Research Square (Research Square),
Год журнала:
2025,
Номер
unknown
Опубликована: Март 25, 2025
Abstract
The
hypothalamus
is
critical
for
regulating
behaviors
essential
survival
and
locomotion,
but
how
it
integrates
internal
needs
transmits
locomotion
commands
to
the
spinal
cord
(SC)
remains
unclear.
We
found
that
glutamatergic
neurons
in
lateral
hypothalamic
area
(LHA)
are
motivated
locomotor
activity.
Using
single-neuron
projectome
analysis,
trans-synaptic
tracing,
optogenetic
manipulation,
we
showed
LHA
facilitates
during
food
seeking
via
pontine
oral
part
(PnO)
projection
neurons,
rather
than
direct
SC
projections
or
indirect
stress
signaling
medial
septum
diagonal
band.
Activating
PnO-SC
also
initiated
locomotion.
Importantly,
LHA-PnO
were
crucial
recovery
following
mouse
injury
(SCI).
Motor
cortex
signals
gated
deep
brain
stimulation
treatment
markedly
promoted
long-term
restoration
of
hindlimb
motor
functions
after
severe
SCI.
Thus,
have
identified
a
hypothalamic-pontine-spinal
pathway
paradigm
potential
therapeutic
intervention
Biomedical Materials,
Год журнала:
2024,
Номер
19(3), С. 032005 - 032005
Опубликована: Апрель 18, 2024
Spinal
cord
injury
(SCI)
is
a
devastating
neurological
disorder,
leading
to
loss
of
motor
or
somatosensory
function,
which
the
most
challenging
worldwide
medical
problem.
Re-establishment
intact
neural
circuits
basis
spinal
regeneration.
Considering
crucial
role
electrical
signals
in
nervous
system,
electroactive
bioscaffolds
have
been
widely
developed
for
SCI
repair.
They
can
produce
conductive
pathways
and
pro-regenerative
microenvironment
at
lesion
site
similar
that
natural
cord,
neuronal
regeneration
axonal
growth,
functionally
reactivating
damaged
circuits.
In
this
review,
we
first
demonstrate
pathophysiological
characteristics
induced
by
SCI.
Then,
repair
introduced.
Based
on
comprehensive
analysis
these
characteristics,
recent
advances
are
summarized,
focusing
both
piezoelectric
bioscaffolds,
used
independently
combination
with
external
electronic
stimulation.
Finally,
thoughts
challenges
opportunities
may
shape
future
concluded.
Advanced Science,
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 18, 2024
Abstract
Spinal
cord
injury
(SCI)
is
a
severe
to
the
central
nervous
system,
and
its
treatment
always
major
medical
challenge.
Proinflammatory
cell
death
considered
an
important
factor
affecting
neuroinflammation
prognosis
after
injury.
PANoptosis,
newly
discovered
type
of
proinflammatory
death,
regulates
activation
executioner
molecules
apoptosis,
pyroptosis
necroptosis
through
PANoptosome,
providing
new
target
for
therapeutic
intervention
SCI.
However,
role
regulatory
mechanism
in
SCI
are
not
yet
elucidated.
Here,
based
on
proteomic
data,
YBX1
expression
significantly
increased
neurons
Guided
by
RIP‐seq,
subsequent
experiments
reveal
that
promotes
ZBP1
stabilizing
Zbp1
mRNA,
thereby
aggravating
ZBP1‐mediated
PANoptosis.
Furthermore,
E3
ubiquitin
ligase
TRIM56
identified
as
endogenous
inhibitor
via
molecular
docking
IP/MS
analysis.
Mechanistically,
bound
promoted
ubiquitination,
accelerating
degradation.
Taken
together,
these
findings
novel
function
regulating
PANoptosis
pathogenesis
verified
functions
promote
ubiquitin‐proteasomal
degradation
YBX1,
insights
into
strategies.
Spinal
cord
injury
(SCI)
remains
a
formidable
challenge
in
biomedical
research,
as
the
silencing
of
intrinsic
regenerative
signals
most
spinal
neurons
results
an
inability
to
reestablish
neural
circuits.
In
this
study,
we
found
that
with
low
axonal
regeneration
after
SCI
showed
decreased
extracellular
signal-regulated
kinase
(ERK)
phosphorylation
levels.
However,
expression
dual
specificity
phosphatase
26
(DUSP26)─which
negatively
regulates
ERK
phosphorylation─was
reduced
considerably
undergoing
spontaneous
regeneration.
Therefore,
developed
system
named
F10@MS@UV-HG
integrated
DUSP26-specific
inhibitor
into
reactive
oxygen
species-responsive
nanoparticles
and
embedded
them
photosensitive
hydrogels.
This
effectively
downregulated
DUSP26
primary
enhanced
phosphorylation,
ultimately
promoting
outgrowth.
