International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(10), С. 4704 - 4704
Опубликована: Май 14, 2025
Progression
independent
of
relapse
activity
(PIRA)
is
increasingly
recognized
as
a
key
driver
disability
in
multiple
sclerosis
(MS).
However,
the
concept
PIRA
remains
elusive,
with
uncertainty
surrounding
its
definition,
underlying
mechanisms,
and
methods
quantification.
This
review
examines
current
landscape
biomarkers
used
to
predict
measure
PIRA,
focusing
on
clinical,
imaging,
body
fluid
biomarkers.
Clinical
scores
such
Expanded
Disability
Status
Scale
(EDSS)
are
widely
used,
but
may
lack
sensitivity
capturing
subtle
relapse-independent
progression.
Imaging
biomarkers,
including
MRI-derived
metrics
(brain
spinal
cord
volume
loss,
chronic
active
lesions)
optical
coherence
tomography
(OCT)
parameters
(retinal
nerve
fiber
layer
ganglion
cell-inner
plexiform
thinning),
offer
valuable
insights,
often
reflect
both
inflammatory
neurodegenerative
processes.
Body
neurofilament
light
chain
(NfL)
glial
fibrillary
acidic
protein
(GFAP),
promising
indicators
axonal
damage
activation,
their
specificity
for
limited.
emphasizes
distinction
between
predicting
PIRA-identifying
individuals
at
risk
future
progression-and
measuring
ongoing
PIRA-related
real
time.
We
highlight
limitations
differentiating
from
relapse-associated
call
clearer
conceptual
framework
guide
research.
Advancing
precision
utility
will
require
multimodal
approaches,
longitudinal
studies,
standardized
protocols
enable
clinical
integration
improve
personalized
MS
management.
Brain,
Год журнала:
2022,
Номер
146(4), С. 1243 - 1266
Опубликована: Ноя. 18, 2022
Myelin
is
the
protective
sheath
wrapped
around
axons,
consisting
of
a
phospholipid
bilayer
with
water
between
wraps.
The
measurement
damage
to
myelin
sheaths,
evaluation
efficacy
therapies
aiming
promote
remyelination
and
monitoring
degree
brain
maturation
in
children
all
require
non-invasive
quantitative
imaging
methods.
To
date,
various
techniques
have
been
developed.
Five
different
MRI
approaches
can
be
distinguished
based
on
their
biophysical
principles:
(i)
lipid
bilayers
directly
(e.g.
imaging);
(ii)
non-aqueous
protons
ultra-short
echo-time
techniques;
(iii)
indirect
macromolecular
content
magnetization
transfer;
inhomogeneous
transfer);
(iv)
mapping
effects
sheath's
magnetic
susceptibility
signal
mapping);
(v)
diffusion.
PET
uses
radioactive
molecules
high
affinity
specific
components,
particular
basic
protein.
This
review
aims
give
an
overview
techniques,
principles,
image
acquisition,
data
analysis
validation
status.
Current Opinion in Neurology,
Год журнала:
2022,
Номер
35(3), С. 299 - 306
Опубликована: Июнь 1, 2022
Purpose
of
review
Microglia
normally
protects
the
central
nervous
system
(CNS)
against
insults.
However,
their
persistent
activation
in
multiple
sclerosis
(MS)
contributes
to
injury.
Here,
we
microglia
MS
and
detection
using
positron
emission
tomography
(PET).
Recent
findings
During
lesion
evolution
progression
MS,
activity
may
contribute
neurotoxicity
through
release
pro-inflammatory
cytokines,
reactive
oxidative
species,
proteases
glutamate.
A
means
detect
monitor
individuals
living
with
is
provided
by
(PET)
imaging
mitochondrial
18-kDa
translocator
protein
(TSPO)
ligand.
TSPO
PET
shows
increased
microglial
within
normal
appearing
white
matter
that
precedes
radiological
signs
neurodegeneration
measured
T2
enlargement.
PET-detected
increases
MS.
These
demand
use
CNS
penetrant
inhibitors
affect
microglia.
