery staff are strongly associated with higher death rates, especially for certain diseases such as neglected tropical diseases and malaria, pregnancy and birth complications, diabetes and kidney diseases, finds an analysis of 172 countries and territories, published by The BMJ today.
The results show that, although inequalities in health workforces have been decreasing globally over the past 30 years, they continue to have a substantial ...
Experts have called for further scrutiny of a new Pfizer vaccine given during pregnancy to prevent respiratory infection in infants, after trials of a similar GSK vaccine were stopped after a rise in preterm birth and infant deaths.
Pfizer says its vaccine is safe and effective, but experts contacted as part of an investigation published by The BMJ today, say Pfizer’s trial data should be reviewed in light of the signal for preterm births seen in GSK’s trial.
Pfizer’s ...
The silicon microchips of future quantum computers will be packed with millions, if not billions of qubits – the basic units of quantum information – to solve the greatest problems facing humanity. And with millions of qubits needing millions of wires in the microchip circuitry, it was always going to get cramped in there.
But now engineers at UNSW Sydney have made an important step towards solving a long-standing problem about giving their qubits more breathing space -- and it all revolves around jellybeans.
Not the kind we rely on for a sugar hit to get us past the 3pm slump. But jellybean quantum dots –elongated areas between qubit ...
Around one in five people may be suffering with obstructive sleep apnoea (OSA), according to a study published today (Thursday) in the ERJ Open Research [1].
People with OSA often snore loudly, their breathing starts and stops during the night, and they may wake up several times. Not only does this cause tiredness, but it can also increase the risk of high blood pressure, stroke, heart disease and type 2 diabetes.
Treatments and lifestyle changes can help people with OSA. However, ...
As the cost of living continues to spiral, a new report shows more than half of gig economy workers in the UK are paid below the minimum wage.
The first-of-its-kind study, led by the University of Bristol, found 52% of gig workers doing jobs ranging from data entry to food delivery were earning below the minimum wage. On average respondents were earning £8.97 per hour – around 15% below the current UK minimum wage, which rose to £10.42 this month.
More than three-quarters (76%) of survey respondents also experienced work-related ...
Sophia Antipolis, 11 May 2023: A healthy diet is associated with greater physical fitness in middle-aged adults, according to research published today in the European Journal of Preventive Cardiology, a journal of the European Society of Cardiology (ESC).1
“This study provides some of the strongest and most rigorous data thus far to support the connection that better diets may lead to higher fitness,” said study author Dr. Michael Mi of Beth Israel Deaconess Medical Center, Boston, US. “The improvement in fitness we observed in participants with better diets was similar to the effect of taking 4,000 more steps each ...
New research led by the universities of Southampton and Oxford has found that the risk of long COVID is strongly associated with area-level deprivation, with the odds of having long COVID 46 percent higher for people from the most deprived areas, compared to those in the least deprived areas.
Published in the Journal of the Royal Society of Medicine, the study analysed over 200,000 working-age adults and is the first to quantify the association between long COVID and socioeconomic status across a range of occupation sectors.
Analysing data from the Office ...
