UC Irvine-led study discovers novel cause of brain hemorrhage

In vivo microhemorrhages linked to erythrocyte-brain endothelial interactions

By Dr. Prajakta Banik, Tech Explorist

A groundbreaking study led by the University of California, Irvine, has uncovered a surprising cause of brain hemorrhages that doesn’t involve damage to blood vessels, challenging previous beliefs. The research found that interactions between aged red blood cells and brain capillaries can lead to cerebral microbleeds, shedding light on their formation and suggesting new avenues for treatment and prevention.

Published in the Journal of Neuroinflammation, the study observed red blood cells stalling in brain capillaries and the subsequent occurrence of hemorrhages. These microbleeds are linked to conditions more common in older adults, such as hypertension, Alzheimer’s disease, and ischemic stroke.

Co-corresponding author Dr. Mark Fisher, professor of neurology at UCI’s School of Medicine, said, “We have previously explored this issue in cell culture systems, but our current study is significant in expanding our understanding of the mechanism by which cerebral microbleeds develop. Our findings may have profound clinical implications, as we identified a link between red blood cell damage and cerebral hemorrhages at the capillary level.”

The research team treated red blood cells with a chemical, tert-butyl hydroperoxide, inducing oxidative stress. After marking the cells with fluorescence, they injected them into mice. The researchers witnessed the red blood cells getting stuck in brain capillaries through two observation methods. Subsequently, a process called endothelial erythrophagocytosis cleared the cells out. As the cells moved out, microglia inflammatory cells engulfed them, triggering the formation of a brain hemorrhage.

Co-corresponding author Xiangmin Xu, UCI professor of anatomy & and neurobiology and director of the campus’s Center for Neural Circuit Mapping, said, “It has always been assumed that for cerebral hemorrhage to occur, blood vessels need to be injured or disrupted. We found that increased red blood cell interactions with the brain capillaries represent an alternative source of development. We need to examine in detail the regulation of brain capillary clearance and also analyze how that process may be related to insufficient blood supply and ischemic stroke, which is the most common form of stroke, to help advance the development of targeted treatments.”

The UC Irvine-led study is pioneering in revealing a non-vascular cause for brain hemorrhages, significantly advancing our understanding of this complex medical phenomenon. This newfound knowledge holds promise for developing innovative therapeutic interventions and preventive measures, marking a crucial step forward in neurology.

Journal reference:

Zhang, H., Sumbria, R.K., Chang, R. et al. Erythrocyte–brain endothelial interactions induce microglial responses and cerebral microhemorrhages in vivo. Journal of Neuroinflammation. DOI: 10.1186/s12974-023-02932-5

Click here to read full Tech Explorist article.

UC Irvine-led study is first to find brain hemorrhage cause other than injured blood vessels

Discovery deepens understanding of cerebral microbleeds, may offer new therapeutic targets

Irvine, Calif., Nov. 20, 2023 — A first-of-its-kind study led by the University of California, Irvine has revealed a new culprit in the formation of brain hemorrhages that does not involve injury to the blood vessels, as previously believed. Researchers discovered that interactions between aged red blood cells and brain capillaries can lead to cerebral microbleeds, offering deeper insights into how they occur and identifying potential new therapeutic targets for treatment and prevention.

The findings, published online recently in the Journal of Neuroinflammation, describe how the team was able to watch the process by which red blood cells stall in the brain capillaries and then observe how the hemorrhage happens. Cerebral microbleeds are associated with a variety of conditions that occur at higher rates in older adults, including hypertension, Alzheimer’s disease and ischemic stroke.

“We have previously explored this issue in cell culture systems, but our current study is significant in expanding our understanding of the mechanism by which cerebral microbleeds develop,” said co-corresponding author Dr. Mark Fisher, professor of neurology in UCI’s School of Medicine. “Our findings may have profound clinical implications, as we identified a link between red blood cell damage and cerebral hemorrhages that occurs at the capillary level.”

The team exposed red blood cells to a chemical called tert-butyl hydroperoxide that caused oxidative stress; the cells were then marked with a fluorescent label and injected into mice. Using two different methods, the researchers observed the red blood cells getting stuck in the brain capillaries and then being cleared out in a process called endothelial erythrophagocytosis. As they moved out of the capillaries, microglia inflammatory cells engulfed the red blood cells, which led to the formation of a brain hemorrhage.

