CCL17/CCR4 Axis Promotes Hematoma Clearance via ERK/AP1/SRA‐Mediated Microglial Polarization After Intracerebral Hemorrhage
CNS Neuroscience & Therapeutics,
Journal Year:
2025,
Volume and Issue:
31(2)
Published: Feb. 1, 2025
Our
previous
studies
demonstrated
that
CCL17
and
its
receptor
CCR4
play
crucial
roles
in
neuroinflammation
microglial
activation
following
intracerebral
hemorrhage
(ICH).
However,
the
specific
mechanisms
by
which
CCL17/CCR4
axis
regulates
polarization
hematoma
clearance
remain
unclear.
This
study
investigates
how
signaling
pathway
modulates
phenotype
transition
enhances
resolution
after
ICH,
building
upon
our
earlier
findings
showing
CCR4's
involvement
neuroinflammatory
responses.
Using
CRISPR-mediated
disruption
overexpression
approaches
a
mouse
ICH
model,
we
examined
neurological
outcomes,
inflammatory
responses,
volumes.
We
further
evaluated
therapeutic
potential
of
recombinant
administration.
The
downstream
ERK
pathway's
role
CCL17/CCR4-mediated
function
was
investigated
through
pharmacological
inhibition.
knockout
exacerbated
deficits,
increased
neuroinflammation,
enlarged
hematomas.
In
contrast,
enhancing
expression
or
administering
improved
functional
recovery
provided
neuroprotection.
Mechanistically,
activated
ERK/AP1/SRA
pathway,
promoting
anti-inflammatory,
phagocytic
polarization,
evidenced
CD206
SRA
expression.
inhibition
reversed
these
protective
effects.
extend
work
revealing
pathway-mediated
polarization.
mechanism
represents
promising
target
for
treatment.
Language: Английский
Combined Ionizing Radiation Exposure Improves Behavioral Symptoms and Modulates Brain Innate Immune System Activity in the Tau P301S Mice Line
Biochemistry (Moscow),
Journal Year:
2025,
Volume and Issue:
90(3), P. 400 - 412
Published: March 1, 2025
Language: Английский
Multiple Sclerosis: Glial Cell Diversity in Time and Space
Glia,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Dec. 24, 2024
ABSTRACT
Multiple
sclerosis
(MS)
is
the
most
prevalent
human
inflammatory
disease
of
central
nervous
system
with
demyelination
and
glial
scar
formation
as
pathological
hallmarks.
Glial
cells
are
key
drivers
lesion
progression
in
MS
roles
both
tissue
damage
repair
depending
on
surrounding
microenvironment
functional
state
individual
subtype.
In
this
review,
we
describe
recent
developments
context
cell
diversity
summarizing
findings
respect
to
maladaptive
functions
related
disease‐associated
subtypes.
A
particular
focus
spatial
temporal
dynamics
including
subtypes
microglia,
oligodendrocytes,
astrocytes.
We
contextualize
high‐dimensional
suggesting
that
dynamically
change
epigenomic,
transcriptomic,
metabolic
features
across
inflamed
rim
during
lesions.
summary,
detailed
knowledge
spatially
restricted
subtype
critical
for
a
better
understanding
pathology
its
pathogenesis
well
development
novel
therapies
targeting
specific
types.
Language: Английский