Glia,
Год журнала:
2023,
Номер
71(7), С. 1648 - 1666
Опубликована: Март 24, 2023
Abstract
Reactive
astrocytes
can
be
transformed
into
new
neurons.
Vascular
endothelial
growth
factor
(VEGF)
promotes
the
transformation
of
reactive
neurons
in
ischemic
brain.
Therefore,
this
study,
molecular
mechanism
VEGF's
effect
on
ischemia/hypoxia‐induced
astrocyte
to
neuron
was
investigated
models
rat
middle
cerebral
artery
occlusion
(MCAO)
and
culture
with
oxygen
glucose
deprivation
(OGD).
We
found
that
VEGF
enhanced
ischemia‐induced
Pax6,
a
neurogenic
fate
determinant,
expression
Erk
phosphorylation
reduced
infarct
volume
brain
at
3
days
after
MCAO,
which
effects
could
blocked
by
administration
U0126,
MAPK/Erk
inhibitor.
In
cultured
astrocytes,
also
OGD‐induced
Pax6
expression,
but
not
wortmannin,
PI3K/Akt
inhibitor,
or
SB203580,
MAPK/p38
suggesting
via
activation
pathway.
OGD
induced
increase
miR365
inhibited
expression.
However,
agonists
VEGF‐enhanced
hypoxic
did
block
phosphorylation.
further
promoted
astrocyte‐converted
neuron.
Interestingly,
both
U0126
RNAi
significantly
enhancement
astrocytes‐to‐neurons
transformation,
as
indicated
Dcx
MAP2
immunopositive
signals
astrocytes.
Moreover,
those
become
mature
functional.
concluded
astrocytic
neurogenesis
MAPK/Erk‐miR‐365‐Pax6
signal
axis.
The
results
play
important
roles
reconstruction
neurovascular
units
stroke.
Journal of Pharmaceutical Analysis,
Год журнала:
2023,
Номер
13(2), С. 156 - 169
Опубликована: Янв. 7, 2023
Stroke
is
the
second
leading
cause
of
death
worldwide,
and
oxidative
stress
plays
a
crucial
role.
Celastrol
exhibits
strong
antioxidant
properties
in
several
diseases;
however,
whether
it
can
affect
oxidation
cerebral
ischemic-reperfusion
injury
(CIRI)
remains
unclear.
This
study
aimed
to
determine
celastrol
could
reduce
damage
during
CIRI
elucidate
underlying
mechanisms.
Here,
we
found
that
attenuated
by
upregulating
nuclear
factor
E2-related
2
(Nrf2).
Using
alkynyl-tagged
liquid
chromatography-tandem
mass
spectrometry,
showed
directly
bound
neuronally
expressed
developmentally
downregulated
4
(Nedd4)
then
released
Nrf2
from
Nedd4
astrocytes.
promoted
degradation
through
K48-linked
ubiquitination
thus
contributed
astrocytic
reactive
oxygen
species
production
CIRI,
which
was
significantly
blocked
celastrol.
Furthermore,
inhibiting
astrocyte
activation,
effectively
rescued
neurons
axon
apoptosis.
Our
uncovered
as
direct
target
celastrol,
exerts
an
antioxidative
effect
on
astrocytes
interaction
between
reducing
CIRI.
Frontiers in Molecular Neuroscience,
Год журнала:
2023,
Номер
16
Опубликована: Март 23, 2023
Glutamate
plays
an
important
role
in
excitotoxicity
and
ferroptosis.
Excitotoxicity
occurs
through
over-stimulation
of
glutamate
receptors,
specifically
NMDAR,
while
the
non-receptor-mediated
pathway,
high
concentrations
reduce
cystine
uptake
by
inhibiting
System
Xc-,
leading
to
intracellular
glutathione
depletion
resulting
ROS
accumulation,
which
contributes
increased
lipid
peroxidation,
mitochondrial
damage,
ultimately
Oxidative
stress
appears
crosstalk
between
ferroptosis,
it
is
essential
maintain
homeostasis
inhibit
oxidative
responses
vivo
.
As
researchers
work
develop
natural
compounds
further
investigate
complex
mechanisms
regulatory
functions
ferroptosis
excitotoxicity,
new
avenues
will
be
available
for
effective
treatment
ischaemic
stroke.
Therefore,
this
paper
provides
a
review
molecular
glutamate-mediated
Biomedicines,
Год журнала:
2023,
Номер
11(1), С. 223 - 223
Опубликована: Янв. 16, 2023
Acute
spontaneous
intracerebral
hemorrhage
(ICH)
is
the
most
severe
stroke
subtype,
with
a
high
risk
of
death,
dependence,
and
dementia.
