Frontiers in Neurology,
Год журнала:
2025,
Номер
16
Опубликована: Март 17, 2025
Mitochondrial
dysfunction
and
ferroptosis
have
been
implicated
in
the
pathophysiological
processes
following
spinal
cord
injury
(SCI),
with
evidence
suggesting
their
interplay
influences
neuronal
cell
survival
repair
mechanisms.
This
study
seeks
to
identify
mitochondria-
ferroptosis-related
biomarkers
through
comprehensive
bioinformatics
analysis.
Mitochondria-
ferroptosis-associated
differentially
expressed
genes
(DEGs)
were
identified
integration
of
differential
expression
analysis
weighted
gene
co-expression
network
Two
machine
learning
algorithms,
least
absolute
shrinkage
selection
operator
(LASSO)
Boruta,
employed
isolate
SCI-associated
feature
genes.
Biomarkers
subsequently
by
analyzing
levels.
An
artificial
neural
(ANN)
diagnostic
model
was
constructed
predict
SCI
likelihood
based
on
these
biomarkers.
Further
evaluations
performed
using
enrichment
analysis,
immune
infiltration
profiling,
molecular
modulation
assessment,
drug
prediction.
The
biomarkers'
levels
validated
RT-qPCR.
In
this
study,
two
biomarkers,
Hcrt
Cdca2,
linked
mitochondrial
function
SCI,
found
be
highly
samples.
Tissue-specific
from
GTEx
database
revealed
brain
tissues.
ANN
model,
accurately
discriminated
between
control
Enrichment
highlighted
several
co-enriched
pathways
for
including
"ubiquitin-mediated
proteolysis,"
"endocytosis,"
"neurotrophin
signaling
pathway."
Immune
Wilcoxon
test,
demonstrated
significant
differences
T
follicular
helper
levels,
which
lower
samples
compared
controls.
Notably,
cells
exhibited
a
positive
correlation
negative
Cdca2.
Furthermore,
seven
transcription
factors,
CEBPB,
FOXC1,
GATA2,
as
potential
co-regulators
Drug
prediction
stable
interactions
Cdca2
pinosylvin,
zinc
acetate
dihydrate,
hydroquinone,
lucanthone,
dasatinib.
RT-qPCR
validation
confirmed
patterns
alignment
dataset,
showing
statistically
differences.
identifies
related
providing
new
insights
diagnosis
mechanistic
understanding
SCI.
Frontiers in Immunology,
Год журнала:
2022,
Номер
13
Опубликована: Сен. 26, 2022
Neuroinflammation
following
spinal
cord
injury
(SCI)
results
in
prolonged
neurological
damage
and
locomotor
dysfunction.
Polarization
of
microglia
is
vital
to
regulation
neuroinflammation,
although
the
underlying
mechanisms
have
not
yet
been
elucidated.
Endocannabinoid
receptor
subtype
2
(CB2R)
reported
ameliorate
neurodegeneration
via
immunomodulation
activities.
However,
machinery
context
SCI
remains
unclear.A
lipopolysaccharide-induced
inflammation
model
a
mouse
were
employed
investigate
regulatory
role
CB2R
polarization
response
excess
neuroinflammation.
Markers
autophagy
measured
by
Western
blot
analysis,
immunofluorescence,
flow
cytometry,
enzyme-linked
immunosorbent
assays.
Histological
staining
with
hematoxylin
eosin,
Nissl,
Luxol®
fast
blue
was
conducted
using
commercial
kits.
The
function
hindlimbs
experimental
mice
evaluated
Basso
Mouse
Scale,
Louisville
Swim
footprint
assay.The
showed
that
promoted
M2
differentiation,
increased
interleukin
(IL)-10
expression,
inhibited
M1
differentiation
decreased
expression
IL-1β
IL-6.
activation
also
ubiquitination
NLRP3
inflammasome
interacted
autophagy-related
proteins
p62
microtubule-associated
1B
light
chain
3.
Treatment
activator
JWH-133
reduced
loss
myelin,
apoptosis
neurons,
glial
scarring,
leading
improved
functional
recovery
hindlimbs,
while
antagonist
AM630
produced
opposite
results.Taken
together,
these
suggested
attenuated
neuroinflammation
targeting
microglial
promoting
clearance,
thereby
facilitating
post-SCI.
Bioactive Materials,
Год журнала:
2023,
Номер
32, С. 427 - 444
Опубликована: Окт. 27, 2023
Mitochondria
are
crucial
in
sustaining
and
orchestrating
cellular
functions.
Capitalizing
on
this,
we
explored
mitochondrial
transplantation
as
an
innovative
therapeutic
strategy
for
acute
spinal
cord
injury
(SCI).
In
our
study,
developed
engineered
compound
tailored
to
target
macrophages
within
the
SCI
region.
Sourced
from
IL-10-induced
Mertkhi
bone
marrow-derived
macrophages,
conjugated
a
peptide
sequence,
cations-cysteine-alanine-glutamine-lysine
(CAQK),
with
mitochondria,
optimizing
its
targeting
affinity
site.
