An ischemic stroke is caused by a blockage of blood flow to the brain and is the most common type of stroke. An intracerebral hemorrhage is caused by bleeding in the brain.

“Our study suggests that higher estrogen levels due to a number of reproductive factors, including a longer reproductive life span and using hormone therapy or contraceptives, are linked to a lower risk of ischemic stroke and intracerebral hemorrhage,” said study author Peige Song, PhD, of the Zhejiang University School of Medicine in Hangzhou, China. “These findings might help with new ideas for stroke prevention, such as considering screenings for people who have a short lifetime exposure to estrogen.”

The study involved 122,939 postmenopausal female participants with a median age of 58 living in China without stroke at the start of the study.

Participants answered questions on personal factors, such as age, sex, and occupation, as well as lifestyle factors, such as smoking, alcohol use, exercise and medical history. They also answered questions on reproductive health information, including age at first menstruation and start of menopause, number of pregnancies and miscarriages and oral contraceptive use.

Researchers looked at health insurance and disease registry data to determine which participants had a stroke. During an average follow-up period of nine years, 15,139 had a stroke. Of those,12,853 had ischemic stroke, 2,580 had intracerebral hemorrhage and 269 had subarachnoid hemorrhage, which is bleeding between the brain and the membrane that covers it.

Participants were divided into four groups determined by their reproductive life span, the number of years from first menstruation to menopause. Participants in the group with the shortest reproductive life span had up to 31 reproductive years. Participants in the group with the longest reproductive lifespan had 36 reproductive years or more.

As a percentage, participants in the longest group had slightly more strokes than those in the shortest group, 13.2% compared to 12.6%. But when researchers adjusted for other factors that could affect stroke risk, such as age, smoking, physical activity and high blood pressure, they found that participants in the longest group had a 5% lower risk of all kinds of stroke.

When looking at different types of stroke, female participants with the longest reproductive life span had a 5% lower risk of ischemic stroke and a 13% lower risk of intracerebral hemorrhage when compared to women with the shortest reproductive life span.

Researchers also looked at other factors affecting estrogen levels, such as number of births and use of oral contraceptives, both of which are associated with higher levels, and length of breastfeeding, which is associated with lower levels based on the hypothesis that pregnancy and oral contraceptive use represent relatively higher sustained blood estrogen levels. They found that higher estrogen levels led to a lower risk of all types of stroke, as well as ischemic stroke and intracerebral hemorrhage.

“Estrogen exposure throughout life could potentially be a useful indicator of a person’s risk of different types of stroke following menopause,” said Song. “However, more research is needed on the biological, behavioral, and social factors that may contribute to the link between estrogen exposure and stroke risk across a woman’s lifespan.”

A limitation of the study was that information on reproductive factors was collected mainly based on participants’ ability to recall events, and participants may not have remembered such events correctly.

Multiple sclerosis is an autoimmune disease in which the myelin, or fatty lining of nerve cells, is eroded, leading to nerve damage and slower signalling between the brain and the body. MS symptoms range from blurred vision to complete paralysis, and while there are treatments, the causes are not fully understood and nothing exists to reverse the disease process. More than 90,000 Canadians live with MS, according to the MS Society.

In new research published in Stem Cell Reports, Anastassia Voronova, an assistant professor and Canada Research Chair in Neural Stem Cell Biology, injected fractalkine into mice with chemically induced MS.

She found the treatment increased the number of new oligodendrocytes — vital brain and spinal cord cells that produce myelin in both embryonic and adult brains — which are damaged during the MS autoimmune attack.

“If we can replace those lost or damaged oligodendrocytes, then they could make new myelin and it is believed that would halt the disease progression, or maybe even reverse some of the symptoms,” Voronova says. “That’s the Holy Grail in the research community and something that we’re very passionate about.”

Voronova’s earlier research tested the safety and efficacy of fractalkine in normal mice and found similar beneficial effects. Other researchers have demonstrated that fractalkine may provide protection for nerves in mouse models before the disease is induced, but this is the first time it has been tested on animals that already have the disease.

Voronova and her team observed new oligodendrocytes, as well as reactivated progenitor cells that can regenerate oligodendrocytes, in the brains of the treated animals. Remyelination occurred in both the white and grey matter. The researchers also observed a reduction in inflammation, part of the damage caused by the immune system. Next steps for the treatment include testing it in other diseased mouse models, including those with neurodegenerative diseases other than MS.

