Leukomalacia, Periventricular

In experiments using neonatal mice, researchers have identified a fatty molecule in breast milk that triggers a process in which stem cells in the brain produce cells that create new white matter, reversing brain injury. While it's known that the white matter loss will lead to neurological deficits, there is currently no treatment to help these infants avoid the outcome. In experiments using neonatal mice, researchers at Duke Health have identified a fatty molecule in breast milk that triggers a process in which stem cells in the brain produce cells that create new white matter, reversing the injury. The study appears Aug. 3 in the journal Cell Stem Cell. Eric Benner, M.D., Ph.D., is the study's corresponding author and is a distinguished assistant professor in the Department of Pediatrics at Duke University School of Medicine. Benner said further study in a clinical trial is needed, but the finding is promising. "Developing therapies for children -- especially such medically fragile children -- is very difficult to do because there are justifiably strict safety concerns," Benner said. "The fact that this molecule is already found in something that is safe for premature babies -- breast milk -- is extremely encouraging. "It's been known that fats in breast milk benefit a child's brain development, but there are many types of fats in breast milk," Benner said. "This work has identified a lipid molecule in breast milk that promotes white matter development. Now, we can begin to develop a therapy that isolates and delivers this lipid in a way that is safe for the unique challenges of these infants." Benner is a neonatologist at Duke University and one of the co-founders of Tellus Therapeutics, a Duke spinout company developed with the help of the Duke University Office for Translation & Commercialization to bring this therapy from the bench into the neonatal intensive care unit. The fatty molecule identified in the study will be administered intravenously to patients in an upcoming clinical trial. This is significant because many of the infants who are part of this vulnerable population also have gastrointestinal issues and cannot safely be given milk or medication by mouth. The lipid molecule enters the brain and binds with stem cells there, encouraging the stem cells to become or produce a type of cell called oligodendrocytes. The oligodendrocytes are like a hub that allow for the production of white matter in the central nervous system. This newly produced white matter in pre-term infants prevents the neurological damage that would otherwise impact the child's ability to move -- the hallmarks of cerebral palsy. "The timing of brain injury is extremely difficult to predict, thus a treatment that could be safely given to all preterm babies at risk would be revolutionary," said Agnes Chao, M.D., a former fellow in the Division of Neonatology and first author of the paper. "As a neonatologist, I'm so excited that I may be able to offer a treatment to families with babies that are affected by preterm brain injury who would otherwise have no other options," Chao said. In addition to Benner and Chao, study authors include Pavle Matak, Kelly Pegram, James Powers, Collin Hutson, Rebecca Jo, Laura Dubois, J. Will Thompson, P. Brian Smith, Jason R. Gibson, Noelle E. Younge, Blaire Rikard, Simon G. Gregory, Ronald N. Goldberg, Mari L Shinohara, Estefany Y. Reyes, Chunlei Liu. The study was funded by the National Institutes of Health (1R01NS114578, T32HD094671, K12HD043494, T32HD043728, R01AG070826, R01MH127104, P41EB015897, 1UL1-TR002553), Jean and George Brumley Jr. Neonatal Perinatal Research Institute, with additional support from the Duke Scholars Award from the School of Medicine, Duke University Center for In Vivo Microscopy, and the National Center for Advancing Translational Sciences.

The company designed its next-generation TAVR system to treat aortic stenosis. With a unique concave and convex structure, the TAVR system anchors the valve effectively in the aortic annulus. This helps to avoid common complications with TAVR, including implant dislodging or perivalvular leak (PVL) due to improper fit, according to the company. The valve also features differential radial force in different parts, according to a news release. It imparts low or high radial forces to the valve depending on the location within the annulus and aorta. Onecrea said it designed the delivery system with improvements for greater control and accuracy for implantation. About the first-in-human implants for Onecrea Medical Dr. Carlos Calderas supervised a team of surgeons that performed the implantations for the first-in-human effort for the Onecrea valve. The first patient, an 82-year-old woman, had a history of severe shortness of breath and severe symptomatic aortic stenosis. She underwent a giant abdominal aortic aneurysm (AAA) repair recently. Calderas successfully implanted a 26 mm Crea aortic valve through the femoral approach. The patient was discharged from the hospital after three days with a mean gradient of 8 mmHg and no PVL. Onecrea said that the second patient, an 88-year-old-woman, was referred to consider TAVR because of severe symptomatic aortic stenosis. She recently went to the emergency room for heart failure requiring mechanical ventilation. This led to a diagnosis of severe aortic stenosis and shortness of breath. The team implanted a 26 mm Crea valve through the femoral approach with the 18F introducer. At discharge five days later, the patient recorded a mean gradient of 7 mmHg and no PVL. “The design of the Crea Aortic Valve is truly exceptional, revolutionizing the way we approach TAVR procedures,” Calderas said. “The delivery system was remarkably easy to use, increasing the accuracy of valve placement. This means less time operating on the patient while decreasing the risk of paravalvular leaking and implant dislodging. The valve’s innovative engineering ensures optimal hemodynamics and durability, providing patients with a reliable and long-lasting solution.” Onecrea continues to enroll patients in a larger clinical study conducted across multiple centers.