“It has always been assumed that in order for cerebral hemorrhage to occur, blood vessels need to be injured or disrupted. We found that increased red blood cell interactions with the brain capillaries represent an alternative source of development,” said co-corresponding author Xiangmin Xu, UCI professor of anatomy & neurobiology and director of the campus’s Center for Neural Circuit Mapping. “We need to examine in detail the regulation of brain capillary clearance and also analyze how that process may be related to insufficient blood supply and ischemic stroke, which is the most common form of stroke, to help advance the development of targeted treatments.”

Leveraging the broad, collaborative infrastructure and robust resources of the Center for Neural Circuit Mapping, other team members were Rachita Sumbria, co-first author/co-corresponding author and associate professor in the Chapman University School of Pharmacy; Hai Zhang, co-first author and postdoctoral researcher in UCI’s Department of Anatomy & Neurobiology; Rudy Chang, co-first author and Chapman University School of Pharmacy graduate student; Jiahong Sun, postdoctoral researcher at Chapman University; David Cribbs, professor-in-residence at UCI’s Institute for Memory Impairments and Neurological Disorders; and Todd Holmes, UCI professor of physiology & biophysics.

This work was supported by the National Institute on Aging under award numbers R01AG062840, R01AG072896, R35127102, RF1 AG065675 and R01NS121246 and by National Institute of Neurological Disorders and Stroke grant R01NS20989.

Click here to read full UCI News press release.

A New Understanding of Brain Hemorrhages: Exploring the Role of Red Blood Cell Interactions

By , Express Healthcare Management

A groundbreaking study conducted by the University of California, Irvine has unveiled a previously unknown contributor to the formation of brain hemorrhages that does not involve blood vessel injury. The research team discovered that interactions between aged red blood cells (RBCs) and brain capillaries can lead to cerebral microbleeds, shedding light on the underlying mechanisms and potential therapeutic targets for treatment and prevention.

Published in the Journal of Neuroinflammation, the study utilized advanced imaging techniques to observe the process by which RBCs become stalled in brain capillaries and subsequently trigger hemorrhages. Cerebral microbleeds are often associated with conditions that occur more frequently in older adults, such as hypertension, Alzheimer’s disease, and ischemic stroke.

Co-corresponding author Dr. Mark Fisher, a professor of neurology at UCI’s School of Medicine, emphasized the significance of this study in expanding our understanding of how cerebral microbleeds develop. He stated, “Our findings may have profound clinical implications, as we identified a link between red blood cell damage and cerebral hemorrhages that occurs at the capillary level.”

To investigate this link, the research team exposed RBCs to tert-butyl hydroperoxide, a chemical that induces oxidative stress. The treated RBCs, labeled with a fluorescent marker, were then injected into mice. Through two different imaging methods, the researchers observed the RBCs becoming lodged in brain capillaries and subsequently cleared out via endothelial erythrophagocytosis. As the RBCs were cleared, microglia inflammatory cells engulfed them, leading to the formation of brain hemorrhages.

Co-corresponding author Xiangmin Xu, a UCI professor of anatomy and neurobiology, highlighted the implications of their discoveries, stating, “We need to examine in detail the regulation of brain capillary clearance and analyze how this process relates to insufficient blood supply and ischemic stroke to advance the development of targeted treatments.”

This study marks a significant step forward in uncovering the contributors to brain hemorrhages and offers potential avenues for the development of new therapies. By focusing on the interactions between RBCs and brain capillaries, researchers can further explore the regulation of capillary clearance and its connections to other conditions such as ischemic stroke.

FAQ

What are cerebral microbleeds?
Cerebral microbleeds refer to small bleeding spots in the brain, often associated with conditions like hypertension, Alzheimer’s disease, and ischemic stroke. These microbleeds occur at a capillary level and were previously believed to be caused solely by blood vessel injury.

What did the study uncover?
The study discovered that interactions between aged red blood cells and brain capillaries can lead to cerebral microbleeds. By exposing red blood cells to oxidative stress and observing their behavior in mouse models, the researchers observed how the red blood cells become stuck in the capillaries and trigger the formation of brain hemorrhages.

What are the implications of these findings?
The findings of this study have significant clinical implications as they provide a new understanding of the development of cerebral microbleeds. Identifying the link between red blood cell damage and brain hemorrhages at the capillary level opens up potential avenues for targeted treatments and prevention strategies.

What further research is needed in this area?
Further research is needed to delve into the regulation of brain capillary clearance and to analyze its connection to insufficient blood supply and ischemic stroke. Understanding these processes can contribute to the development of more effective treatments for conditions associated with cerebral microbleeds.

Click here to read full Express Healthcare Management article.

