Stroke,
Год журнала:
2023,
Номер
54(7), С. 1888 - 1900
Опубликована: Июнь 15, 2023
BACKGROUND:
Intracerebral
hemorrhage
(ICH)
causes
severe
sensorimotor
dysfunction
and
cognitive
decline
which
are
aggravated
by
secondary
brain
injury,
yet
there
no
effective
management
to
alleviate
these
outcomes.
Pyroptosis
is
strongly
related
neuroinflammation,
plays
a
crucial
role
in
the
pathophysiological
processes
of
injury
after
ICH.
OXT
(oxytocin),
as
pleiotropic
neuropeptide,
has
multiple
functions
including
anti-inflammation
antioxidation.
This
study
aims
investigate
improving
ICH
outcomes
underlying
mechanisms.
METHODS:
C57BL/6
mice
were
used
establish
model
autologous
blood
injection.
was
administered
intranasally
(0.2
μg/g)
Combing
behavioral
tests,
Western
blot,
immunofluorescence
staining,
electron
microscopy,
pharmacological
approaches,
we
evaluated
effect
intranasal
application
on
neurological
explored
mechanism.
RESULTS:
Endogenous
level
decreased,
whereas
OXTR
(oxytocin
receptor)
expression
increased
treatment
improved
short-term
long-term
alleviated
neuronal
pyroptosis
neuroinflammation.
In
addition,
reduced
excessive
mitochondrial
fission
mitochondrial-derived
oxidative
stress
3
days
decreased
pyroptotic
proinflammatory
factors
NLRP3
(NOD-like
receptor
protein
3),
ASC
(apoptosis-associated
speck-like
containing
CARD),
GSDMD
(gasdermin
D),
caspase-1,
IL
(interleukin)-1β,
IL-18
p-PKA
(phospho-protein
kinase
A)
p-DRP1
(S637;
DRP1
[dynamin-related
1]
phosphorylation
at
Ser637).
OXT-induced
neuroprotective
effects
blocked
either
inhibitor
or
PKA
inhibitor.
CONCLUSIONS:
Intranasal
can
ameliorate
deficits
neural
pyroptosis,
inflammation,
via
OXTR/p-PKA/DRP1
signaling
pathway
Thus,
administration
may
be
potential
therapeutic
strategy
improve
prognosis
Brain Hemorrhages,
Год журнала:
2024,
Номер
5(3), С. 107 - 116
Опубликована: Янв. 20, 2024
Intracerebral
hemorrhage
(ICH)
is
a
severe
stroke
that
can
adversely
affect
patient
outcomes
due
to
the
accompanying
inflammatory
response.
As
result,
there
growing
interest
in
studying
inflammation
ICH.
We
systematically
reviewed
relevant
articles
using
Web
of
Science
understand
literature
on
this
subject.
This
study
aims
provide
comprehensive
overview
field
through
bibliometric
analysis,
highlight
its
current
status,
identify
frontiers,
and
speculate
future
directions.
conducted
analysis
global
English
related
ICH
research
based
from
1993
present
address
publication
trends
hotspots.
A
total
885
publications
were
included
2023.
These
authored
by
7,375
researchers
1,639
organizations
68
countries
published
571
journals.
Collectively,
they
cited
48,980
references
5,621
The
author
who
most
was
Dr.
Zhang,
John
H.
Interestingly,
6
top
ten
authors
China.
Regarding
articles,
China
at
list,
followed
United
States.
frequently
used
keywords
"Inflammation",
"Neuroinflammation",
"Microglia".
journal
reference
citations,
Stroke
journal.
Over
past
30
years,
has
been
considerable
progress
scientific
concerning
context
pivotal
themes
these
studies
have
immune
cells
mediators.
It
worth
noting,
however,
pertains
preclinical
studies,
with
comparatively
fewer
clinical
investigations.
Several
challenges
must
be
addressed
translate
promising
achievements
into
practice.
Frontiers in Immunology,
Год журнала:
2023,
Номер
14
Опубликована: Март 29, 2023
Mounting
evidence
indicates
that
inhibition
of
microglial
activation
and
neuronal
pyroptosis
plays
important
roles
in
brain
function
recovery
after
subarachnoid
hemorrhage
(SAH).
LDC7559
is
a
newly
discovered
gasdermin
D
(GSDMD)
inhibitor.
Previous
studies
have
demonstrated
could
inhibit
proliferation
pyroptosis.
However,
the
beneficial
effects
on
SAH
remain
obscure.
Based
this
background,
we
investigated
potential
role
mechanism
SAH-induced
damage
both
vivo
vitro
.
The
findings
revealed
were
evidently
increased
SAH,
which
be
markedly
suppressed
by
vitro.
Meanwhile,
treatment
reduced
apoptosis
improved
behavior
function.
Mechanistically,
decreased
levels
GSDMD
cleaved
SAH.
In
contrast,
nod-like
receptor
pyrin
domain-containing
3
(NLRP3)
inflammasome
nigericin
GSDMD-mediated
abated
damage.
did
not
significantly
affect
expression
NLRP3
Taken
together,
might
suppress
inhibiting
GSDMD,
thereby
promoting
functional
recovery.