Our
data
demonstrated
that
these
compounds
significantly
enhanced
macrophage
phagocytosis
of
myelin
debris,
curtailed
lipid
buildup,
ameliorated
dysfunction,
attenuated
pro-inflammatory
profiles
both
vitro
vivo.
The
intravenously
delivered
targeted
epicenter,
being
primary
recipients.
Critically,
they
promoted
tissue
regeneration
bolstered
functional
recovery
mice.
This
study
heralds
transformative
approach
SCI,
spotlighting
modulation
activity,
phagocytosis,
phenotype.
Biomedicines,
Год журнала:
2024,
Номер
12(3), С. 643 - 643
Опубликована: Март 13, 2024
Traumatic
injury
to
the
brain
and
spinal
cord
(neurotrauma)
is
a
common
event
across
populations
often
causes
profound
irreversible
disability.
Pathophysiological
responses
trauma
exacerbate
damage
of
an
index
injury,
propagating
loss
function
that
central
nervous
system
(CNS)
cannot
repair
after
initial
resolved.
The
way
in
which
lost
consequence
complex
array
mechanisms
continue
chronic
phase
post-injury
prevent
effective
neural
repair.
This
review
summarises
events
traumatic
(TBI)
(SCI),
comprising
description
current
clinical
management
strategies,
summary
known
cellular
molecular
secondary
their
role
prevention
A
discussion
emerging
approaches
promote
neuroregeneration
CNS
presented.
barriers
promoting
neurotrauma
are
pathways
cell
types
occur
on
level.
presents
challenge
traditional
pharmacological
targeting
single
pathways.
It
suggested
novel
multiple
or
using
combinatorial
therapies
may
yield
sought-after
recovery
for
future
patients.
Journal of Nanobiotechnology,
Год журнала:
2024,
Номер
22(1)
Опубликована: Июнь 20, 2024
Abstract
Spinal
cord
injury
(SCI)
often
results
in
motor
and
sensory
deficits,
or
even
paralysis.
Due
to
the
role
of
cascade
reaction,
effect
excessive
reactive
oxygen
species
(ROS)
early
middle
stages
SCI
severely
damage
neurons,
most
antioxidants
cannot
consistently
eliminate
ROS
at
non-toxic
doses,
which
leads
a
huge
compromise
antioxidant
treatment
SCI.
Selenium
nanoparticles
(SeNPs)
have
excellent
scavenging
bioactivity,
but
toxicity
control
problem
limits
therapeutic
window.
Here,
we
propose
synergistic
strategy
SeNPs
encapsulated
by
ZIF-8
(SeNPs@ZIF-8)
obtain
activity.
Three
different
spatial
structures
SeNPs@ZIF-8
were
synthesized
coated
with
ferrostatin-1,
ferroptosis
inhibitor
(FSZ
NPs),
achieve
enhanced
anti-oxidant
anti-ferroptosis
activity
without
toxicity.
FSZ
NPs
promoted
maintenance
mitochondrial
homeostasis,
thereby
regulating
expression
inflammatory
factors
promoting
polarization
macrophages
into
M2
phenotype.
In
addition,
presented
strong
abilities
promote
neuronal
maturation
axon
growth
through
activating
WNT4-dependent
pathways,
while
prevented
glial
scar
formation.
The
current
study
demonstrates
powerful
versatile
bioactive
functions
for
offers
inspiration
other
neural
diseases.
Cells,
Год журнала:
2022,
Номер
12(1), С. 120 - 120
Опубликована: Дек. 28, 2022
Spinal
Cord
Injury
(SCI)
is
a
common
neurological
disorder
with
devastating
psychical
and
psychosocial
sequelae.
The
majority
of
patients
after
SCI
suffer
from
permanent
disability
caused
by
motor
dysfunction,
impaired
sensation,
neuropathic
pain,
spasticity
as
well
urinary
complications,
small
number
experience
complete
recovery.
Current
standard
treatment
modalities
the
aim
to
prevent
secondary
injury
provide
limited
recovery
lost
functions.
Stem
Cell
Therapy
(SCT)
represents
an
emerging
approach
using
differentiation,
paracrine,
self-renewal
capabilities
stem
cells
regenerate
injured
spinal
cord.
To
date,
multipotent
including
mesenchymal
(MSCs),
neural
(NSCs),
hematopoietic
(HSCs)
represent
most
investigated
types
for
in
preclinical
clinical
studies.
microenvironment
has
significant
impact
on
survival,
proliferation,
differentiation
transplanted
cells.
Therefore,
deep
understanding
pathophysiology
molecular
mechanisms
through
which
act
may
help
improve
efficacy
SCT
find
new
therapeutic
approaches
such
stem-cell-derived
exosomes,
gene-modified
cells,
scaffolds,
nanomaterials.
In
this
literature
review,
pathogenesis
action
MSCs,
NSCs,
HSCs
are
comprehensively
described.
Moreover,
treatment,
optimal
protocol
cell
administration,
recent
based
or
combined
also
discussed.
