bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 24, 2024
Abstract
CNS-resident
microglia
and
recruited
myeloid
cells
populate
the
haematoma
in
intracerebral
haemorrhage
(ICH),
but
contribution
of
these
cell
populations
to
injury
repair
has
been
controversial.
To
better
characterise
changes
over
time,
we
employed
single-cell
RNA
sequencing
generate
a
unique
paired
dataset
live
peripheral
blood
samples
from
10
ICH
patients.
This
work
presents
temporal
atlas
identifies
population-specific
in-situ
transcriptional
drivers.
In
addition
distinct
activated
TNF-low
microglia,
found
highly
population
CD14
+
monocytes
haematoma.
Perturbation
analysis
comparing
haematoma-associated
shared
haematomas
identified
TNF
signalling
as
primary
driver
their
activation.
Employing
custom
trajectory
based
on
embeddings
foundation
model,
that
this
response
was
transient,
peaking
early
after
decreasing
ensuing
48
hours.
Our
further
transient
likely
source
during
acute
stage
ICH.
Acute
associated
with
adjusted
outcomes
both
our
external
cohorts.
Overall,
results
suggest
between
could
potentially
be
beneficial
recovery
One
sentence
summary
We
present
identify
dynamics.
British Journal of Pharmacology,
Год журнала:
2024,
Номер
181(18), С. 3303 - 3326
Опубликована: Май 15, 2024
Abstract
Background
and
Purpose
Amyotrophic
lateral
sclerosis
(ALS)
is
a
fatal
neurodegenerative
disorder
characterized
by
progressive
motor
neuron
(MN)
loss
consequent
muscle
atrophy,
for
which
no
effective
therapies
are
available.
Recent
findings
reveal
that
disease
progression
fuelled
early
aberrant
neuroinflammation
the
of
oligodendrocytes
with
neuroprotective
remyelinating
properties.
On
this
basis,
pharmacological
interventions
capable
restoring
pro‐regenerative
local
milieu
re‐establish
proper
oligodendrocyte
functions
may
be
beneficial.
Experimental
Approach
Here,
we
evaluated
in
vivo
therapeutic
effects
montelukast
(MTK),
an
antagonist
oligodendroglial
G
protein‐coupled
receptor
17
(GPR17)
cysteinyl‐leukotriene
1
(CysLT
R)
receptors
on
microglia
astrocytes,
SOD1
G93A
ALS
mouse
model.
We
chronically
treated
mice
MTK,
starting
from
symptomatic
stage.
Disease
was
assessed
behavioural
immunohistochemical
approaches.
Key
Results
Oral
MTK
treatment
significantly
extended
survival
probability,
delayed
body
weight
ameliorated
functionalityonly
female
mice.
Noteworthy,
restored
maturation
induced
significant
changes
reactive
phenotype
morphological
features
microglia/macrophages
astrocytes
spinal
cord
mice,
suggesting
enhanced
functions.
Importantly,
concomitant
MN
preservation
has
been
detected
after
administration.
No
beneficial
were
observed
male
highlighting
sex‐based
difference
protective
activity
MTK.
Conclusions
Implications
Our
results
provide
first
preclinical
evidence
indicating
repurposing
safe
marketed
anti‐asthmatic
drug,
promising
sex‐specific
strategy
personalized
treatment.
Antioxidants and Redox Signaling,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 2, 2025
Significance:
Damage
after
stroke
is
not
only
limited
to
the
brain
but
also
often
occurs
in
remote
organs,
including
heart,
lung,
liver,
kidney,
digestive
tract,
and
spleen,
which
are
frequently
affected
by
complex
pathophysiological
changes.
The
organs
human
body
closely
connected,
signals
transmitted
through
various
molecular
substances
could
regulate
changes
of
organs.
Recent
Advances:
latest
studies
have
shown
that
inflammatory
response
plays
an
important
role
organ
damage
stroke,
can
aggravate
activating
oxidative
stress,
sympathetic
axis,
hypothalamic
disturbing
immunological
homeostasis.
Remote
cause
brain,
aggravating
damage.
Critical
Issues:
Therefore,
in-depth
exploration
mechanisms
adopting
corresponding
comprehensive
intervention
strategies
become
necessary
reduce
promote
protection.
Future
Directions:
strategy
involves
multifaceted
treatment
methods
such
as
inflammation
regulation,
antioxidants,
neural
stem
cell
differentiation.
It
provides
a
promising
alternative
for
recovery
patients
inspiration
future
research
treatment.
interconnected
at
level.
