The research, which benefited from a collaboration with experts at the University of Maryland School of Medicine and focused on microglia in the brain and spinal cord, is published today in leading international journal, Science Advances.

Microglia are a unique type of immune cell whose job it is to support nerve cells, defend against invading microbes, clear debris and remove dying nerve cells by engulfing and eating them. Emerging research indicates that microglia can have different functional responses depending on molecular and biochemical changes occurring within these specialised cells.

In fact, various subtypes of microglia can be distinguished based on a property called autofluorescence. This is the tendency of cells to emit light of one colour after they have absorbed light of another, and it occurs because specific substances inside the cells absorb light. The substances stored in specialised cellular compartments include fat molecules, cholesterol crystals, metals and other misfolded proteins.

David Loane, Assistant Professor of Neuroscience in Trinity’s School of Biochemistry and Immunology in TBSI is the lead author of the research. He said:

“As the brain ages, these materials build up inside autofluorescent microglia, which increase their autofluorescence as a result. Unfortunately, this accumulation of cellular debris also makes it harder for the microglia to perform their essential garbage collection tasks in the brain and to prevent neurological injury and neurodegenerative disease.

“In this study we found — in aged animals — that these microglia adopt a unique, dysfunctional state, which has a number of problematic impacts. For example, there is an increase in cellular stress and damage, an accumulation of fats and iron, alterations to metabolic processes and an increase in production of molecules that over-egg the immune response.”

In addition, the scientists demonstrated that autofluorescent microglia and associated inflammation were more pronounced under pathological conditions, such as in genetic risk factor models of Alzheimer’s disease, and — promisingly — were reversed by drug-assisted microglial replacement in aged animals.

Prof Loane added: “Furthermore, environmental exposure to acute traumatic brain injury in animals accelerated the age of onset and tissue-wide distribution autofluorescent microglia by increasing oxidative stress damage in the brain of injured animals.

“As a result, increasing evidence now suggests that the accumulation of autofluorescent microglia contributes to diseases of ageing and neurodegeneration. If these sub-populations of microglia are highly inflammatory and damaging to the brain, then targeting them could be a new strategy for treating aging-related diseases.”

“Finding a nonsurgical treatment for hydrocephalus, given the fact neurosurgery is fraught with tremendous morbidity and complications, has been the holy grail for our field,” says Kristopher Kahle, MD, PhD, a pediatric neurosurgeon at MGH and senior author of the study. “We’ve identified through a genome-wide analytical approach the mechanism that underlies the swelling of the ventricles which occurs after a brain bleed or brain infection in acquired hydrocephalus. We’re hopeful these findings will pave the way for approval of an anti-inflammatory drug to treat hydrocephalus, which could be a game-changer for populations in the U.S. and around the world that don’t have access to surgery.”

Acquired hydrocephalus occurs in about one of every 500 births globally. It is the most common cause of brain surgery in children, though it can affect people at any age. In underdeveloped parts of the world where bacterial infection is the most prevalent form of the disease, hydrocephalus is often deadly for children due to the lack of surgical intervention. Indeed, the only known treatment for acquired hydrocephalus is brain surgery, which involves implantation of a catheter-like shunt to drain fluid from the brain. But about half of all shunts in pediatric patients fail within two years of placement, according to the Hydrocephalus Association, requiring repeat neurosurgical operations and a lifetime of brain surgeries.

By deciphering the unique cellular and molecular biology that occurs within the brain after infection or severe hemorrhage, the MGH-led research team has taken a major step toward nonsurgical, pharmacologic treatment for humans. Pivotal to the process is the choroid plexus, the brain structure that routinely pumps cerebrospinal fluid into the four ventricles of the brain to keep the organ buoyant and injury-free within the skull. An infection or brain bleed, however, can create a dangerous neuroinflammatory response where the choroid plexus floods the ventricles with cerebral spinal fluid and immune cells from the periphery of the brain — a so-called “cytokine storm,” or immune system overreaction, so often seen in COVID-19 infections — swelling the brain ventricles.

“Scientists in the past thought that entirely different mechanisms were involved in hydrocephalus from infection and from hemorrhage in the brain,” explains co-author Bob Carter, MD, PhD, chair of the Department of Neurosurgery at MGH. “Dr. Kahle’s lab found that the same pathway was involved in both types and that it can be targeted with immunomodulators like rapamycin, a drug that’s been approved by the U.S. Food and Drug Administration for transplant patients who need to suppress their immune system to prevent organ rejection.”

MGH researchers are continuing to explore how rapamycin and other repurposed drugs which quell the inflammation seen in acquired hydrocephalus could be turned into an effective drug treatment for patients. “What has me most excited is that this noninvasive therapy could provide a way to help young patients who don’t have access to neurosurgeons or shunts,” emphasizes Kahle. “No longer would a diagnosis of hydrocephalus be fatal for these children.”

Kahle is director of Pediatric Neurosurgery at MGH, and director of the Harvard Center for Hydrocephalus and Neurodevelopmental Disorders. Carter is chief of Neurosurgery Service at MGH and professor of Surgery at Harvard Medical School.

The study was funded by the National Institutes of Health and the Hydrocephalus Association.

In a study published in Physical Review Letters, researchers at Aalto University in Finland and IAS Tsinghua University in China report a new way to predict how quantum systems, such as groups of particles, behave when they are connected to the external environment. Usually, connecting a system such as a quantum computer to its environment creates decoherence and leaks, which ruin any information about what’s happening inside the system. Now, the researchers developed a technique which turns that problem into its a solution.

The research was carried out by Aalto doctoral researcher Guangze Chen under the supervision of Professor Jose Lado and in collaboration with Fei Song from IAS Tsinghua. Their approach combines techniques from two domains, quantum many-body physics and non-Hermitian quantum physics.

Protection from decoherence and leaks

One of the most intriguing and powerful phenomena in quantum systems is many-body quantum correlations. Understanding these and predicting their behaviour is vital because they underpin the exotic properties of key components of quantum computers and quantum sensors. While a lot of progress has been made in predicting quantum correlations when matter is isolated from its environment, doing so when matter is coupled to its environment has so far eluded scientists.

In the new study, the team showed that connecting a quantum device to an external system can be a strength in the right circumstances. When a quantum device is host to so-called non-Hermitian topology, it leads to robustly protected quantum excitations whose resilience stems from the very fact that they are open to the environment. These kinds of open quantum systems can potentially lead to disruptive new strategies for quantum technologies that harness external coupling to protect information from decoherence and leaks.

From idealised conditions to the real world

The study establishes a new theoretical method to calculate the correlations between quantum particles when they are coupled to their environment. ‘The method we developed allows us to solve correlated quantum problems that present dissipation and quantum many-body interactions simultaneously. As a proof of concept, we demonstrated the methodology for systems with 24 interacting qubits featuring topological excitations,’ says Chen.

Professor Lado explains that their approach will help move quantum research from idealised conditions to real-world applications. ‘Predicting the behavior of correlated quantum matter is one of the critical problems for the theoretical design of quantum materials and devices. However, the difficulty of this problem becomes much greater when considering realistic situations in which quantum systems are coupled to an external environment. Our results represent a step forward in solving this problem, providing a methodology for understanding and predicting both quantum materials and devices in realistic conditions in quantum technologies,’ he says.