A new cause of brain hemorrhage has been identified

Photo: Depositphotos

Bronwyn Thompson, New Atlas

In a significant development for brain health, scientists have demonstrated for the first time how hemorrhages can occur due to a faulty interaction between aged red blood cells and narrow capillaries. Until now, the cause of this serious condition has been brain bleeding that results from injured or damaged blood vessels.

“It has always been assumed that in order for cerebral hemorrhage to occur, blood vessels need to be injured or disrupted,” said co-corresponding author Xiangmin Xu, professor at University of California Irvine (UCI). “We found that increased red blood cell interactions with the brain capillaries represent an alternative source of development.”

The team identified how aged red blood cells ‘stall’ in the brain’s narrow network of capillaries, which result in microbleeds at the site. Cerebral microbleeds in older adults have been linked to a higher risk of developing Alzheimer’s disease, hypertension and ischemic stroke.

While capillaries – the smallest blood vessels in the body – employ a clever membranous mechanism to push out any blockages, it’s a system that begins to falter with age.

The 2010 study that identified this mechanism also found that it becomes 30 to 50% slower in an aging brain, and also results in the death of more capillaries.

The team used tert-butyl hydroperoxide to cause oxidative stress to red blood cells, then marked the cells with a fluorescent tag and injected them into the brains of mice. Through two different methods, they saw the red blood cells becoming stuck in the capillaries, before being cleared through the process known as endothelial erythrophagocytosis. But as the cells moved out, microglia inflammatory cells engulfed them, forming a brain hemorrhage.

“We have previously explored this issue in cell culture systems, but our current study is significant in expanding our understanding of the mechanism by which cerebral microbleeds develop,” said co-corresponding author Mark Fisher, professor at UCI’s School of Medicine. “Our findings may have profound clinical implications, as we identified a link between red blood cell damage and cerebral hemorrhages that occurs at the capillary level.”

The team says this finding presents new avenues of research and potential treatment to help an aging brain maintain capillary function and to prevent those aged cells from stalling along this essential transport route.

“We need to examine in detail the regulation of brain capillary clearance and also analyze how that process may be related to insufficient blood supply and ischemic stroke, which is the most common form of stroke, to help advance the development of targeted treatments,” Fisher added.

The study was published in the Journal of Neuroinflammation.

Source: University of California Irvine

Click here to read full New Atlas article.

UCI Samueli School of Engineering 2022-23 Dean’s Report

The e+ Equation

Inside
In this issue of the UCI Samueli School of Engineering 2022-23 Dean’s Report, you will learn how collaboration inspires the school’s EngineeringPlus approach to its mission of education, research and partnerships. The inclusive concept involves looking beyond one’s own expertise to engineer innovative solutions for the grand challenges facing society. Please enjoy reading about UCI engineering researchers, students and alumni who use their expertise, imagination and creativity to enhance the human experience.

Faculty Accolades
Early Career – MAXIM SHCHERBAKOV, DARPA Young Faculty

MOMS
Biomedical engineers MICHELLE KHINE and BERNARD CHOI have combined their technologies to create the Maternal Obstetrics Monitoring Sock, a low-cost, point-of-care system to monitor pregnant women for preeclampsia, anemia and hemorrhage. According to the NIH, pregnancy and childbirth complications are a major global health problem and result in the deaths of more than 800 women and 7,000 newborns each day. The smart sock works by integrating the soft beat-to-beat blood pressure sensor that Khine has been developing in her lab with the photonic anemia and hemorrhage sensor from Choi’s lab. The health data is wirelessly transmitted to a smartphone and can alert patients if necessary. The technology is not significantly affected by skin pigmentation or motion artifacts and can be manufactured for under $100.

About the Dean’s Report
The UCI Samueli School of Engineering Dean’s Report is an annual magazine that highlights exciting research, news and faculty accomplishments from the prior year. Issued in the fall, it also conveys a new theme each year to coincide with the school’s progress and the Dean’s priorities.

Click here to read the full UCI Samueli School of Engineering 2022-23 Dean’s Report.

Ig Nobel Prize: Honoring the most ludicrous research studies of the year

By Chrissy Sexton
Earth.com staff writer

It’s that time of the year again, when scientists gather to celebrate the unusual, quirky, and downright weird. This year’s 33rd Ig Nobel Prize ceremony, held virtually on September 14, did not disappoint.

Nostril hair earns an Ig Nobel

Other notable mentions include a team from the University of California, Irvine, who ventured into the unknown territory of counting human nostril hairs.