Neural Regeneration Research,
Год журнала:
2023,
Номер
18(10), С. 2161 - 2161
Опубликована: Янв. 1, 2023
Traumatic
spinal
cord
injuries
interrupt
the
connection
of
all
axonal
projections
with
their
neuronal
targets
below
and
above
lesion
site.
This
interruption
results
in
either
temporary
or
permanent
alterations
locomotor,
sensory,
autonomic
functions.
Damage
tissue
prevents
re-growth
severed
axons
across
reconnection
targets.
Therefore,
absence
spontaneous
repair
leads
to
sustained
impairment
voluntary
control
movement
injury.
For
decades,
regeneration
have
been
considered
opitome
injury
goal
being
damaged
long
motor
sensory
tracts
a
complex
process
that
involves:
(1)
resealing
injured
axons;
(2)
reconstructing
cytoskeletal
structure
inside
(3)
re-establishing
healthy
growth
cones;
(4)
assembling
cargos.
These
biological
processes
require
an
efficient
production
adenosine
triphosphate,
which
is
affected
by
mitochondrial
dysfunction
after
From
pathological
standpoint,
during
secondary
stage
injury,
homeostasis
disrupted,
mainly
distal
segments
axons.
result
reduction
triphosphate
levels
subsequent
inactivation
triphosphate-dependent
ion
pumps
required
for
regulation
concentrations
reuptake
neurotransmitters,
such
as
glutamate.
The
consequences
are
calcium
overload,
reactive
oxygen
species
formation,
excitotoxicity.
events
intimately
related
activation
necrotic
apoptotic
cell
death
programs,
further
exacerbate
hallmark
why
restoring
function
early
could
represent
potentially
effective
therapeutic
intervention
overcome
failure
produced
review
discusses
most
recent
evidence
linking
context
It
also
covers
future
mitochondria-targeted
therapeutical
approaches,
antioxidant
molecules,
removing
anchor
proteins,
increasing
energetic
metabolism
through
creatine
treatment.
approaches
intended
enhance
functional
recovery
promoting
regeneration-reconnection
Expert Opinion on Therapeutic Targets,
Год журнала:
2023,
Номер
27(3), С. 171 - 187
Опубликована: Март 4, 2023
Introduction
Spinal
cord
injury
(SCI)
affects
25,000–50,000
people
around
the
world
each
year
and
there
is
no
cure
for
SCI
patients
currently.
The
primary
damages
spinal
tissues
secondary
mechanisms,
including
ischemia,
apoptosis,
inflammation,
astrogliosis,
further
exacerbate
lesions
to
cord.
Recently,
researchers
have
designed
various
therapeutic
approaches
by
targeting
its
major
cellular
or
molecular
pathophysiology.Areas
covered
Some
strategies
shown
promise
in
repairing
injured
functional
recoveries,
such
as
administering
neuroprotective
reagents,
specific
genes
promote
robust
axon
regeneration
of
disconnected
fiber
tracts,
epigenetic
factors
enhance
cell
survival
neural
repair,
facilitating
neuronal
relay
pathways
neuroplasticity
restoration
function
after
SCI.
This
review
focuses
on
advances
preclinical
therapies
reported
recent
years.Expert
opinion
Recent
progress
developing
novel
effective
encouraging,
but
many
challenges
remain
future
design
treatments,
highly
neuroprotectants
early
interventions,
stimulating
with
synaptic
reconnections
among
neurons,
maximizing
recovery
lost
functions
combination
strategies,
translating
most
promising
into
human
use.
ACS Biomaterials Science & Engineering,
Год журнала:
2023,
Номер
9(10), С. 5709 - 5723
Опубликована: Сен. 15, 2023
Spinal
cord
injury
is
an
impact-induced
disabling
condition.
A
series
of
pathological
changes
after
spinal
(SCI)
are
usually
associated
with
oxidative
stress,
inflammation,
and
apoptosis.
These
eventually
lead
to
paralysis.
The
short
half-life
low
bioavailability
many
drugs
also
limit
the
use
in
SCI.
In
this
study,
we
designed
nanovesicles
derived
from
macrophages
encapsulating
selenium
nanoparticles
(SeNPs)
metformin
(SeNPs-Met-MVs)
be
used
treatment
can
cross
blood–spinal
barrier
(BSCB)
deliver
SeNPs
Met
site
exert
anti-inflammatory
reactive
oxygen
species
scavenging
effects.
Transmission
electron
microscopy
(TEM)
images
showed
that
SeNPs-Met-MVs
particle
size
was
approximately
125
±
5
nm.
Drug
release
assays
exhibited
sustained
encapsulation
by
macrophage
cell
membrane.
cumulative
80%
over
36
h.
vitro
cellular
experiments
vivo
animal
demonstrated
decreased
(ROS)
malondialdehyde
(MDA)
levels,
increased
superoxide
dismutase
(SOD)
glutathione
peroxidase
(GSH-Px)
activities,
reduced
expression
inflammatory
(TNF-α,
IL-1β,
IL-6)
apoptotic
(cleaved
caspase-3)
cytokines
tissue
addition,
motor
function
mice
significantly
improved
treatment.
Therefore,
have
a
promising
future