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
Nature Cardiovascular Research,
Год журнала:
2024,
Номер
3(4), С. 474 - 491
Опубликована: Март 15, 2024
Abstract
Discovery
of
meningeal
lymphatic
vessels
(LVs)
in
the
dura
mater,
also
known
as
dural
LVs
(dLVs)
that
depend
on
vascular
endothelial
growth
factor
C
expression,
has
raised
interest
their
possible
involvement
Alzheimer’s
disease
(AD).
Here
we
find
APdE9
and
5xFAD
mouse
models
AD,
amyloid-β
(Aβ)
is
confined
to
blood
dLV
morphology
or
function
not
altered.
The
induction
sustained
atrophy
hyperplasia
AD
mice
by
blocking
overexpressing
C,
impaired
improved,
respectively,
macromolecular
cerebrospinal
fluid
(CSF)
drainage
cervical
lymph
nodes.
Yet,
manipulation
dLVs
did
significantly
alter
overall
brain
Aβ
plaque
load.
Moreover,
behavioral
phenotypes
mice,
but
it
improved
CSF-to-blood
drainage.
Our
results
indicate
does
affect
deposition
compensatory
mechanisms
promote
CSF
clearance.
iScience,
Год журнала:
2025,
Номер
28(2), С. 111705 - 111705
Опубликована: Янв. 5, 2025
Biomedicine
has
seen
significant
advancements
in
the
21st
century,
with
platelet-rich
plasma
(PRP)
playing
a
crucial
role
clinical
practice.
This
blood
derivative,
enriched
platelet
components,
shown
great
potential
for
promoting
tissue
repair
and
regeneration.
Its
wide
range
of
applications
presence
anti-inflammatory
growth-promoting
factors
make
it
valuable
tool
field
biomedicine.
The
exploration
PRP
settings
been
gaining
momentum.
Despite
its
cost-effectiveness,
safety,
therapeutic
efficacy,
widespread
adoption
hindered
by
absence
consistent
preparation
standards
standardized
treatment
protocols.
article
provides
comprehensive
analysis
uses,
physiological
roles,
molecular
mechanisms,
techniques
aim
is
to
offer
thorough
understanding
benefits
medical
Translational Stroke Research,
Год журнала:
2024,
Номер
unknown
Опубликована: Июнь 1, 2024
Timely
relief
of
edema
and
clearance
waste
products,
as
well
promotion
anti-inflammatory
immune
responses,
reduce
ischemic
stroke
pathology,
attenuate
harmful
long-term
effects
post-stroke.
The
discovery
an
extensive
functional
lymphatic
vessel
system
in
the
outermost
meningeal
layer,
dura
mater,
has
opened
up
new
possibilities
to
facilitate
post-stroke
recovery
by
inducing
dural
(dLV)
growth
via
a
single
injection
vector
encoding
vascular
endothelial
factor
C
(VEGF-C).
In
present
study,
we
aimed
improve
outcomes
dLV
mice.
We
injected
mice
with
intracerebroventricular
dose
adeno-associated
viral
particles
VEGF-C
before
subjecting
them
transient
middle
cerebral
artery
occlusion
(tMCAo).
Behavioral
testing,
Gadolinium
(Gd)
contrast
agent-enhanced
magnetic
resonance
imaging
(MRI),
immunohistochemical
analysis
were
performed
define
impact
on
outcome.
improved
stroke-induced
behavioral
deficits,
such
gait
disturbances
neurological
ameliorated
inflammation,
enhanced
alternative
glial
response.
Importantly,
treatment
increased
drainage
brain
interstitial
fluid
(ISF)
cerebrospinal
(CSF),
shown
Gd-enhanced
MRI.
These
closely
associated
increase
dLVs
around
region
where
observed
vefgc
mRNA
expression
within
brain,
including
olfactory
bulb,
cortex,
cerebellum.
Strikingly,
VEGF-C-treated
exhibited
faster
stronger
Gd-signal
accumulation
core
area
outflow
cribriform
plate.
conclusion,
VEGF-C-induced
overall
outcome
post-stroke,
indicating
that
potential
be
included
strategies
post-ischemic
stroke.
However,
maximize
therapeutic
treatment,
further
studies
at
clinically
relevant
time
points
are
essential.
Journal of Cerebral Blood Flow & Metabolism,
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 9, 2024
Single-cell
RNA
sequencing
(scRNA-seq)
is
a
high-throughput
transcriptomic
approach
with
the
power
to
identify
rare
cells,
discover
new
cellular
subclusters,
and
describe
novel
genes.
scRNA-seq
can
simultaneously
reveal
dynamic
shifts
in
phenotypes
heterogeneities
subtypes.
