Strokes in babies are surprisingly common; here's how the body rushes to
the rescue

Date:
August 31, 2020
Source:
University of Virginia Health System
Summary:
New research is shedding light on the development of the brain's
immune defenses - and how those defenses respond to strokes that
strike one in 4,000 babies in the first month of life.



FULL STORY ==========================================================================
New research from the University of Virginia School of Medicine is
shedding light on the development of the brain's immune defenses -- and
how those defenses respond to strokes that strike one in 4,000 babies
in the first month of life.


==========================================================================
The brain's frontline defenders are immune cells known as microglia. These cells make up 10%-15% of all cells found in the brain. But their
origins have been hotly debated. UVA's Chia-Yi "Alex" Kuan, MD, PhD,
has discovered that many were previously white blood cells known as
monocytes. During brain development -- and in response to infant strokes
-- the monocytes undergo an amazing conversion into troops to defend
the brain.

"Most people believe that blood monocytes only come into the brain
after injury to provoke damage, and then they either die or leave the
brain. Some even say monocytes and microglia live in parallel universes,"
said Kuan, of UVA's Department of Neuroscience and its Center for Brain Immunology and Glia (BIG).

"But our results showed that many microglial cells actually come from
the blood monocytes, both in normal development and after newborn brain injury." The Brain's Immune Defenders The finding is the latest from
UVA's Department of Neuroscience and BIG center, which have in recent
years revolutionized our understanding of the brain's relationship with
the immune system. To explore the origins of the brain's immune defenses,
Kuan and his colleagues developed an innovative new lab model that should greatly benefit future research. That model allowed his team to trace
the origins of microglia in the brains of lab mice.

The researchers found that many monocytes transform into microglia over
the course of brain development. This was a surprise -- prior to UVA's discovery, scientists widely believed that microglia do not come from
the blood monocytes.

But Kuan's team used a process called "fate mapping" to reveal the
microglia's secret origins.

In addition, Kuan's team found that monocytes rush to the rescue during neonatal stroke. Neonatal strokes are interruptions of blood flow to the
baby's brain in the first 28 days after birth. Such strokes have a wide
variety of causes, from blood clots to developmental abnormalities. Common symptoms include seizures and extreme sleepiness, though in some cases
there are no symptoms until much later in life, when children can develop speech difficulties and balance problems.

In such strokes, Kuan found, there is an initial rush of monocytes,
which then gradually become more like microglia. This lasts at least
62 days after the brain injury. Some of these monocytes are ultimately reprogrammed to join the brain's defense forces, the UVA researchers determined.

"But do monocyte-descended microglia continue to impair brain development
in infants that suffered from newborn stroke, leading to neurological
deficits? Can we target these disguised monocytes to improve the outcomes
of newborn brain injury?" said researcher Hong-Ru Chen, PhD, the first
author of the new study. "These are fascinating questions that beg for
more research."

========================================================================== Story Source: Materials provided by
University_of_Virginia_Health_System. Note: Content may be edited for
style and length.


========================================================================== Journal Reference:
1. Hong-Ru Chen, Yu-Yo Sun, Ching-Wen Chen, Yi-Min Kuo, Irena S. Kuan,
Zheng-Rong Tiger Li, Jonah C. Short-Miller, Marchelle
R. Smucker, Chia-Yi Kuan. Fate mapping via CCR2-CreER mice
reveals monocyte-to-microglia transition in development and
neonatal stroke. Science Advances, 2020; 6 (35): eabb2119 DOI:
10.1126/sciadv.abb2119 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/08/200831094723.htm

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