The study, begun in 2001 and published this month in the Journal of the American College of Cardiology, analyzed brain imaging data from 270 full-term UCSF and BCCH newborns with congenital heart disease (CHD) for changes in brain injuries before and after newborn cardiac surgery. The scientists confirmed that recent advances in surgical and clinical care that maintain a higher postoperative blood pressure resulted in reducing brain injuries and better chances of patient survival.

“We were surprised to find that advances in care over the past 7 years resulted in a clear decline in brain injury linked to increasing the patient’s blood pressure following surgery,” said Shabnam Peyvandi, MD, lead author and pediatric cardiologist for UCSF Benioff Children’s Hospitals. “With advances in cardiac therapy and outcomes, our focus now is helping these children thrive.”

CHD, which refers to one or more abnormalities of an infant’s heart, impacts 40,000 newborns a year in the U.S. It is the most common newborn birth defect. About 1 in 4 of these infants have critical CHD and require surgery in the first month to first year of life. Heart abnormalities include improperly functioning heart valves, a hole in the muscular wall separating the heart chambers, and malformations in the heart’s blood vessels, which can result in altered patterns of blood flow. These anomalies reduce the flow of oxygen and nutrients to the brain and organs before birth, and can contribute to lifelong neurological and developmental disorders.

New Approaches to Monitor Brain Health

To monitor infant brain health for the study, UCSF and BCCH scientists used advanced magnetic resonance (MRI) brain imaging before and after heart surgery and consistently as the patient aged. The data was divided into four sequential stages, each containing five consecutive years of data. In the fourth and final stage, which ran from 2016 to 2021, infants were maintained at higher post-surgical blood pressures than in previous groups. This resulted in an almost 20% reduction in post-surgical brain injuries compared to the first group in 2001.

During the course of this study, Peyvandi and the UCSF Benioff Children’s Hospitals Pediatric Heart Center published multiple articles investigating brain development and white matter injuries — including a link between moderate-severe white matter injuries that led to delays in childhood motor function — that opened the door to improving long term developmental outcomes by decreasing early brain injuries.

“Taken together, these findings underscore the importance of tracking brain injury and implementing changes to reduce occurrences that will improve outcomes,” said Patrick McQuillen, MD, senior author and professor of Pediatrics, UCSF Benioff Children’s Hospitals. “Based on this research and others, several leading heart centers have incorporated brain imaging into routine clinical practice.”

Work from this group has directly informed the creation of novel clinical programs to monitor and protect the brain in fetuses, newborns and children with CHD, including the Healthy Hearts & Minds Program and the Neonatal Cardiovascular Center of Excellence Growth and Neurodevelopment (GRAND) program that incorporates developmental care on the inpatient setting for newborns with critical CHD.

Other UCSF authors include Duan Xu, PHD, A. James Barkovich, MD, Dawn Gano, MD, MAS, V. Mohan Reddy, MD

The researchers hope to turn this discovery into viable treatment for some types of antibiotic-resistant infections. Antibiotic-resistant infections kill more than a million people globally each year.

For centuries, silver has been known to have antimicrobial properties. However, silver nanoparticles — microscopic spheres of silver small enough to operate at the cellular level — represent a new frontier in using the precious metal to fight bacteria.

In this study, the research team tested whether commercially available silver nanoparticles boost the power of antibiotics and enable these drugs to counter the very bacteria that have evolved to withstand them.

“We found that the silver nanoparticles and a common class of broad-spectrum antibiotics called aminoglycosides work together synergistically,” said Daniel Czyż, senior author of the study and an assistant professor in the UF/IFAS department of microbiology and cell science.

“When combined with a small amount of silver nanoparticles, the amount of antibiotic needed to inhibit the bacteria decreased 22-fold, which tells us that the nanoparticles make the drug much more potent,” Czyż explained. “In addition, aminoglycosides can have negative side effects, so using silver nanoparticles could allow for a lower dose of antibiotic, reducing those side effects.”

The findings were both surprising and exciting, said Autumn Dove, first author of the study and a doctoral candidate studying microbiology and cell science in the UF/IFAS College of Agricultural and Life Sciences.

“When I first saw the result, my first thoughts were, ‘Wow, this works!'” said Dove.

Over the last several decades, overuse of antibiotics had led to the emergence of antibiotic-resistant bacteria and a decline in the effectiveness of traditional antibiotic drugs, the researchers said. The study’s findings indicate that silver nanoparticles have the potential to renew the effectiveness of some of these drugs.