The goal was to determine whether there are an equal number of hairs in each nostril. “The information we needed was not available in anatomy texts, so we decided to find out on our own,” said team lead Natasha Mesinkovska.

The findings have significant implications for alopecia patients, who often lose nasal hair, which defends against allergens and infections.

Click here to read full article on Earth.com.

Ig Nobel Prizes honor zombie spiders, rock-licking scientists, and a clever commode

After 33 years, the award continues to celebrate brilliant but unusual scientific research

BY PHIE JACOBS

Why do scientists lick rocks? The answer is disappointingly sensible, says Jan Zalasiewicz, a geologist at the University of Leicester. Mineral particles within rocks stand out better on a wet surface than on a dry one, so licking makes rocks easier to identify in the field. And Zalasiewicz waxes nostalgic for the days when scientists did more than just lick rocks—they cooked and, in some cases, actually ate the materials they studied, he noted in a 2017 essay written for the Paleontological Association’s newsletter. “We’ve lost the art of recognizing rocks by taste,” he laments.

For the creative rock-finding techniques described in the essay—part of a series that focuses on what he calls the “quirkier aspects of the rock and fossil world”—Zalasiewicz was one of several scientists honored during this year’s Ig Nobel Prize ceremony, which celebrates comical and eccentric achievements in scientific research.

Zalasiewicz’s reaction to the award? “Bemused,” he says: “It’s nice that the Ig Nobel Committee liked the story.”

The annual Ig Nobel ceremony—cheekily always dubbed the “first annual” despite now being in its 33rd year—draws attention to legitimate scientific pursuits that have some unexpected or humorous aspect. The judges award 10 prizes in a variety of categories, from the traditional Nobel Prize categories of physics, chemistry, physiology or medicine, literature, and peace to additional ones such as public health.

This year, the public health prize went to Stanford University urologist Seung-min Park for his invention of what he calls the Stanford toilet: a “smart” latrine that can monitor an individual’s health by analyzing their urine and feces. Just as people can dive deep into the food and nutrients that go into their bodies, the device allows curious folks to use the latest technologies to analyze their output with granularity: a dipstick test strip checks urine for signs of infections, diabetes, and other illnesses; a computer vision system calculates the speed and amount of urine released; and a sensor identifies each user based on the unique features of their anus. (The “analprint” augments a fingerprint provided before each use of the toilet.)

The literature prize was awarded to researchers who study a phenomenon known as jamais vu, in which an individual perceives something familiar as being unfamiliar—the opposite of déjà vu. Team member Akira O’Connor, a neuroscientist at the University of St. Andrews, explains that it’s possible to re-create this sensation in a laboratory by having subjects repeat a single word many, many, many, many, many times, until the word starts to sound unrecognizable.

O’Connor and his colleagues were initially wary of receiving an Ig Nobel for their work, which they knew ran the risk of making it appear “quirky and frivolous” and therefore easily dismissed, he explains. But O’Connor is nonetheless pleased, hoping the prize will invite more attention to the study of jamais vu and related phenomena.

All the scientists honored during this year’s ceremony—which features laureates of the non-Ig Nobels handing out the awards—have made contributions to their respective fields, even if that research began with Ig Nobel–worthy pursuits. For instance, the team of researchers who won this year’s Ig Nobel for medicine peered into the noses of human cadavers to determine whether there are an equal number of hairs in each nostril. “The information we needed was not available in anatomy texts, so we decided to find out on our own,” says team lead Natasha Mesinkovska, a dermatologist at the University of California, Irvine.

The hairy study could help guide treatment for patients with alopecia, a disease that causes hair loss. People with alopecia often lose their nasal hairs, Mesinkovska explains, leaving them vulnerable to allergies and infection. “Our intention to describe human nose hair growth patterns may seem unusual,” she says, “but it originated from a need to better understand the role they play as front-line guardians of the respiratory system.”

Other winning research included a study that explored reanimating dead spiders in order to use them as mechanical gripping tools. It’s a contribution to the burgeoning (and terrifying) field of “necrobotics,” which uses living (or, more accurately, formerly living) materials to build robots. Another team was honored for aiming to understand how the human brain learns to identify the different sounds that make up words—by investigating the mental activities of people who speak backward.

All winners received a fake $10 trillion Zimbabwean bill, and were emailed a six-page PDF diagram, which could be printed out and folded into a 3D trophy. Marc Abrahams, editor of the scientific humor magazine Annals of Improbable Research and founder of the awards, closed the virtual ceremony with his now-traditional line: “If you didn’t win an Ig Nobel Prize tonight—and especially if you did—better luck next year.”

