Abstract
Osmotic
demyelination
syndrome
(ODS)
is
a
severe
neurological
complication
occuring
after
inadvertant
rapid
correction
of
chronic
hyponatremia.
This
pathology
primarily
affects
the
CNS
and
is
characterized
by
large
areas
of
demyelination
in
centropontine
or
extrapontine
regions,
often
correlated
with
neurological
symptoms
:
from
lethargia
to
coma
or
even
death.
Historically,
the
most
used
ODS
animal
model
is
Rattus
norvegicus,
that
mimicked
myelin
and
oligodendrocyte
loss
and
allowed
important
insights
in
the
management
and
in
the
understanding
of
ODS
pathology.
According
to
an
adapted
protocol
from
the
rat
model,
we
developed
a
murine
model
of
ODS
that
will
help
at
unravelling
the
molecular
and
cellular
pathophysiological
mechanisms.
Chronic
hyponatremia
was
induced
in
mice
using
continuous
desmopressin
infusion
and
a
low-‐sodium
liquid
diet.
After
4
days,
blood
sodium
dropped
to
112±7
mEq/L
in
the
hyponatremic
group
(compared
to
normonatremic
group
144±10
mEq/L,
p<0.001)
and
animals
showed
clinical
signs
of
mild
lethargia.
ODS
was
induced
by
the
correction
of
hyponatremia
using
a
single
injection
of
hypertonic
saline
targeting
a
normal
range
of
blood
sodium.
24
hours
after
correction,
blood
natremia
was
measured
to
determine
the
final
24-‐hours
sodium
correction
gradient
(37±7
mEq/L,
p<0.001
between
hyponatremia
and
correction
of
hyponatremia).
Interestingly,
mice
displayed
transient
increased
overall
locomotor
activity
during
the
first
12
hours
post-‐correction
before
a
drastic
worsening
of
neurological
symptoms,
most
likely
due
to
occurrence
of
demyelination.
Histopathologically,
ODS
mice
showed
large
areas
of
demyelination
in
subcortical
and
midbrain
regions,
attested
by
loss
of
myelin
in
Eriochrome
C
staining
and
anti-‐myelin
basic
protein
immunohistochemistry
starting
24
hours
after
the
correction.
As
early
as
24
hours
post-‐correction,
mice
showed
first
signs
of
myelin
vacuolization
in
midbrain
regions.
Intriguing
some
ODS
mice
showed
a
decreased
immunoreactivity
of
NeuN+
cells
in
thalamic
region.
The
number
of
APC+
oligodendrocytes
was
also
reduced
in
thalamus
and
cortex.
At
latter
time
points
(>96
hours
post-‐correction),
ODS-‐affected
brain
areas
(thalamus,
cortex)
showed
significant
astrogliosis,
as
assessed
by
GFAP
immunohistochemistry.
Using
an
anti-‐mouse
IgG
staining,
we
observed
plasmatic
IgG
leakage
in
the
ODS
brains
between
24
and
48
hours
post-‐correction,
suggesting
the
disruption
of
the
blood-‐brain
barrier.
In
conclusion,
we
successfully
translated
the
rat
model
of
ODS
to
a
mouse
model
and
reproduced
neurological
as
well
as
histological
outcomes
observed
in
human
cases
of
ODS.
Original language | English |
---|---|
Publication status | Published - 2015 |
Event | The Belgian Society for Cell and Developmental Biology Spring Meeting 2015 - Château de Colonster, Liège, Belgium Duration: 6 Jun 2015 → 6 Jun 2015 |
Meeting
Meeting | The Belgian Society for Cell and Developmental Biology Spring Meeting 2015 |
---|---|
Country/Territory | Belgium |
City | Liège |
Period | 6/06/15 → 6/06/15 |