“Let’s say you get a bad burn on your hand, and it gets infected with one of these resistant strains of bacteria,” Dove said. “It’s possible that dressing that burn with a combination of silver nanoparticles and antibiotics could both clear that infection and prevent those resistant bacteria from spreading elsewhere.”

Though antibiotics mainly target bacteria, they can also damage human and animal cells. Using a microscopic worm called C. elegans, the researchers confirmed that the silver nanoparticles did not also make the antibiotic more toxic to non-bacterial cells.

Building off the study’s promising findings, the scientists next plan to seek FDA authorization for clinical trials and work with UF Innovate to patent an antimicrobial product that uses silver nanoparticles.

The silver nanoparticles used in the study were manufactured by the Natural Immunogenics Corporation, which helped fund the study through the UF Industry Partnerships Matching Grant Program. This program pairs UF researchers with Florida-based technology and energy companies to research and develop new products.

Funded by the U.S. Department of Defense’s Operational Energy Capability Improvement Fund (OECIF), the NREL research was done for the Air Force Research Laboratory (AFRL) to develop low-cost innovative energy sources for powering the armed forces worldwide.

The research is the latest effort to determine the effectiveness of perovskites for use in space applications, where it would be exposed to protons, alpha particles, atomic oxygen, and other stressors. The ability to use perovskites to generate power in space is enticing because they offer a lower-cost and lightweight option to other technologies with the potential for achieving efficiencies similar to those of current space PV technologies.

Just as on Earth, perovskite solar cells need to have suitable durability. However, the environment in space is significantly different. While the biggest challenges on Earth are related to weather, in space perovskites must address the problems that come from radiation bombardment and extreme temperature swings. Perovskites show signs of better tolerance to radiation than many other solar cells, but plenty of testing remains to be conducted.

Researchers last year ran simulations to demonstrate how exposure to radiation in space would affect perovskites. They determined the next-generation technology would work in space but pointed out the need to encapsulate the cell in some way to provide added protection.

In the follow-up research, Ahmad Kirmani, lead author of the latest Nature Energy paper, said simulations demonstrated a micron-thick layer of silicon oxide would preserve the efficiency and increase the lifetime of perovskite solar cells in space. As a comparison, the micron-thick layer is about 100 times thinner than a typical human hair.

Kirmani said the silicon oxide layer could reduce the weight of conventional radiation barriers used for other solar cells by more than 99% and serves as a first step toward designing lightweight and low-cost packaging for perovskites.

High-energy protons travel through perovskite solar cells without causing much harm. Low-energy protons, however, are more abundant in space and wreak more havoc on perovskite cells by knocking atoms out of place and causing efficiency levels to steadily decline. The lower energy protons interact with matter much more readily and the addition of the silicon oxide layer protected the perovskite from damage even from the low-energy protons.

“We thought it would be impossible for the silicon oxide to provide protection against fully penetrating long-range particles such as the high-energy protons and alpha particles,” Kirmani said. “However, the oxide layer turned out to be a surprisingly good barrier against those as well.”

The results are detailed in the paper “Metal oxide barrier layers for terrestrial and space perovskite photovoltaics.” The co-authors are David Ostrowski, Kaitlyn VanSant, Rosemary Bramante, Karen Heinselman, Jinhui Tong, Bart Stevens, William Nemeth, Kai Zhu, and Joseph Luther, from NREL; and several key collaborators who work with the team from the University of North Texas and the University of Oklahoma. VanSant holds the unique position of being a postdoctoral researcher at NASA who conducts research at NREL.

Exposure to a stream of low-energy protons caused unprotected perovskite solar cells to lose only about 15% of their initial efficiency, the researchers found. A larger concentration of particles destroyed the cells, while the protected perovskites demonstrated what the scientists described as “a remarkable resilience.” With the simple barrier, the cells showed no damage.

In addition to making the cells more resilient in space, the researchers also tested how the barrier could provide benefit in more conventional applications. They then exposed the perovskite solar cells to an uncontrolled moisture and temperature environment for several days to mimic storage conditions. The protected cells retained their initial 19% efficiency, while the unprotected cells showed significant degradation, from 19.4% to 10.8%. The oxide layer also provided protection when other perovskite compositions typically more sensitive to moisture were exposed to water.

