Biomedicine & Pharmacotherapy,
Год журнала:
2023,
Номер
168, С. 115653 - 115653
Опубликована: Окт. 7, 2023
The
modulation
of
microglial
polarization
from
the
pro-inflammatory
M1
to
anti-inflammatory
M2
phenotype
shows
promise
as
a
therapeutic
strategy
for
ischemic
stroke.
Quercetin,
natural
flavonoid
abundant
in
various
plants,
possesses
anti-inflammatory,
anti-apoptotic,
and
antioxidant
properties.
Nevertheless,
its
effect
underlying
mechanism
on
microglia/macrophages
M1/M2
treatment
cerebral
ischemia/reperfusion
injury
(CI/RI)
remain
poorly
explored.
In
current
study,
we
observed
that
quercetin
ameliorated
neurological
deficits,
reduced
infarct
volume,
decreased
number
(CD16/32+/Iba1+),
enhanced
(CD206+/Iba1+)
after
establishing
CI/RI
model
rats.
Subsequent
vivo
vitro
experiments
indicated
downregulated
markers
(CD86,
iNOS,
TNF-α,
IL-1β,
IL-6)
upregulated
(CD206,
Arg-1,
IL-10,
TGF-β).
Network
pharmacology
analysis
molecular
docking
revealed
PI3K/Akt/NF-κB
signaling
pathway
emerged
core
pathway.
Western
blot
confirmed
phosphorylation
PI3K
Akt,
while
alleviating
IκBα
NF-κB
both
vitro.
However,
inhibitor
LY294002
reversed
effects
expression
key
proteins
primary
microglia
oxygen-glucose
deprivation/reoxygenation
(OGD/R)
Collectively,
our
findings
demonstrate
facilitates
by
modulating
CI/RI.
These
provide
novel
insights
into
mechanisms
Pharmacological Research,
Год журнала:
2024,
Номер
206, С. 107300 - 107300
Опубликована: Июль 9, 2024
Depression
is
a
serious
global
mental
disorder.
Numerous
studies
have
found
that
depression
may
be
closely
related
to
decreased
neurogenesis,
neuroinflammation,
neurotransmitter
imbalance,
and
synaptic
plasticity
dysfunction.
The
pathogenesis
of
complex
involves
multiple
signal
transduction
pathways
molecular
changes.
PI3K/AKT
pathway
an
essential
signaling
in
neurons,
which
widely
expressed
emotion-related
regions
the
brain.
Therefore,
play
moderating
role
mood
disorders.
However,
mechanism
not
been
fully
described.
This
review
systematically
summarized
discussed
its
potential
treatment
depression.
will
help
development
antidepressants.
Translational Stroke Research,
Год журнала:
2024,
Номер
unknown
Опубликована: Май 14, 2024
Abstract
Stroke
in
China
is
distinguished
by
its
high
rates
of
morbidity,
recurrence,
disability,
and
mortality.
The
ultra-early
administration
rtPA
essential
for
restoring
perfusion
acute
ischemic
stroke,
though
it
concurrently
elevates
the
risk
hemorrhagic
transformation.
High-mobility
group
box
1
(HMGB1)
emerges
as
a
pivotal
player
neuroinflammation
after
brain
ischemia
ischemia–reperfusion.
Released
passively
necrotic
cells
actively
secreted,
including
direct
secretion
HMGB1
into
extracellular
space
packaging
intracellular
vesicles
immune
cells,
glial
platelets,
endothelial
represents
prototypical
damage-associated
molecular
pattern
(DAMP).
It
intricately
involved
pathogenesis
atherosclerosis,
thromboembolism,
detrimental
inflammation
during
early
phases
stroke.
Moreover,
significantly
contributes
to
neurovascular
remodeling
functional
recovery
later
stages.
Significantly,
mediates
transformation
facilitating
neuroinflammation,
directly
compromising
integrity
blood–brain
barrier,
enhancing
MMP9
through
interaction
with
rtPA.
