bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 17, 2024
Abstract
The
vascular
system
regulates
brain
clearance
through
arterial
blood
flow
and
lymphatic
drainage
of
cerebrospinal
fluid
(CSF).
Idiopathic
intracranial
hypertension
(IIH),
characterized
by
elevated
pressure
dural
venous
sinus
stenoses,
can
be
treated
restoring
via
stenting,
suggesting
a
role
for
in
clearance.
Using
magnetic
resonance
imaging
(MRI)
IIH
patients
healthy
controls,
we
identified
that
stenoses
were
associated
with
impaired
drainage,
perivenous
retention,
accumulation.
To
investigate
this
further,
developed
mouse
model
bilateral
jugular
vein
ligation
(JVL),
which
recapitulated
key
human
findings,
including
hypertension,
calvarial
regression,
swelling
due
to
further
dissect
the
respective
roles
lymphatics
clearance,
performed
JVL
mice
depletion.
These
exhibited
spontaneous
pressure,
but
did
not
exacerbate
effect.
Moreover,
synchronous
restoration
observed
after
was
absent
lymphatic-deficient
mice.Transcriptomic
analyses
revealed
remodeling
induced
driven
VEGF-C
signaling
between
mesenchymal
endothelial
cells.
findings
establish
sinuses
as
critical
platform
where
interacts
cells
preserve
integrity
function,
essential
Frontiers in Aging Neuroscience,
Год журнала:
2025,
Номер
17
Опубликована: Апрель 11, 2025
Introduction
The
potential
for
therapeutic
strategies
that
promote
angiogenesis
and
suppress
neuroinflammation
to
ameliorate
cognitive
decline
induced
by
chronic
cerebral
hypoperfusion
(CCH)
has
led
their
recognition
as
promising
targets
vascular
dementia
(VD).
SIRT1-mediated
Notch1
signaling
pathway
is
important
in
regulating
neuroinflammation.
Previous
studies
have
demonstrated
baicalein
alleviates
rats
with
CCH.
Nevertheless,
it
remains
unclear
whether
can
stimulate
the
context
of
VD
this
protective
effect
achieved
pathway.
aim
study
was
investigate
impact
underlying
mechanism
on
Methods
Adult
Sprague-Dawley
(SD)
were
administered
or
a
SIRT1
inhibitor.
Cognitive
function
assessed
Morris
water
maze
(MWM)
test,
immunohistochemical
analysis
microvascular
density
(MVD)
number
CD31+/5-bromo-2’-deoxyuridine
(BrdU)+
cells.
Neuroinflammation
apoptosis
immunohistochemistry
GFAP,
Iba-1,
NEUN/cleaved
caspase-3,
ELISA
TNF-α
IL-1β.
Additionally,
Western
blotting
employed
evaluate
expression
Results
results
ameliorated
memory
learning
deficits
following
CCH
promoting
suppressing
However,
could
be
reversed
inhibiting
SIRT1.
Baicalein
observed
up-regulate
down-regulate
Notch1-related
molecules.
Discussion
SIRT1-related
plays
crucial
role
Moreover,
exerts
neuroprotective
against
through
pathway,
which
turn
improves
suppresses
Stroke,
encompassing
both
ischemic
and
hemorrhagic
subtypes,
is
a
leading
cause
of
mortality
disability
globally
current
treatments
remain
limited.
Neuroinflammation
plays
crucial
role
in
the
pathophysiology
stroke,
influencing
acute
injury
long-term
recovery.
This
review
aims
to
provide
comprehensive
overview
neuroinflammation
detailing
mechanisms,
clinical
implications,
potential
therapeutic
strategies.
A
detailed
literature
was
conducted,
focusing
on
recent
advancements
understanding
neuroinflammatory
processes
including
roles
thromboinflammation,
blood-brain
barrier
(BBB)
disruption,
immune
response.
The
initial
insult
triggers
an
inflammatory
cascade
involving
innate
adaptive
responses.
BBB
disruption
allows
peripheral
cells
neurotoxic
substances
infiltrate
brain,
exacerbating
neuronal
damage
increasing
risk
infections
such
as
pneumonia
urinary
tract
infections.
Thromboinflammation,
characterized
by
platelet
activation
cell
interactions,
further
complicates
environment.
Proteomic
studies
have
identified
key
biomarkers
that
offer
insights
into
mechanisms
targets.
Advances
imaging
techniques,
PET
MRI,
enable
real-time
monitoring
neuroinflammation,
facilitating
personalized
treatment
approaches.
significantly
impacts
stroke
outcomes,
presenting
challenges
opportunities
for
treatment.
Current
immunologic
strategies
are
Future
research
should
aim
elucidate
complex
interactions
refine
use,
develop
effective
interventions
mitigate
neuroinflammation.
Signal Transduction and Targeted Therapy,
Год журнала:
2025,
Номер
10(1)
Опубликована: Май 4, 2025
Abstract
In
recent
years,
increasing
evidence
has
suggested
that
meningeal
lymphatic
drainage
plays
a
significant
role
in
central
nervous
system
(CNS)
diseases.
Studies
have
indicated
CNS
diseases
and
conditions
associated
with
dysfunction
include
neurodegenerative
diseases,
stroke,
infections,
traumatic
brain
injury,
tumors,
functional
cranial
disorders,
hydrocephalus.
However,
the
understanding
of
regulatory
damage
mechanisms
lymphatics
under
physiological
pathological
is
currently
limited.
