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
Cells,
Год журнала:
2024,
Номер
13(21), С. 1815 - 1815
Опубликована: Ноя. 4, 2024
Many
types
of
viruses
directly
or
indirectly
target
the
vascular
endothelial
growth
factor
(VEGF)
system,
which
is
a
central
regulator
vasculogenesis
and
angiogenesis
in
physiological
homeostasis,
causing
diverse
pathologies.
Other
have
been
developed
into
effective
therapeutic
tools
for
VEGF
modulation
conditions
such
as
cancer
eye
diseases.
Some
may
alter
levels
pathogenesis
respiratory
syndromes,
they
encode
VEGF-like
factors,
promoting
disruption
to
enable
viruses’
systemic
spread.
Oncogenic
express
interactive
factors
that
perturb
VEGF’s
functional
downstream
signaling,
increases
neovascularization
metastasis
tumors.
Furthermore,
many
are
being
vectors
pathologies
clinical
trials.
Major
examples
those
viral
inhibit
role
required
progression;
this
achieved
through
induction
immune
responses,
by
exposing
specific
peptides
block
signaling
expressing
anti-VEGF
receptor-neutralizing
antibodies.
engineered
pro-
anti-angiogenesis
multitarget
neovascular
diseases,
paving
way
therapies
with
improved
safety
minimal
side
effects.
This
article
critically
reviews
large
body
literature
on
these
issues,
highlighting
contributions
describe
molecular
mechanisms,
thus
expanding
our
understanding
VEGF–virus
interactions
disease
therapy.
could
facilitate
use
virus
precision
medicine
system.
Frontiers in Cell and Developmental Biology,
Год журнала:
2024,
Номер
12
Опубликована: Сен. 6, 2024
The
brain
has
traditionally
been
considered
an
"immune-privileged"
organ
lacking
a
lymphatic
system.
However,
recent
studies
have
challenged
this
view
by
identifying
the
presence
of
glymphatic
system
and
meningeal
vessels
(MLVs).
These
discoveries
offer
new
opportunities
for
waste
clearance
treatment
central
nervous
(CNS)
diseases.
Various
strategies
developed
based
on
these
pathways,
including
modulation
function,
enhancement
drainage,
utilization
routes
drug
delivery.
Consequently,
review
explores
developmental
features
physiological
roles
cerebral
as
well
its
significance
in
various
CNS
disorders.
Notably,
ameliorating
diseases
discussed
with
focus
enhancing
MLVs
functionality
through
factors
along
implementing
pharmacological
physical
treatments.
Additionally,
emphasis
is
placed
potential
use
delivery
while
envisioning
future
directions
terms
mechanisms,
applications,
translational
research.
The Journal of Experimental Medicine,
Год журнала:
2024,
Номер
222(2)
Опубликована: Дек. 12, 2024
Cerebrospinal
fluid
(CSF),
antigens,
and
antigen-presenting
cells
drain
from
the
central
nervous
system
(CNS)
into
lymphatic
vessels
near
cribriform
plate
dura,
yet
role
of
these
during
stroke
is
unclear.
Using
a
mouse
model
ischemic
stroke,
transient
middle
cerebral
artery
occlusion
(tMCAO),
we
demonstrate
stroke-induced
lymphangiogenesis
plate,
peaking
at
day
7
regressing
by
14.
Lymphangiogenesis
restricted
to
deep
cervical
lymph
nodes
regulated
VEGF-C/VEGFR-3
signaling.
The
use
VEGFR-3
inhibitor
prevented
led
improved
outcomes
earlier
time
points,
with
no
effects
later
points.
VEGF-C
delivery
after
tMCAO
did
not
further
increase
post-stroke
lymphangiogenesis,
but
instead
induced
larger
brain
infarcts.
Our
data
support
damaging
acutely
pro-angiogenic
chronically.
This
nuanced
understanding
in
pathology
advises
caution
regarding
therapeutic
stroke.
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