When
transplanted
mouse
model,
achieved
sustained
drug
release,
specifically
targeting
DUSP26/ERK/ELK1
pathway
facilitating
short-term
Additionally,
long-term
repair
effects─including
improved
myelination
motor
function─were
evident
mice
F10@MS@UV-HG.
The
suggested
activating
signaling
by
modulating
could
promote
functional
recovery.
Thus,
exhibits
enormous
potential
therapeutic
approach
for
patients
SCI.
Journal of Translational Medicine,
Год журнала:
2025,
Номер
23(1)
Опубликована: Фев. 20, 2025
spinal
cord
injury
(SCI)
disrupts
the
gut
microbiota,
worsening
injury's
impact.
Fecal
microbiota
transplantation
(FMT)
is
increasingly
recognized
as
a
promising
strategy
to
improve
neural
function
post-SCI,
yet
its
precise
mechanisms
are
still
far
from
clear.
The
present
study
aims
elucidate
how
FMT
influences
motor
recovery
and
underlying
utilizing
SCI
mouse
model.
Mice
with
received
healthy
donors.
We
used
16
S
rRNA
amplicon
sequencing
analyze
alterations
of
microbes.
Pathological
in
tissue,
including
neuronal
survival,
axonal
regeneration,
cell
proliferation,
neuroinflammation,
were
assessed
among
experimental
groups.
Additionally,
RNA
(RNA-seq)
was
explore
relevant
signaling
pathways.
Significant
shifts
composition
following
observed
through
analysis.
On
day
7
group
exhibited
significantly
higher
diversity
compared
ABX
group,
more
closely
resembling
that
mice.
promoted
survival
leading
notable
improvements
control
Immunofluorescence
staining
showed
increased
alleviated
extracellular
matrix
(ECM)
deposition,
diminished
glial
scar
formation,
reduced
inflammation
FMT-treated
RNA-seq
analysis
indicated
induced
transcriptomic
changes
associated
material
metabolism,
ECM
remodeling,
anti-inflammatory
responses.
restored
balance
mice,
mitigated
inflammation,
establishing
an
optimal
environment
for
recovery.
These
findings
demonstrated
may
represent
valuable
approach
enhance
functional
SCI.
Materials Today Bio,
Год журнала:
2025,
Номер
32, С. 101639 - 101639
Опубликована: Март 4, 2025
Motor
function
recovery
after
complete
spinal
cord
injury
remained
as
a
challenge
in
medical
field,
while
one
of
the
key
approaches
is
promoting
local
microenvironments.
In
this
research,
we
performed
conjugated
therapy
by
transplantation
neural
stem
cell
(NSC)
scaffolds
and
umbilical
mesenchymal
derived
exosomes
(ucMSC-exos)
for
treatment
transactional
(SCI).
We
first
demonstrated
anti-inflammatory
effects
ucMSC-exos
vitro
found
that
could
regulate
microglia
polarization
from
M1
to
M2,
an
phenotype.
Besides,
also
promoted
NSC
proliferation
differentiation
during
culturing.
On
other
hand,
core-shell
hydrogel
microfibers
were
used
both
small
large
SCI
defects.
The
carry
amounts
NSCs
core
portion
shell
highly
permeable
nutrient
metabolite
transportation.
vivo
experiments,
decreased
inflammatory
cytokines
at
lesion
sites,
gave
rise
more
neurons
angiogenesis,
thus
comprehensively
improved
microenvironment
compared
with
only.
These
beneficial
results
accordance
those
experiments
further
led
better
locomotor
recovery.
summary,
research
has
make
potential
tool
repair.
Nature Communications,
Год журнала:
2025,
Номер
16(1)
Опубликована: Март 4, 2025
Mechanisms
underlying
functional
axonal
rewiring
after
adult
mammalian
central
nervous
system
(CNS)
injuries
remain
unclear
partially
due
to
limited
models.
Here
we
develop
a
mouse
intracranial
pre-olivary
pretectal
nucleus
(OPN)
optic
tract
injury
model
and
demonstrate
that
Pten/Socs3
knockout
CNTF
expression
in
retinal
ganglion
cells
(RGCs)
promotes
regeneration
OPN
reinnervation.
Revealed
by
transmission
electron
microscopy,
trans-synaptic
labeling,
electrophysiology,
synapses
are
formed
mainly
intrinsically
photosensitive
RGCs,
thereby
restoring
the
pupillary
light
reflex
(PLR).
Moreover,
combining
with
Lipin1
knockdown
accelerates
recovery
achieves
reconnection
chronic
injury.
PLR
can
be
further
boosted
increasing
RGC
photosensitivity
melanopsin
overexpression,
it
also
enhanced
treatment
of
voltage-gated
calcium
channel
modulator
augment
presynaptic
release.
These
findings
highlight
importance
neuronal
types
activity
for
CNS
injuries.