As
systemic
inflammatory
factor,
also
implicated
post-stroke
depression
an
elevated
stroke-associated
pneumonia.
role
extends
influencing
polarizing
various
subtypes
cells.
This
includes
mediating
excitotoxicity
due
excitatory
amino
acids,
autophagy,
release,
NET
formation,
autocrine
trophic
pathways.
Given
multifaceted
role,
recognized
crucial
therapeutic
target
prognostic
marker
stroke
In
this
review,
we
summarize
structure
redox
properties,
pathways,
regulation
cell
activity,
pathophysiological
mechanisms
hemorrhage
HMGB1,
which
will
pave
way
developing
new
neuroprotective
drugs,
reduction
expansion
thrombolysis
time
window.
Journal of Clinical Medicine,
Год журнала:
2025,
Номер
14(2), С. 386 - 386
Опубликована: Янв. 9, 2025
The
blood-brain
barrier
(BBB)
is
a
crucial
structure
that
maintains
brain
homeostasis
by
regulating
the
entry
of
molecules
and
cells
from
bloodstream
into
central
nervous
system
(CNS).
Neurodegenerative
diseases
such
as
Alzheimer's
Parkinson's
disease,
well
ischemic
stroke,
compromise
integrity
BBB.
This
leads
to
increased
permeability
infiltration
harmful
substances,
thereby
accelerating
neurodegeneration.
In
this
review,
we
explore
mechanisms
underlying
BBB
disruption,
including
oxidative
stress,
neuroinflammation,
vascular
dysfunction,
loss
tight
junction
integrity,
in
patients
with
neurodegenerative
diseases.
We
discuss
how
breakdown
contributes
neurotoxicity,
abnormal
accumulation
pathological
proteins,
all
which
exacerbate
neuronal
damage
facilitate
disease
progression.
Furthermore,
potential
therapeutic
strategies
aimed
at
preserving
or
restoring
function,
anti-inflammatory
treatments,
antioxidant
therapies,
approaches
enhance
integrity.
Given
role
neurodegeneration,
maintaining
its
represents
promising
approach
slow
prevent
progression
Journal of Neuroinflammation,
Год журнала:
2025,
Номер
22(1)
Опубликована: Янв. 21, 2025
Abstract
Central
nervous
system
(CNS)
injuries,
such
as
ischemic
stroke
(IS),
intracerebral
hemorrhage
(ICH)
and
traumatic
brain
injury
(TBI),
are
a
significant
global
burden.
The
complex
pathophysiology
of
CNS
is
comprised
primary
secondary
injury.
Inflammatory
incited
by
damage-associated
molecular
patterns
(DAMPs)
which
signal
variety
resident
cells
infiltrating
immune
cells.
Extracellular
cold-inducible
RNA-binding
protein
(eCIRP)
DAMP
acts
through
multiple
non-immune
to
promote
inflammation.
Despite
the
well-established
role
eCIRP
in
systemic
sterile
inflammation,
its
less
elucidated.
Recent
literature
suggests
that
pleiotropic
inflammatory
mediator
also
being
evaluated
clinical
biomarker
indicate
prognosis
injuries.
This
review
provides
broad
overview
injury,
with
focus
on
immune-mediated
neuroinflammation.
We
then
what
known
about
mechanisms
both
non-CNS
cells,
identifying
opportunities
for
further
study.
explore
eCIRP’s
potential
prognostic
marker
severity
outcome.
Next,
we
provide
an
eCIRP-targeting
therapeutics
suggest
strategies
develop
these
agents
ameliorate
Finally,
emphasize
exploring
novel
mechanisms,
aside
from
neuroinflammation,
critical
therapeutic
target
International Journal of Molecular Sciences,
Год журнала:
2023,
Номер
24(19), С. 14771 - 14771
Опубликована: Сен. 30, 2023
The
neuroinflammatory
response
after
intracerebral
hemorrhage
(ICH)
causes
a
large
amount
of
neuronal
loss,
and
inhibiting
the
inflammatory
can
improve
prognosis.