Given
importance
profound
interplay
between
this
review
covers
seven
key
aspects:
development
structure
vessels,
methods
for
observing
lymphatics,
function
molecular
relationships
vessels
potential
conclusions
outstanding
questions.
We
will
explore
relationship
development,
structure,
current
both
animal
models
humans,
identify
unresolved
points
research.
The
aim
to
provide
new
directions
future
research
therapeutic
strategies
targeting
by
critically
analyzing
advancements
field,
identifying
gaps
knowledge,
proposing
innovative
approaches
address
these
gaps.
Journal of Neuroinflammation,
Год журнала:
2025,
Номер
22(1)
Опубликована: Май 16, 2025
Meningeal
lymphatic
vessels
(mLVs)
play
a
critical
role
in
clearing
erythrocytes
from
the
subarachnoid
space
and
immune
cells
brain
parenchyma
following
hemorrhage
(SAH).
However,
drainage
function
of
mLVs
is
impaired
during
acute
stage
after
SAH
gradually
recovers
subacute
phase.
We
aimed
to
investigate
meningeal
transcriptional
response
post-SAH
elucidate
dynamic
influence
microenvironment
on
function.
employed
bioinformatics
analysis
single-cell
RNA
sequencing
spatial
transcriptomics
characterize
spatiotemporal
changes
early
post-SAH.
In
mouse
model
SAH,
potential
growth
factor
that
promoted
repair
were
further
investigated
validated.
During
phase,
myeloid
infiltrated
meninges
triggered
inflammatory
responses.
fibroblast
population
expanded
significantly,
contributing
tissue
remodeling.
The
interplay
between
fibroblasts
regulated
cell
migration
phenotypic
transition,
potentially
affecting
mLVs.
Notably,
placental
(PGF)
emerged
as
most
prominent
ligand
within
VEGF
signaling
pathway
received
by
endothelial
(mLECs)
This
event
was
associated
with
recovery
Our
study
revealed
transformation
an
"inflammatory
response"
phase
"tissue
remodeling"
SAH.
Monocyte-derived
macrophages
self-recruiting
neutrophils
contributed
impairment
stage,
while
PGF
might
serve
key
promoting
response.
These
findings
provided
novel
insights
into
cellular
dynamics
underlying
dysfunction
The Journal of Experimental Medicine,
Год журнала:
2024,
Номер
221(4)
Опубликована: Янв. 12, 2024
Meningeal
lymphatics
are
conduits
for
cerebrospinal
fluid
drainage
to
and
lymph
nodes
in
the
neck.
In
this
issue
of
JEM,
Boisserand
et
al.
(https://doi.org/10.1084/jem.20221983)
provide
evidence
that
expansion
meningeal
protects
against
ischemic
stroke.
The Journal of Experimental Medicine,
Год журнала:
2024,
Номер
222(2)
Опубликована: Дек. 24, 2024
Dysfunctional
lymphatic
drainage
from
the
central
nervous
system
(CNS)
has
been
linked
to
neuroinflammatory
and
neurodegenerative
disorders,
but
our
understanding
of
contribution
CNS
fluid
autoregulation
remains
limited.
Here,
we
studied
forces
that
drive
outflow
cerebrospinal
(CSF)
into
deep
superficial
cervical
lymph
nodes
(dcLN
scLN)
tested
how
blockade
networks
affects
homeostasis.
Outflow
dcLN
occurred
spontaneously
in
absence
pumping
was
coupled
intracranial
pressure
(ICP),
whereas
scLN
driven
by
pumping.
Impaired
led
elevated
CSF
resistance
delayed
CSF-to-blood
efflux
despite
recruitment
nasal-to-scLN
pathway.
Fluid
regulation
better
compensated
after
obstruction.
The
pathway
exhibited
steady,
consistent
across
conditions,
while
dynamically
activated
mitigate
perturbances.
These
findings
highlight
complex
physiology
homeostasis
lay
groundwork
for
future
studies
aimed
at
assessing
modulating
function.
Research Square (Research Square),
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 30, 2025
Abstract
The
vascular
system
regulates
brain
clearance
through
arterial
blood
flow
and
lymphatic
drainage
of
cerebrospinal
fluid
(CSF).
Idiopathic
intracranial
hypertension
(IIH),
characterized
by
elevated
pressure
dural
venous
sinus
stenoses,
can
be
treated
restoring
via
stenting,
suggesting
a
role
for
in
clearance.
Using
magnetic
resonance
imaging
(MRI)
IIH
patients
healthy
controls,
we
identified
that
stenoses
were
associated
with
impaired
drainage,
perivenous
retention,
accumulation.
To
investigate
this
further,
developed
mouse
model
bilateral
jugular
vein
ligation
(JVL),
which
recapitulated
key
human
findings,
including
hypertension,
calvarial
regression,
swelling
due
to
further
dissect
the
respective
roles
meningeal
vessels
clearance,
performed
JVL
mice
depletion.
These
exhibited
spontaneous
pressure,
but
did
not
exacerbate
effect.
Moreover,
synchronous
restoration
lymphatics
observed
after
was
absent
lymphatic-deficient
mice.Transcriptomic
analyses
revealed
remodeling
induced
driven
VEGF-C
signaling
between
mesenchymal
endothelial
cells.
findings
establish
sinuses
as
critical
platform
where
interacts
cells
preserve
integrity
function,
essential
