Tag Archive for: Microglia

illustration of neurons

New AI platform accelerates brain inflammation research 10,000-fold

illustration of neurons

A new AI tool developed by Children’s National and Howard University analyzes brain immune cells 10,000x faster than manual methods.

A new Machine Learning and Artificial Intelligence tool from researchers at Children’s National Hospital (CNH) and Howard University (HU) accelerates discoveries in brain inflammation. Called StainAI, it rapidly and accurately analyzes microglia, the brain’s immune cells. Scientists currently analyze microglia slowly by hand. StainAI automates this process and speeds it up 10,000-fold. Its use will aid discovery of new treatments for inflammatory brain conditions such as infection, autoimmunity, and aging.

Solving a problem

Traditionally, scientists study microglia one cell at a time. They reconstruct each cell’s shape by hand under a microscope. The shape helps classify microglia as “resting” (normal) or “activated” (inflamed). The manual process is tedious and slow. It limits analyses to a few microglia in small brain areas.

StainAI changes that. It uses deep machine learning and artificial intelligence to overcome and exceed the manual method’s limitations. It correctly classifies millions of microglia from standard microscopic images. StainAI also localizes each microglia to its brain region in 3D. These features enable single-cell analyses of immune activity at a scale not feasible before – the entire brain.

A tool with broad impact

The team applied StainAI to two models of brain injury and inflammation to show its utility. In a rodent model of pediatric cardiac arrest, StainAI identified new brain regions susceptible to injury. In a simian model of viral infection, StainAI localized rod-shaped microglia normally found in white matter to an unexpected brain region – the hippocampus.  These findings point towards new treatments and highlight StainAI’s value across diseases and species.

StainAI is fast, accurate and adaptable. It uses common laboratory equipment. Its creators, Michael Shoykhet, MD, PhD, at CNH and Dr. Tsang-Wei Tu at HU, are making StainAI available to other researchers. They hope StainAI will help labs worldwide discover new ways to protect children’s brains from inflammation and injury.

You can read the full article, StainAI: quantitative mapping of stained microglia and insights into brain-wide neuroinflammation and therapeutic effects in cardiac arrest, in Communications Biology, a Nature group journal.

glial cells

Dr. Nathan A. Smith receives $600,000 DOD ARO grant to study the role of glial cells in neural excitability and cognition

glial cells

Microglia are the resident immune cells of the central nervous system that have highly dynamic processes that continuously survey the brain’s microenvironment, making contact with both neurons and astrocytes.

In his pursuit to understand the function of neural circuits within the brain, Nathan A. Smith, M.S., Ph.D., principal investigator at Children’s National Hospital, is examining how specialized glial cells, known as astrocytes and microglia, work together to influence neural networks and potentially enhance neuro-cognition.

Dr. Smith has just secured a new $600,000 grant from the Department of Defense Army Research Laboratory to pursue cutting-edge experimental approaches to examine the role of astrocytes in Ca2+-dependent microglia modulation of synaptic activity. This project will enhance our understanding of neuronal excitability and cognition, and define a new role for microglia in these processes.

“Glia cells play an important role in modulating synaptic function via Ca2+-dependent mechanisms,” says Dr. Smith. “It’s time for these cells to receive recognition as active participants, rather than passive contributors, in fundamental neural processes.”

Dr. Smith and his laboratory at Children’s National Research Institute are using novel experimental models to study the dynamics underlying Ca2+-mediated microglia process extension and retraction to further our understanding of how microglia, astrocytes and neurons interact in the healthy brain.

“Completion of the proposed studies has the potential to redefine the role(s) of microglia in higher brain functions and highlight the significant contribution of these cells,” Dr. Smith says. “Most importantly, elucidating the mechanisms that underlie glial cell modulation of neural circuits will not only further our understanding of normal brain function but also open new avenues to developing more accurate computational models of neural circuits.”

Dr. Nathan Smith

Dr. Smith and his laboratory at Children’s National Research Institute are using novel experimental models to study the dynamics underlying Ca2+-mediated microglia process extension and retraction to further our understanding of how microglia, astrocytes and neurons interact in the healthy brain.

Microglia are the resident immune cells of the central nervous system that have highly dynamic processes that continuously survey the brain’s microenvironment, making contact with both neurons and astrocytes. However, because of our inability to directly monitor Ca2+ activity in microglia, very little is known about the intracellular Ca2+ dynamics in resting microglia and their role in surveillance and modulation of synaptic activity.

Dr. Smith’s research team and his use of cutting-edge technology are a perfect match with the Army’s new modernization priorities. Dr. Smith’s research program and the new Army’s initiatives will greatly benefit from each other and ultimately contribute to a better understanding of the human brain.

“This research will help address a major gap in our understanding of the roles that glial cells play in regulating the computations of the nervous system through their interactions with neurons, which could also inspire a new class of artificial neural network architectures,” said Dr. Frederick Gregory, program manager, Army Research Office, an element of the U.S. Army Combat Capabilities Development Command’s Army Research Laboratory.

The grant will begin on July 1, 2020, and will last over three years. Dr. Smith’s research is also supported by other grants, including awards from the NIH and the National Science Foundation.

“As Dr. Smith’s mentor, the ultimate joy for a mentor is to see his mentees follow their dreams and be recognized for their accomplishments,” said Vittorio Gallo, Ph.D., Chief Research Officer at Children’s National Hospital. “I couldn’t be prouder of Nathan, and I am fully confident that this new research grant will help him continue to grow an exceptional research program.”