The Journal of Experimental Medicine,
Journal Year:
2024,
Volume and Issue:
222(2)
Published: Dec. 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),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Dec. 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
The Journal of Experimental Medicine,
Journal Year:
2024,
Volume and Issue:
222(2)
Published: Dec. 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.
