CNS Neuroscience & Therapeutics,
Год журнала:
2023,
Номер
30(4)
Опубликована: Окт. 31, 2023
Abstract
Aims
Peripheral
immune
cells
infiltrating
into
the
brain
trigger
neuroinflammation
after
an
ischemic
stroke.
Partial
reprogram
their
function
for
neural
repair.
Which
promote
recovery
needs
further
identification.
Methods
We
performed
single‐cell
transcriptomic
profiling
of
CD45
high
isolated
from
hemisphere
at
subacute
(5
days)
and
chronic
(14
stages
Results
A
subset
phagocytic
macrophages
was
associated
with
neuron
projection
regeneration
tissue
remodeling.
also
identified
a
unique
type
T
highly
expressed
macrophage
markers,
including
C1q
,
Apoe
Hexb
Fcer1g
which
showed
abilities
in
remodeling,
myelination
regulation,
wound
healing,
anti‐neuroinflammation.
Moreover,
natural
killer
decreased
cytotoxicity
increased
energy
metabolic
stage
Two
subgroups
neutrophils
upregulated
CCL
signals
to
recruit
peripheral
released
CXCL2
keep
self‐recruiting
stage.
Conclusions
subsets
that
may
provide
potential
therapeutic
targets
promoting
poststroke
recovery.
Frontiers in Cellular Neuroscience,
Год журнала:
2022,
Номер
16
Опубликована: Авг. 16, 2022
Stroke
remains
a
major
cause
of
long-term
disability
and
mortality
worldwide.
The
immune
system
plays
an
important
role
in
determining
the
condition
brain
following
stroke.
As
resident
innate
cells
central
nervous
system,
microglia
are
primary
responders
defense
network
covering
entire
parenchyma,
exert
various
functions
depending
on
dynamic
communications
with
neurons,
astrocytes,
other
neighboring
under
both
physiological
or
pathological
conditions.
Microglia
activation
polarization
is
crucial
for
damage
repair
ischemic
stroke,
considered
double-edged
sword
neurological
recovery.
can
exist
pro-inflammatory
states
promote
secondary
damage,
but
they
also
secrete
anti-inflammatory
cytokines
neurotrophic
factors
facilitate
recovery
In
this
review,
we
focus
mechanisms
microglia-mediated
neuroinflammation
neuroplasticity
after
ischemia
relevant
potential
microglia-based
interventions
stroke
therapy.
Science Translational Medicine,
Год журнала:
2024,
Номер
16(733)
Опубликована: Фев. 7, 2024
Neuroinflammation
is
acknowledged
as
a
pivotal
pathological
event
after
cerebral
ischemia.
However,
there
limited
knowledge
of
the
molecular
and
spatial
characteristics
nonneuronal
cells,
well
interactions
between
cell
types
in
ischemic
brain.
Here,
we
used
transcriptomics
to
study
hemisphere
mice
stroke
sequenced
transcriptomes
19,777
spots,
allowing
us
both
visualize
transcriptional
landscape
within
tissue
identify
gene
expression
profiles
linked
specific
histologic
entities.
Cell
identified
by
single-cell
RNA
sequencing
confirmed
enriched
annotation
ischemia-associated
peri-infarct
area
hemisphere.
Analysis
ligand-receptor
communication
revealed
galectin-9
cell-surface
glycoprotein
CD44
(LGALS9-CD44)
critical
signaling
pathway
injury
microglia
macrophages
main
source
galectins
stroke.
Extracellular
vesicle–mediated
Lgals9
delivery
improved
long-term
functional
recovery
photothrombotic
mice.
Knockdown
Cd44
partially
reversed
these
therapeutic
effects,
inhibiting
oligodendrocyte
differentiation
remyelination.
In
summary,
our
provides
detailed
cellular
characterization
peri-infact
murine
model
potential
treatment
target
that
warrants
further
investigation.
Glia,
Год журнала:
2024,
Номер
72(6), С. 1016 - 1053
Опубликована: Янв. 4, 2024
Abstract
Microglia
play
key
roles
in
the
post‐ischemic
inflammatory
response
and
damaged
tissue
removal
reacting
rapidly
to
disturbances
caused
by
ischemia
working
restore
lost
homeostasis.
However,
modified
environment,
encompassing
ionic
imbalances,
disruption
of
crucial
neuron–microglia
interactions,
spreading
depolarization,
generation
danger
signals
from
necrotic
neurons,
induce
morphological
phenotypic
shifts
microglia.
This
leads
them
adopt
a
proinflammatory
profile
heighten
their
phagocytic
activity.
From
day
three
post‐ischemia,
macrophages
infiltrate
core
while
microglia
amass
at
periphery.
Further,
inflammation
prompts
metabolic
shift
favoring
glycolysis,
pentose‐phosphate
shunt,
lipid
synthesis.
These
shifts,
combined
with
intake,
drive
droplet
biogenesis,
fuel
anabolism,
enable
proliferation.
Proliferating
release
trophic
factors
contributing
protection
repair.
some
accumulate
lipids
persistently
transform
into
dysfunctional
potentially
harmful
foam
cells.
Studies
also
showed
that
either
display
impaired
apoptotic
cell
clearance,
or
eliminate
synapses,
viable
endothelial
Yet,
it
will
be
essential
elucidate
viability
engulfed
cells,
features
local
extent
damage,
temporal
sequence.
Ischemia
provides
rich
variety
region‐
injury‐dependent
stimuli
for
microglia,
evolving
time
generating
distinct
phenotypes
including
those
exhibiting
traits
others
showing
pro‐repair
features.