Pharmacological Research,
Год журнала:
2023,
Номер
196, С. 106912 - 106912
Опубликована: Сен. 9, 2023
Microglia
are
first
responders
to
acute
brain
insults
and
initiate
neuroinflammation
drive
secondary
tissue
injury.
Yet
the
key
molecular
switches
in
control
of
inflammatory
activity
microglia
remain
poorly
understood.
Intracerebral
hemorrhage
(ICH)
is
a
devastating
stroke
subtype
whereby
hematoma
formed
within
parenchyma
associated
with
high
mortality.
Using
mouse
model
ICH,
we
found
upregulation
CD22
that
predominantly
occurred
microglia.
Antibody
blockade
led
reduction
neurological
deficits,
lesion
volume.
This
was
accompanied
by
reduced
activity,
increased
expression
alternative
activation
markers
(CD206
IL-10)
enhanced
phagocytosis
after
ICH.
also
an
increase
phosphorylated
SYK
AKT
Notably,
benefits
were
ablated
ICH
mice
subjected
microglial
depletion
colony-stimulating
factor
1
receptor
inhibitor
PLX5622.
Additionally,
protective
effects
diminished
receiving
R406.
Together,
our
findings
highlight
as
switch
detrimental
injury,
provide
novel
strategy
improve
outcome
Neural Regeneration Research,
Год журнала:
2024,
Номер
20(4), С. 1015 - 1030
Опубликована: Апрель 3, 2024
Cholesterol
is
an
important
component
of
plasma
membranes
and
participates
in
many
basic
life
functions,
such
as
the
maintenance
cell
membrane
stability,
synthesis
steroid
hormones,
myelination.
plays
a
key
role
establishment
central
nervous
system.
The
brain
contains
20%
whole
body’s
cholesterol,
80%
which
located
within
myelin.
A
huge
number
processes
(e.g.,
sterol
regulatory
element-binding
protein
pathway
liver
X
receptor
pathway)
participate
regulation
cholesterol
metabolism
via
mechanisms
that
include
biosynthesis,
intracellular
transport,
efflux.
Certain
injuries
or
diseases
involving
crosstalk
among
above
can
affect
normal
to
induce
detrimental
consequences.
Therefore,
we
hypothesized
cholesterol-related
molecules
pathways
serve
therapeutic
targets
for
system
diseases.
Intracerebral
hemorrhage
most
severe
hemorrhagic
stroke
subtype,
with
high
mortality
morbidity.
Historical
levels
are
associated
risk
intracerebral
hemorrhage.
Moreover,
secondary
pathological
changes
after
dysregulation,
neuroinflammation,
demyelination,
multiple
types
programmed
death.
Intracellular
accumulation
has
been
found
In
this
paper,
review
system,
known
disturbance
hemorrhage,
links
between
We
also
several
possible
constructive
identified
based
on
provide
cholesterol-based
perspectives
reference
those
interested
treatment
Neuropsychiatric Disease and Treatment,
Год журнала:
2024,
Номер
Volume 20, С. 83 - 99
Опубликована: Янв. 1, 2024
Objective:
The
aims
of
this
study
are
to
screen
novel
differentially
expressed
genes
(DEGs)
for
intracerebral
hemorrhage
(ICH)
and
reveal
the
role
Lipocalin-2
(LCN2)
in
ICH.
Methods:
We
constructed
ICH
model
by
injection
autologous
whole
blood
into
right
basal
ganglia
rats.
RNA-sequencing
bioinformatics
analyses
were
performed
identify
DEGs
between
sham
rats,
some
important
ones
confirmed
using
quantitative
real-time
PCR
(qRT-PCR).
LCN
shRNA
was
used
knockdown
LCN2
Pathological
examination
carried
out
2,3,5-triphenyltetrazolium
chloride
(TTC)
staining
Hematoxylin-eosin
(HE)
staining.
Immunohistochemistry
detected
Caspase-3,
co-staining
Terminal
dUTP
nick
end
labeling
(TUNEL)
NEUN
neuron
apoptosis
assessment.
Western
blot
analysis
quantify
pyroptosis-related
proteins.
Enzyme-linked
immunosorbent
assay
(ELISA)
measure
inflammatory
cytokine
levels.
Results:
rats
exhibited
significant
hematomas,
higher
brain
water
content,
obvious
interstitial
edema,
infiltration,
as
well
more
apoptotic
cells
tissues.
RNA-seq
identified
103
upregulated
81
downregulated
DEGs.
expression
LCN2,
HSPB1,
CXCL10,
MEF2B
triggered
release
interleukin
(IL)-1β,
tumor
necrosis
factor-α
(TNF-α),
IL-18,
promoted
proteins
Caspase-1,
GSDMD,
NLRP3,
ASC.
attenuated
pathological
characteristics
ICH,
also
reduced
pyroptosis
Conclusion:
Inhibition
attenuates
injury
after
via
suppressing
pyroptosis,
which
provide
guidance
management.
Keywords:
hemorrhage,
inflammation,
lipocalin-2