THURSDAY, May 11, 2023 -- Poor sleep brought on by sleep apnea may ultimately undermine the brain health of older men and women, new research suggests. The concern stems from a new brain scan investigation that involved 140 sleep apnea patients. “Sleep apnea is a medical condition in which patients ... stop breathing during sleep, which can affect their sleep quality by causing multiple arousals and dropping oxygen levels,” said lead study author Dr. Diego Carvalho . He is an assistant professor of neurology at the Mayo Clinic Center for Sleep Medicine in Rochester, Minn. Sleep apnea “has been associated with increased risk of high blood pressure, diabetes, heart attack, stroke, cognitive impairment and dementia,” Carvalho said. And, he noted, it is known to “cause a range of harmful effects in the brain,” as blood pressure and heart rate rise, oxygen levels drop and sleep is disrupted. Importantly, sleep apnea can limit a person’s ability to get and maintain “deep sleep.” Deep sleep, which begins about an hour after falling asleep, is essential to the body’s ability to repair and regenerate tissue, bolster the immune system, and build bone and muscle, according to the Cleveland Clinic. Getting enough of it is, therefore, considered a key indicator of good quality shut-eye. With that in mind, Carvalho and his team set out to see whether the impact of sleep apnea on deep sleep might somehow be linked to the long-term risk for stroke, dementia and Alzheimer’s disease. The study included 140 participants (average age, 73 years). None had any signs of dementia, Alzheimer’s or trouble with thought processing when the study was conducted. Their sleep apnea ranged in severity from mild to severe. Each participant underwent brain scans and an overnight study in a sleep lab. The scans offered insight into the health of nerve fibers that make up the brain's white matter. White matter damage can undermine communication between different parts of the brain. It often shows up as tiny lesions that accumulate with age. The overnight study allowed researchers to track sleep patterns. The result: After comparing sleep to scans, the researchers found that patients who got the least deep sleep — and, therefore, had the poorest overall sleep quality — were also the most likely to show telltale signs of white matter damage. For every 10-point drop in the percentage of deep sleep, the investigators found an increase in white matter damage similar to the effect of aging an additional 2.3 years. “Poor sleep from severe sleep apnea or decreased deep sleep may be involved in white matter abnormalities thought to contribute to the risk of cognitive impairment, dementia and stroke,” Carvalho said. But the study authors also pointed out some key caveats. For one thing, the association between less deep sleep and more white matter damage “was just evident in patients with severe sleep apnea,” not among those with less advanced disease. And investigators placed a heavy emphasis on “association.” The findings, they said, only highlight a link between poor sleep quality and higher risk for mental decline and stroke down the road. They don't yet prove that one actually causes the other. “That being the case, future studies should assess whether strategies to improve sleep quality and enhance this stage of sleep could help prevent development of progression of white matter abnormalities,” Carvalho added. Dr. Ivana Rosenzweig , head of the Sleep and Brain Plasticity Center at King's College London in the United Kingdom, reviewed the new study findings. She stressed that “sleep apnea is a serious public health problem that affects most of our body organs and our brain,” with the number of affected patients predicted to rise in coming years. “Whilst the jury is still out regarding how the deep sleep may exactly affect memory, a number of studies show strong links between normal aging, less time spent in deep sleep and memory issues,” Rosenzweig said. She added that the new findings “appear to support a growing body of literature which suggests that sleep apnea may in some susceptible individuals lead to accelerated aging processes in the body and the brain.” Rosenzweig’s take: “Studies such as this are important, as they help to raise awareness of the importance of sleep quality in our battle against dementia,” while also indicating “how important certain sleep building blocks and rhythms may be for the health of our brain.” The findings were published online May 10 in the journal Neurology . Sources Diego Carvalho, MD, MS, assistant professor, neurology, Center for Sleep Medicine, Mayo Clinic, Rochester, Minn. Ivana Rosenzweig, MD, PhD, head, Sleep and Brain Plasticity Center, Institute of Psychiatry, Psychology and Neuroscience, King's College London, U.K. Neurology , May 10, 2023, online Posted May 2023