Click here to visit Science.org.

Meet the winners of the 2023 Ig Nobel Prizes

The award ceremony features miniature operas, scientific demos, and the 24/7 lectures.

Click here to read the full article on the ArsTechnica website.

Durkin Lab receives third place in Military Health System Research Symposium poster awards

The Durkin Lab at UCI Beckman Laser Institute & Medical Clinic, including Drs. Gordon Kennedy, Robert Wilson, Chris Campbell and Anthony Durkin, was awarded third place during the first poster session at the 2023 Military Health System Research Symposium (MHSRS) in Kissimmee, Florida.  The Durkin Lab was recognized with collaborators from the Air Force Research Lab and the US Army Institute for Surgical Research at Joint Base San Antonio (JBSA) Fort Sam Houston, San Antonio, TX.

The work presented was a cross-disciplinary and multi-location collaboration, featuring the use of Institute Spatial Frequency Domain Imaging and Machine Learning technologies to classify burn wound severity, including depth and extent of injury to skin and blood supply. The work is highly relevant to the ability of medical teams to design precision treatment plans for burn wounds in both military and civilian injury scenarios.

The poster presentation was one of more than 1,200 on display at the annual MHSRS. A total of 16 poster awards were given during the meeting.

The research team included: Gordon T. Kennedy1, Robert H. Wilson1,2, William Voorhees3, Christine Kowalczewski5, Jason Payne3, Andrew Kowalczewski6, Chris Campbell1, Jeffrey Whitmore3, Randolph Stone II5, Robert Christy7, James E. Parker4, Anthony J. Durkin1,8

1Beckman Laser Institute and Medical Clinic, University of California Irvine, Irvine, CA; 2Department of Medicine, University of California Irvine, Orange, CA; 3Air Force Research Lab, 711th Human Performance Wing, Airman Systems Directorate, Bioeffects Division, JBSA Ft Sam Houston, San Antonio, TX; 4General Dynamics Information Technology, JBSA Fort Sam Houston, San Antonio, TX; 5U.S. Army Institute of Surgical Research, JBSA Fort Sam Houston, San Antonio, TX; 6Department of Bioengineering & Biomedical Engineering, Syracuse University, Syracuse, NY; 7Military Health Institute, UT Health San Antonio, San Antonio, TX; 8Department of Biomedical Engineering, University of California Irvine, Irvine, CA

Click here to visit the Military Health System Research Symposium website.

Interview with Natasha Atanaskova Mesinkovska, MD, PhD

Featuring Natasha Mesinkovska, MD, PhD |Vice Chair, Clinical Research
University of California Irvine
Irvine, CA | Published September 12, 2023

Interview with Natasha Mesinkovska, MD, PhD

In this installment of Under Your Skin, Dr. Nick Brownstone chats with Dr. Mesinkovska about her favorite disease to treat and which innovations in dermatology she’s most excited about. He also gets a helpful tip on one way to increase efficiency in the office.

What is your favorite disease to treat and why?

Dr. Mesinkovska replies that her favorite disease to treat is alopecia areata because dermatologists finally have a treatment for it. With JAK inhibitors revolutionizing the field, she finds it very satisfying to be able to assure her patients that there is now a treatment available.

She also notes the positive effects of dupilumab for children with atopic dermatitis.

She comments that with the development of baricitinib, the field of alopecia areata has experienced a game-changing event. She also reflects on the positive developments for other types of alopecia that have benefitted from the development of oral minoxidil. She remarks that she’s hopeful more JAK inhibitors will enter the market.

What innovations in dermatology are you most excited about?

Dr. Mesinkovska remarks that she’s happy treatment for chronic inflammatory diseases has shifted from injectables to oral treatments taken daily and that dermatologists are able to treat people more effectively with fewer injections.

In the realm of aesthetic devices, she is also pleased about the development of micro-coring technology, which uses needles big enough to puncture skin and remove tissue but heal without a scar. She remarks that this technology can likely help tighten not only faces, but bodies as well.

In the past 5 years, what is 1 thing you’ve done to increase your efficiency in the office?

Dr. Mesinkovska explains that she realizes what she likes to do and how many people she wants to see, and she accomplishes this by recognizing her own worth. She comments on the urge doctors often have to be people-pleasers but recognizes that she can raise her own value by raising her prices and choosing to see 1 patient instead of 3. This allows her to dedicate more time to that patient and leave the exam room feeling less burnt out while not sacrificing any value monetarily.

Click here to view interview on dermsquared.