Deciphering Consciousness: The Role of Corticothalamocortical Interactions in General Anesthesia
Pharmacological Research,
Год журнала:
2025,
Номер
212, С. 107593 - 107593
Опубликована: Янв. 8, 2025
General
anesthesia
is
administered
to
millions
of
individuals
each
year,
however,
the
precise
mechanism
by
which
it
induces
unconsciousness
remains
unclear.
While
some
theories
suggest
that
shares
similarities
with
natural
sleep,
targeting
sleep-promoting
areas
and
inhibiting
arousal
nuclei,
recent
research
indicates
a
more
complex
process.
Emerging
evidence
highlights
critical
role
corticothalamocortical
circuits,
are
involved
in
higher
cognitive
functions,
controlling
states
modulating
transitions
between
different
conscious
during
anesthesia.
The
administration
general
anesthetics
disrupts
connectivity
within
these
resulting
reversible
state
unconsciousness.
This
review
elucidates
how
impair
interactions,
thereby
affecting
flow
information
across
various
cortical
layers
disrupting
higher-order
functions
while
preserving
basic
sensory
processing.
Additionally,
prefrontal
cortex
regulating
through
both
top-down
bottom-up
pathways
was
examined.
These
findings
highlight
intricate
interplay
subcortical
networks
maintaining
restoring
consciousness
under
anesthesia,
offering
potential
therapeutic
targets
for
enhancing
management.
Язык: Английский
Proteomic Learning of Gamma-Aminobutyric Acid (GABA) Receptor-Mediated Anesthesia
Journal of Chemical Information and Modeling,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 17, 2025
Anesthetics
are
crucial
in
surgical
procedures
and
therapeutic
interventions,
but
they
come
with
side
effects
varying
levels
of
effectiveness,
calling
for
novel
anesthetic
agents
that
offer
more
precise
controllable
effects.
Targeting
Gamma-aminobutyric
acid
(GABA)
receptors,
the
primary
inhibitory
receptors
central
nervous
system,
could
enhance
their
action,
potentially
reducing
while
improving
potency
anesthetics.
In
this
study,
we
introduce
a
proteomic
learning
GABA
receptor-mediated
anesthesia
based
on
24
receptor
subtypes
by
considering
over
4000
proteins
protein-protein
interaction
(PPI)
networks
1.5
millions
known
binding
compounds.
We
develop
corresponding
drug-target
network
to
identify
potential
lead
compounds
design.
To
ensure
robust
predictions,
curated
dataset
comprising
136
targets
from
pool
980
within
PPI
networks.
employed
three
machine
algorithms,
integrating
advanced
natural
language
processing
(NLP)
models
such
as
pretrained
transformer
autoencoder
embeddings.
Through
comprehensive
screening
process,
evaluated
repurposing
180,000
drug
candidates
targeting
GABRA5
receptor.
Additionally,
assessed
ADMET
(absorption,
distribution,
metabolism,
excretion,
toxicity)
properties
these
those
near-optimal
characteristics.
This
approach
also
involved
optimizing
structures
existing
Our
work
presents
an
innovative
strategy
development
new
drugs,
optimization
use,
deeper
understanding
anesthesia-related
Язык: Английский
Centralising a loss of consciousness to the central medial thalamus
Brain and Neuroscience Advances,
Год журнала:
2024,
Номер
8
Опубликована: Янв. 1, 2024
Although
a
role
of
the
thalamus
in
different
arousal
and
awareness
states
is
well
established,
there
surprising
lack
knowledge
on
subregional
specificity
within
this
complex,
multinucleated
structure
diencephalon.
In
their
recent
paper
‘Extrasynaptic
GABA-A
receptors
central
medial
mediate
anaesthesia
rats’,
Muheyati
et
al.
evaluated
whether
GABA
A
expressed
(CM),
paraventricular
(PV)
or
lateral
mediodorsal
(MD)
nuclei
contribute
to
loss
righting
reflex
(LORR)
rats.
Deficits
have
previously
been
interpreted
as
surrogate
marker
altered
levels
consciousness.
Using
range
convergent
techniques,
authors
report
novel
finding
that
delta
subunit-expressing
CM
distinct
states.
This
important
discovery
implicates
tonic
-mediated
conductance
may
be
relevant
for
minimally
conscious
other
conditions
awareness.
Язык: Английский