ABSTRACT
Background
Sepsis‐associated
encephalopathy
(SAE),
a
severe
neurological
disorder,
is
marked
by
widespread
brain
dysfunction.
At
present,
there
no
universally
accepted
criterion
for
diagnosing
SAE
in
animal
models.
This
study
proposes
standardized
evaluation
method
mice,
addressing
inconsistencies
current
research.
Method
Using
cecal
ligation
and
puncture
(CLP)
model
to
induce
sepsis,
we
assessed
the
physiological
status
of
mice
with
modified
SHIRPA
score
differentiate
from
non‐SAE,
validating
our
findings
through
various
behavioral
tests
evaluations
neuroinflammation
neuronal
damage.
Results
Our
revealed
that
conventional
mild–moderate–severe
categorization
was
insufficient
distinguishing
between
non‐SAE.
To
enhance
differentiation,
classified
based
on
median
score,
this
approach
including
Y‐maze,
three‐chamber
social
test,
open
field
test.
effectively
identified
impairments
septic
mice.
Further
validation
involved
assessing
damage,
neuroinflammation,
Morris
water
maze,
long‐term
potentiation
(LTP)
hippocampal
CA1
region.
indicated
up‐Median
group
exhibited
greater
injury,
cognitive
deficits
compared
down‐Median
group.
Conclusions
establishes
reliable
murine
models,
facilitating
improved
differentiation
Such
advancements
will
understanding
pathogenesis
guide
more
effective
treatment
strategies.
Journal of Inflammation Research,
Journal Year:
2025,
Volume and Issue:
Volume 18, P. 3843 - 3858
Published: March 1, 2025
Sepsis-associated
encephalopathy
(SAE)
critically
contributes
to
poor
prognosis
in
septic
patients.
Identifying
and
screening
key
genes
responsible
for
SAE,
as
well
exploring
potential
targeted
therapies,
are
vital
improving
the
management
of
sepsis
advancing
precision
medicine.
Single-cell
RNA
sequencing
(scRNA-seq)
was
administrated
identify
cell
subpopulations
related
Next,
hierarchical
dynamic
weighted
gene
co-expression
network
analysis
(hdWGCNA)
employed
associated
with
specific
neutrophil
subpopulations.
Enrichment
revealed
biological
functions
these
genes.
Subsequently,
neuroinflammation-related
were
obtained
construct
a
signature.
The
AddModuleScore
algorithm
used
calculate
neuroinflammation
scores
each
subpopulation,
whereas
CellCall
assess
crosstalk
between
neutrophils
other
To
accurately,
four
binary
classification
machine
learning
algorithms
utilized.
Finally,
Western
blotting
behavioral
tests
confirm
role
LCN2-related
mice.
This
study
utilized
scRNA-seq
reveal
critical
peripheral
during
sepsis,
identifying
contributors
neuroinflammation.
On
basis
various
algorithms,
we
discovered
that
Lipocalin-2
(LCN2)
may
be
involved
neutrophil-induced
SAE.
prove
findings,
conducted
vivo
experiments
an
animal
model.
Increased
LCN2
expression
cognitive
dysfunction
occurred
Additionally,
levels
markers
astrocytes
microglia
inflammatory
factors
such
TNF-α
IL-6
significantly
increased.
All
phenomena
reversed
by
downregulation
LCN2.
upregulation
on
is
step
triggers
central
nervous
system
ABSTRACT
Background
Sepsis‐associated
encephalopathy
(SAE),
a
severe
neurological
disorder,
is
marked
by
widespread
brain
dysfunction.
At
present,
there
no
universally
accepted
criterion
for
diagnosing
SAE
in
animal
models.
This
study
proposes
standardized
evaluation
method
mice,
addressing
inconsistencies
current
research.
Method
Using
cecal
ligation
and
puncture
(CLP)
model
to
induce
sepsis,
we
assessed
the
physiological
status
of
mice
with
modified
SHIRPA
score
differentiate
from
non‐SAE,
validating
our
findings
through
various
behavioral
tests
evaluations
neuroinflammation
neuronal
damage.
Results
Our
revealed
that
conventional
mild–moderate–severe
categorization
was
insufficient
distinguishing
between
non‐SAE.
To
enhance
differentiation,
classified
based
on
median
score,
this
approach
including
Y‐maze,
three‐chamber
social
test,
open
field
test.
effectively
identified
impairments
septic
mice.
Further
validation
involved
assessing
damage,
neuroinflammation,
Morris
water
maze,
long‐term
potentiation
(LTP)
hippocampal
CA1
region.
indicated
up‐Median
group
exhibited
greater
injury,
cognitive
deficits
compared
down‐Median
group.
Conclusions
establishes
reliable
murine
models,
facilitating
improved
differentiation
Such
advancements
will
understanding
pathogenesis
guide
more
effective
treatment
strategies.