Knowledge
about
clinical
profile
early
outcomes
ICH
patients
lobar
versus
deep
subcortical
brain
topography
remains
limited.
In
this
study,
we
investigated
effects
on
demographics,
cerebrovascular
factors,
characteristics,
in
sample
298
consecutive
acute
(165
133
hemorrhagic
stroke)
available
single-center-based
registry
over
24
years.
The
multiple
logistic
regression
analysis
shows
that
variables
independently
associated
were
seizures
(OR
6.81,
CI
95%
1.27−5.15),
chronic
liver
disease
4.55,
1.03−20.15),
hemianopia
2.55,
1.26−5.15),
headaches
1.90,
IC
1.06−3.41),
alcohol
abuse
(>80
gr/day)
0−10,
0.02−0,53),
hypertension
0,41,
0.23−0−70),
sensory
deficit
0.43,
0.25−0.75),
limb
weakness
(OR:
0.47,
0.24−0.93).
in-hospital
mortality
was
26.7%
for
16.5%
ICH.
study
confirmed
spectrum,
prognosis,
depend
site
bleeding,
more
prognosis
hemorrhage.
Cell Biology and Toxicology,
Год журнала:
2024,
Номер
40(1)
Опубликована: Фев. 2, 2024
Abstract
Background
Stroke
is
a
major
medical
problem,
and
novel
therapeutic
targets
are
urgently
needed.
This
study
investigates
the
protective
role
potential
mechanisms
of
N6-methyladenosine
(m6A)
RNA
methyltransferase
METTL3
against
cerebral
injury
resulting
from
insufficient
blood
flow.
Methods
In
this
study,
we
constructed
mouse
MCAO
models
HT-22
cell
OGD/R
to
mimic
ischemic
stroke-induced
brain
neuronal
damage.
We
generated
NEDD4L
knockout
overexpression
validated
effects
using
infarct
volume,
edema,
neurologic
scoring.
performed
qRT-PCR,
western
blotting,
co-immunoprecipitation
assess
influence
on
ferroptosis
markers
TFRC
expression.
verified
effect
ubiquitination
by
detecting
half-life
ubiquitination.
Finally,
impact
mRNA
stability
outcomes
in
both
vitro
vivo
experimental
models.
Result
find
expression
downregulated
Overexpressing
inhibits
iron
carrier
protein
upregulating
E3
ubiquitin
ligase
NEDD4L,
thereby
alleviating
oxidative
damage
protect
injury.
Mechanistic
studies
show
can
methylate
stabilize
mRNA,
enhancing
As
downstream
effector,
ubiquitinates
degrades
TFRC,
reducing
accumulation
ferroptosis.
Conclusion
summary,
uncover
METTL3-NEDD4L-TFRC
axis
critical
for
inhibiting
post-ischemic
Enhancing
pathway
may
serve
as
an
effective
strategy
stroke
therapy.
lays
theoretical
foundation
developing
m6A-related
therapies
Biomedicines,
Год журнала:
2024,
Номер
12(3), С. 501 - 501
Опубликована: Фев. 23, 2024
Stroke
is
a
major
contributor
to
global
mortality
and
disability.
While
reperfusion
essential
for
preventing
neuronal
death
in
the
penumbra,
it
also
triggers
cerebral
ischemia-reperfusion
injury,
paradoxical
injury
primarily
caused
by
oxidative
stress,
inflammation,
blood–brain
barrier
disruption.
An
burst
inflicts
marked
cellular
damage,
ranging
from
alterations
mitochondrial
function
lipid
peroxidation
activation
of
intricate
signalling
pathways
that
can
even
lead
cell
death.
Thus,
given
pivotal
role
stress
mechanisms
reinforcement
antioxidant
defence
system
has
been
proposed
as
protective
approach.
Although
this
strategy
proven
be
successful
experimental
models,
its
translation
into
clinical
practice
yielded
inconsistent
results.
However,
should
considered
availability
numerous
molecules
with
wide
range
chemical
properties
affect
extent
injury;
several
groups
molecules,
including
polyphenols,
carotenoids,
vitamins,
among
other
compounds,
mitigate
damage
intervening
multiple
at
various
stages.
Multiple
trials
have
previously
conducted
evaluate
these
using
melatonin,
acetyl-L-carnitine,
chrysanthemum
extract,
edaravone
dexborneol,
saffron,
coenzyme
Q10,
oleoylethanolamide,
treatments.
Therefore,
multi-antioxidant
therapy
emerges
promising
novel
therapeutic
option
due
potential
synergistic
effect
provided
simultaneous
roles
individual
compounds.