Accurate
profiling
phenotypes,
alongside
more
precise
understanding
associated
conditions,
is
necessary
step
serve
as
potential
foundation
focused
interventions
human
stroke.
Frontiers in Immunology,
Год журнала:
2022,
Номер
13
Опубликована: Ноя. 16, 2022
Ischemic
stroke
(IS)
is
one
of
the
major
types
cerebrovascular
diseases
causing
neurological
morbidity
and
mortality
worldwide.
In
pathophysiological
process
IS,
microglia
play
a
beneficial
role
in
tissue
repair.
However,
it
could
also
cause
cellular
damage,
consequently
leading
to
cell
death.
Inflammation
characterized
by
activation
microglia,
increasing
evidence
showed
that
autophagy
interacts
with
inflammation
through
regulating
correlative
mediators
signaling
pathways.
this
paper,
we
summarized
harmful
effects
IS.
addition,
discussed
interplay
between
ischemic
inflammation,
as
along
its
application
treatment
We
believe
help
provide
theoretical
references
for
further
study
into
IS
treatments
future.
Abstract
The
intervertebral
disc
(IVD)
acts
as
a
fibrocartilaginous
joint
to
anchor
adjacent
vertebrae.
Although
several
studies
have
demonstrated
the
cellular
heterogeneity
of
adult
mature
IVDs,
single‐cell
transcriptomic
atlas
mapping
early
IVD
formation
is
still
lacking.
Here,
authors
generate
spatiotemporal
and
single
cell‐based
human
at
embryonic
stage
comparative
mouse
transcript
landscape.
They
identify
two
novel
notochord
(NC)/nucleus
pulposus
(NP)
clusters,
SRY‐box
transcription
factor
10
(SOX10)
+
cathepsin
K
(CTSK)
,
that
are
distributed
in
late
stages
they
validated
by
lineage
tracing
experiments
mice.
Matrisome
NC/NP
T‐box
T
(TBXT)
CTSK
responsible
for
extracellular
matrix
homeostasis.
suggests
subcluster
vertebral
chondrocyte
might
give
rise
an
inner
annulus
fibrosus
chondrogenic
origin,
while
fibroblastic
outer
preferentially
expresseds
transgelin
fibromodulin
.
Through
analyzing
intercellular
crosstalk,
further
find
notochordal
secreted
phosphoprotein
1
(SPP1)
cue
microenvironment,
it
associated
with
development
degeneration.
In
conclusion,
will
be
leveraged
develop
preventative
regenerative
strategies
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Июль 24, 2024
Neuroglia
critically
shape
the
brain´s
response
to
ischemic
stroke.
However,
their
phenotypic
heterogeneity
impedes
a
holistic
understanding
of
cellular
composition
early
lesion.
Here
we
present
single
cell
resolution
transcriptomics
dataset
acute
infarction.
Oligodendrocyte
lineage
cells
and
astrocytes
range
among
most
transcriptionally
perturbed
populations
exhibit
infarction-
subtype-specific
molecular
signatures.
Specifically,
find
infarction
restricted
proliferating
oligodendrocyte
precursor
(OPCs),
mature
oligodendrocytes
reactive
astrocytes,
exhibiting
transcriptional
commonalities
in
injury.
OPCs
are
involved
shared
immuno-glial
cross
talk
with
stroke-specific
myeloid
cells.
Within
perilesional
zone,
osteopontin
positive
accumulate
close
proximity
CD44
Journal of Neuroinflammation,
Год журнала:
2022,
Номер
19(1)
Опубликована: Май 16, 2022
Microglia/macrophages
are
activated
after
cerebral
ischemic
stroke
and
can
contribute
to
either
brain
injury
or
recovery
by
polarizing
microglia/macrophage
into
distinctive
functional
phenotypes
with
pro-
anti-inflammatory
properties.
Interleukin-13
(IL-13)
is
an
cytokine
that
regulates
polarization
toward
phenotype.
However,
it
not
clear
whether
IL-13
beneficial
long-term
the
underlying
molecular
mechanism(s)
remain
unknown.
Thus,
we
examined
effect
of
on
in
mice
transient
middle
artery
occlusion
model
(tMCAO).tMCAO
was
induced
adult
male
C57BL/6J
mice.
(60
μg/kg)
administered
intranasally
starting
2
h
continued
for
seven
consecutive
days.
Sensorimotor
function,
spatial
learning
memory
as
well
infarct
volume
were
assessed
up
35
days
stroke.
White
matter
integrity
evaluated
electrophysiology,
immunofluorescence
staining,
transmission
electron
microscopy.
Microglia/macrophage
activation
using
staining
quantitative
real-time
polymerase
chain
reaction.
Changes
immune
cells
periphery,
expression
receptors
different
detected
flow
cytometry.
Primary
neuron/microglia
co-cultures
a
STAT3
inhibitor
used
mechanistic
studies.Post-treatment
improved
neurofunctional
decreased
tissue
atrophy
Intranasal
delivery
enhanced
structural
white
Furthermore,
neuroprotection
afforded
administration
due
direct
neurons,
but
indirectly
regulating
phenotype
microglia/macrophages.
treatment
also
had
no
peripheral
cells.
Mechanistically,
outcome
promoting
microglia/macrophages
at
least
partially
inhibiting
phosphorylation
STAT3.IL-13
promotes
repair
improves
outcomes
modulating
via
inhibition
phosphorylation.