Only
levels
we
save
protect
greatest
extent.
Antioxid.
Redox
Signal.
00,
000-000.
Frontiers in Immunology,
Год журнала:
2025,
Номер
16
Опубликована: Май 8, 2025
Astrocytes
play
a
pivotal
role
in
the
inflammatory
response
triggered
by
traumatic
brain
injury
(TBI).
They
are
not
only
involved
initial
following
but
also
significantly
contribute
to
Astrocyte
activation
and
inflammasome
release
key
processes
pathophysiology
of
TBI,
affecting
progression
secondary
long-term
outcomes.
This
comprehensive
review
explores
complex
triggering
mechanisms
astrocyte
intricate
pathways
controlling
inflammasomes
from
activated
astrocytes,
subsequent
neuroinflammatory
cascade
its
multifaceted
roles
after
injury.
The
exploration
these
deepens
our
understanding
highlights
potential
astrocytes
as
critical
therapeutic
targets
for
TBI
interventions.
We
then
evaluate
cutting-edge
research
aimed
at
targeted
approaches
modulate
pro-inflammatory
discuss
emerging
pharmacological
interventions
their
efficacy
preclinical
models.
Given
that
there
has
yet
be
relevant
elucidating
specific
intracellular
targeting
substances,
this
aims
provide
nuanced
astrocyte-mediated
neuroinflammation
elucidate
promising
avenues
could
fundamentally
change
management
improve
patient
development
neurological
sequelae.
By
releasing
variety
cytokines
chemokines,
regulate
neuroinflammation,
thereby
influencing
survival
function
surrounding
cells.
In
recent
years,
researchers
have
concentrated
efforts
on
signaling
crosstalk
between
other
cells
under
various
conditions,
while
exploring
paper
which
produce
mediators
during
acute
phase
post-TBI,
including
signaling,
blood-brain
barrier
integrity,
neuronal
protection.
Additionally,
we
current
clinical
intervention
strategies
mitigate
damage
enhance
recovery
TBI.
Finally,
explore
feasibility
pharmacologically
assessing
activity
post-TBI
biomarker
predicting
acute-phase
changes.
Frontiers in Bioscience-Landmark,
Год журнала:
2024,
Номер
29(9)
Опубликована: Сен. 24, 2024
Background:
The
polarization
of
macrophages
plays
a
critical
role
in
the
immune
response
to
infectious
diseases,
with
M2
shown
be
particularly
important
various
pathological
processes.
However,
specific
mechanisms
macrophage
Mycobacterium
tuberculosis
(Mtb)
infection
remain
unclear.
In
particular,
roles
Granulin
(GRN)
and
tumor
necrosis
factor
receptor
2
(TNFR2)
process
have
not
been
thoroughly
studied.
Objective:
To
investigate
effect
on
Mtb
mechanism
GRN
TNFR2
polarization.
Methods:
Forty
patients
pulmonary
(PTB)
40
healthy
volunteers
were
enrolled
this
study,
peripheral
blood
samples
taken
detect
levels
mRNA
by
Quantitative
Reverse
Transcription
Polymerase
Chain
Reaction
(RT-qPCR);
monocytes
isolated
then
assessed
Flow
Cytometry
(FC)
for
M1
levels.
further
validate
function
polarization,
we
used
interleukin
4
(IL-4)
induce
mouse
monocyte
RAW264.7
polarized
state.
expression
was
detected
Western
Blot
RT-qPCR.
Next,
constructed
knockdown
plasmid
transfected
it
into
IL-4-induced
RAW264.7,
TNFR2,
macrophage-associated
factors
factor-α
(TNF-α),
inducible
nitric
oxide
synthase
(iNOS),
6
(IL-6),
CD206,
IL-10,
Arginase
1
(Arg1);
Immunofluorescence
staining
monitor
CD86+
CD206+,
FC
analyze
phenotype.
Subsequently,
immunoprecipitation
binding
TNFR2.
Finally,
effects
explored
knocking
down
simultaneously
overexpressing
observing
status.
Results:
results
study
showed
elevated
predominance
type
PTB
compared
(p
<
0.05).
Moreover,
highly
expressed
Additionally,
followed
markers
TNF-α,
iNOS
IL-6
0.05),
decreased
polarization-associated
IL-10
Arg1
towards
M1.
found
that
binds
upregulates
addition,
marker
expression,
increased
macrophages,
whereas
concurrent
overexpression
macrophages.
Conclusion:
are
promotes
upregulating
expression.