Further, the perovskite solar cells were subjected to a test chamber where they were bombarded with ultraviolet photons similar to the environment at low-Earth orbit. The photons interacted with oxygen to create atomic oxygen. The unprotected cells were destroyed after eight minutes. The protected cells retained their initial efficiency after 20 minutes and only had a slight drop after 30 minutes.

The simulations and experiments revealed that by reducing the damage from radiation, the lifetime of the protected solar cells used in Earth’s orbits and deep space would be increased from months to years.

“Power conversion efficiency and operational stability of perovskite solar cells have been the two primary focus areas for the community so far,” he said. “We have made a lot of progress and I think we have come far to the point that we might be pretty close to hitting those targets needed for industrialization. However, to really enable this market entry, packaging is the next target.”

Because perovskite solar cells can be deposited onto a flexible substrate, the emerging technology, coupled with the protective layer of silicon oxide, allows its use for various terrestrial applications such as powering drones.

NREL is the U.S. Department of Energy’s primary national laboratory for renewable energy and energy efficiency research and development. NREL is operated for DOE by the Alliance for Sustainable Energy LLC.

Their discovery about brain cells called microglia heralds myriad possibilities for treating and even preventing neurodegenerative disorders. The team’s paper appears in the Journal of Experimental Medicine.

When microglia are healthy, they serve as the central nervous system’s resident front-line disease warriors. “However, there is overwhelming evidence that they can become dysfunctional in many neurological conditions,” said Mathew Blurton-Jones, UCI professor of neurobiology & behavior and study co-lead author. “Until recently, scientists have mainly been looking at the mechanisms that drive microglial dysfunction and trying to find drugs to change their activity. But with this study, we’ve found a way to potentially harness microglia themselves to treat those diseases.”

Frederick “Chris” Bennett, assistant professor of psychiatry at Penn and co-lead author, added: “There is an obstacle because once our own microglia develop in the location where they are supposed to be in our brains, they don’t give up that space. They block the ability to deliver new cells that would take their place. If you want to insert donor microglia, you have to deplete the host microglia to open up room.”

Bennett and his laboratory partnered with Blurton-Jones and his lab on the project.

Microglia depend on signaling by a protein on their surface called CSF1R for their survival. The FDA-approved cancer drug pexidartinib has been found to block that signaling, killing them. This process would seem to offer a way to clear space in the brain to insert healthy donor microglia. However, there is a dilemma — unless the pexidartinib is stopped before the donor microglia are added, it will eliminate them, too. But once the drug is terminated, the host microglia regenerate too fast to effectively put in the donor cells.

This quandary has challenged efforts to treat people with certain rare and severe neurologic conditions. One is Krabbe disease, in which the body’s cells can’t digest certain fats that are highly abundant in the brain. Currently, clinicians use bone marrow transplantation and chemotherapy to try to introduce new immune cells similar to microglia into the brain. But this approach can be toxic and must be carried out before Krabbe symptoms manifest.

“Our team believed that if we could overcome the brain’s resistance to accepting new microglia, we could successfully transplant them into patients using a safer, more effective process in order to target a great number of diseases,” said co-first author Sonia Lombroso, a Penn Ph.D. student and member of the Bennett Lab. “We decided to investigate whether we could make the donor microglia resistant to the drug that eliminates their host counterparts.”

The researchers used CRISPR gene-editing technology to create one amino acid mutation, known as G795A, which they introduced into donor microglia produced from human stem cells or a mouse microglial cell line. Then they injected the donor microglia into humanized rodent models while administering pexidartinib, with exciting results.

“We discovered that this one small mutation caused the donor microglia to resist the drug and thrive, while the host microglia continued to die off,” said co-first author Jean Paul Chadarevian, a UCI Ph.D. student who is a member of the Blurton-Jones Lab. “This finding could lead to many options for developing new microglial-based treatments. Pexidartinib is already approved for clinical use and appears to be relatively well tolerated by patients.”

Approaches could range from fighting disease by replacing dysfunctional microglia with healthy ones to designing microglia that can recognize imminent threats and strike against them with therapeutic proteins before they cause harm.

The UCI-Penn team believes treatments based on this kind of microglial method could be developed within a decade. Their next investigations include studying in rodent models how to use the approach to attack the brain plaques associated with Alzheimer’s and to counter Krabbe and other similar diseases.

Support for the project was provided by the National Institutes of Health, National Science Foundation, The Paul Allen Frontiers Group, Klingenstein-Simons Fellowship Award in Neuroscience and the Susan Scott Foundation.