In
previous
laboratory
studies
clinical
trials,
ursolic
acid
(UA)
inhibited
response,
but
whether
it
be
administered
to
inhibit
cerebral
is
unknown.
aim
this
study
was
investigate
effects
hemorrhage.
Online
databases
were
used
obtain
potential
therapeutic
targets
for
treatment
hemorrhage,
possible
mechanisms
analyzed
by
KEGG,
GO,
molecular
docking.
A
rat
model
established
using
collagenase,
an
in
vitro
constructed
adding
hemin
BV2
cell
culture
medium.
Enzyme-linked
immunosorbent
assay
(ELISA),
Western
blotting
(WB),
immunofluorescence,
TUNEL
staining,
calcein/PI
staining
degree
microglial
M1
polarization,
changes
levels
factors,
activation
NF-κB
pathway,
indicators
cellular
death
treatment.
addition,
phorbol
12-myristate
13-acetate
(PMA)
activate
pathway
verify
that
exerts
its
anti-neuroinflammatory
regulating
NF-κB/NLRP3/GSDMD
pathway.
Network
pharmacology
bioinformatics
analyses
revealed
may
exert
on
through
multiple
pathways.
Together,
vivo
experiments
showed
polarization
significantly
reduced
p-NF-κB,
GSDMD-N,
cleaved
caspase-1,
TNF-α,
IL-6,
IL-1β,
which
use
PMA.
Ursolic
inhibits
pyroptosis
via
alleviate
responses
Journal of Neuroinflammation,
Год журнала:
2024,
Номер
21(1)
Опубликована: Янв. 29, 2024
Microglia
is
the
major
contributor
of
post-stroke
neuroinflammation
cascade
and
crucial
cellular
target
for
treatment
ischemic
stroke.
Currently,
endogenous
mechanism
underlying
microglial
activation
following
stroke
remains
elusive.
Serglycin
(SRGN)
a
proteoglycan
expressed
in
immune
cells.
Up
to
now,
role
SRGN
on
largely
unexplored.
ACS Nano,
Год журнала:
2024,
Номер
18(26), С. 16450 - 16467
Опубликована: Июнь 19, 2024
Nanozymes,
which
can
selectively
scavenge
reactive
oxygen
species
(ROS),
have
recently
emerged
as
promising
candidates
for
treating
ischemic
stroke
and
traumatic
brain
injury
(TBI)
in
preclinical
models.
ROS
overproduction
during
the
early
phase
of
these
diseases
leads
to
oxidative
damage,
has
been
a
major
cause
mortality
worldwide.
However,
clinical
application
ROS-scavenging
enzymes
is
limited
by
their
short
vivo
half-life
inability
cross
blood-brain
barrier.
mimic
catalytic
function
natural
enzymes,
several
advantages,
including
cost-effectiveness,
high
stability,
easy
storage.
These
advantages
render
them
superior
disease
diagnosis
therapeutic
interventions.
This
review
highlights
recent
advancements
nanozyme
applications
TBI,
emphasizing
potential
mitigate
detrimental
effect
overproduction,
inflammation,
barrier
compromise.
Therefore,
nanozymes
represent
treatment
modality
conditions
future
medical
practices.
CNS Neuroscience & Therapeutics,
Год журнала:
2024,
Номер
30(5)
Опубликована: Май 1, 2024
Stroke
is
an
acute
cerebrovascular
disease
in
which
brain
tissue
damaged
due
to
sudden
obstruction
of
blood
flow
the
or
rupture
vessels
brain,
can
prompt
ischemic
hemorrhagic
stroke.
After
stroke
onset,
ischemia,
hypoxia,
infiltration
components
into
parenchyma,
and
lysed
cell
fragments,
among
other
factors,
invariably
increase
blood-brain
barrier
(BBB)
permeability,
inflammatory
response,
edema.
These
changes
lead
neuronal
death
synaptic
dysfunction,
latter
poses
a
significant
challenge
treatment.