Since
publication
of
first
protocol
on
2009,
this
evolving
technology
has
continued
improve,
through
use
cell-specific
barcodes,
adoption
droplet-based
systems,
development
advanced
computational
methods.
Despite
induction
stress
response
during
tissue
dissociation
process,
remains
popular
technology,
commercially
available
methods
have
been
applied
brain.
Recent
advances
spatial
transcriptomics
now
allow
researcher
capture
positional
context
transcriptional
activity,
strengthening
our
knowledge
organization
cell-cell
interactions
spatially
intact
tissues.
A
combination
data
proteomic,
metabolomic,
or
chromatin
accessibility
promising
direction
for
future
research.
Herein,
we
provide
an
overview
workflow,
analyses
methods,
pros
cons
technology.
We
also
summarize
latest
achievements
stroke
acute
traumatic
brain
injury,
applications
transcriptomics.
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.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 14, 2025
Abstract
The
liver
lymphatic
system
plays
a
critical
role
in
maintaining
interstitial
fluid
balance
and
immune
regulation.
Efficient
drainage
is
essential
for
homeostasis,
but
its
disease
progression
remains
poorly
understood.
In
cirrhosis,
lymphangiogenesis
initially
compensates
increased
lymph
production,
impaired
advanced
stages
may
lead
to
complications
such
as
ascites
portal
hypertension.
This
study
aimed
evaluate
how
dysfunction
affects
assess
therapeutic
strategies.
Using
surgical
model
block
outflow,
we
found
that
accelerates
injury,
fibrosis,
cell
infiltration,
even
healthy
livers.
Mechanistically,
enhanced
TGF-β
signaling
endothelial
cells
(LyECs)
contributed
reduced
vessel
(LV)
density
function
late-stage
decompensated
cirrhosis.
was
linked
the
from
compensated
particularly
patients
with
primary
sclerosing
cholangitis
(PSC).
Conversely,
liver-specific
overexpression
of
VEGF-C
via
AAV8
improved
drainage,
restored
LV
density,
mitigated
alleviated
hypertension
cirrhotic
rats.
These
findings
establish
pivotal
driver
cirrhosis
identify
promising
target
prevent
decompensation.
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
Biologics,
Год журнала:
2025,
Номер
5(1), С. 7 - 7
Опубликована: Март 3, 2025
The
molecular
regulation
and
therapeutic
applications
of
brain-derived
neurotrophic
factor
(BDNF)–tropomyosin-related
kinase
B
(TrkB)
signaling
in
major
depressive
disorder
(MDD)
through
interaction
with
vascular
endothelial
growth
(VEGF)
N-methyl-D-aspartic
acid
(NMDA)
receptors
show
promise.
While
BDNF-TrkB
is
implicated
antidepressant
action,
the
association
between
BDNFs
depression
has
not
yielded
conclusive
results.
Some
studies
decreased
BDNF
levels
depression,
while
others
indicate
that
increased
expression
certain
brain
regions
can
induce
susceptibility.
role
varies
across
different
regions,
necessitating
further
study
individual
mechanisms.
This
regional
variability
complicates
development
targeted
therapies.
antidepressant-like
actions
require
VEGF
signaling,
but
there
also
a
reciprocal
interdependence,
as
are
dependent
on
BDNFs.
complex
relationship
Journal of Biomedical Science,
Год журнала:
2025,
Номер
32(1)
Опубликована: Март 6, 2025
Neurons
rely
on
the
bloodstream
for
essential
nutrients
and
oxygen,
which
is
facilitated
by
an
intricate
coupling
of
neuronal
vascular
systems.
Central
to
this
neurovascular
interaction
endothelial
growth
factor
(VEGF)
family,
a
group
secreted
factors
traditionally
known
their
roles
in
promoting
cell
proliferation,
migration,
survival
cardiovascular
lymphatic
However,
emerging
evidence
shows
that
VEGFs
also
play
indispensable
nervous
system,
extending
beyond
canonical
angiogenic
lymphangiogenic
functions.
Over
past
two
decades,
have
been
found
exert
direct
effects
neurons,
influencing
key
aspects
function
independently
actions
cells.
In
particular,
it
has
become
increasingly
evident
crucial
functions
development,
regulation,
maintenance
morphology.
Understanding
development
high
scientific
clinical
interest
because
significance
precise
morphology
neural
connectivity
network
function,
as
well
association
morphological
abnormalities
with
neurological
neurodegenerative
disorders.
This
review
begins
overview
VEGF
family
members,
structural
characteristics,
receptors,
established
vasculature.
then
highlights
focuses
exciting
variety
VEGFs,
especially
role