Such
therapies
include
hydroxychloroquine
recently
reported
a
small
study
reduce
expected
primary
progressive
Bruton's
tyrosine
kinase
for
which
there
are
now
eleven
Phase
3
registered
trials
Summary
Microglial
drives
injury
microglia-specific
ligands
offer
new
insights
into
as
treatment
responses.
Angewandte Chemie International Edition,
Год журнала:
2024,
Номер
63(36)
Опубликована: Июнь 20, 2024
Developing
real-time,
dynamic,
and
in
situ
analytical
methods
with
high
spatial
temporal
resolutions
is
crucial
for
exploring
biochemical
processes
the
brain.
Although
vivo
electrochemical
based
on
carbon
fiber
(CF)
microelectrodes
are
effective
monitoring
neurochemical
dynamics
during
physiological
pathological
processes,
complex
post
modification
hinders
large-scale
productions
widespread
neuroscience
applications.
Herein,
we
develop
a
general
strategy
engineering
of
carbon-based
materials
to
mass-produce
functional
CFs
by
introducing
polydopamine
anchor
zeolitic
imidazolate
frameworks
as
precursors,
followed
one-step
pyrolysis.
This
demonstrates
exceptional
universality
design
flexibility,
overcoming
post-modification
procedures
avoiding
delamination
layer.
simplifies
fabrication
integration
CF-based
microelectrodes.
Moreover,
highly
stable
selective
H
Science Translational Medicine,
Год журнала:
2025,
Номер
17(780)
Опубликована: Янв. 8, 2025
In
multiple
sclerosis
(MS),
microglia
and
macrophages
within
the
central
nervous
system
(CNS)
play
an
important
role
in
determining
balance
among
demyelination,
neurodegeneration,
myelin
repair.
Phagocytic
regenerative
functions
of
these
CNS
innate
immune
cells
support
remyelination,
whereas
chronic
maladaptive
inflammatory
activation
promotes
lesion
expansion
disability,
particularly
progressive
forms
MS.
No
currently
approved
drugs
convincingly
target
CNS,
contributing
to
lack
therapies
aimed
at
promoting
remyelination
slowing
disease
progression
for
individuals
with
Here,
we
found
that
protein
kinase
C
(PKC)–modulating
drug
bryostatin-1
(bryo-1),
a
CNS-penetrant
compound
established
human
safety
profile,
shifts
transcriptional
programs
CNS-associated
from
proinflammatory
phenotype
vitro
vivo.
Treatment
bryo-1
stimulated
scavenger
pathways,
phagocytosis,
secretion
factors
prevented
neuroinflammatory
reactive
astrocytes
while
also
neuroaxonal
health
oligodendrocyte
differentiation.
line
findings,
systemic
treatment
mice
augmented
after
focal
demyelinating
injury.
Our
results
demonstrate
potential
possibly
wider
class
PKC
modulators
as
myelin-regenerative
supportive
agents
MS
other
neurologic
diseases.
Biomedicines,
Год журнала:
2025,
Номер
13(2), С. 357 - 357
Опубликована: Фев. 4, 2025
Background:
Multiple
sclerosis
(MS)
pathology
is
characterized
by
acute
and
chronic
inflammation,
demyelination,
axonal
injury,
neurodegeneration.
After
decades
of
research
into
MS-related
degeneration,
recent
efforts
have
shifted
toward
recovery
the
prevention
further
damage.
A
key
area
focus
remyelination
process,
where
researchers
are
studying
effects
pharmacotherapy
on
myelin
repair
mechanisms.
compounds
being
tested
for
their
potential
to
foster
in
different
clinical
settings
through
application
less
or
more
complex
techniques
assess
efficacy.
Objective:
To
review
current
methods
biomarkers
track
regeneration
over
time
people
with
MS
(PwMS),
implications
promyelinating
drug
testing.
Methods:
Narrative
review,
based
a
selection
PubMed
articles
discussing
measure
vivo
functional
PwMS.
Results:
Non-invasive
tools,
such
as
structural
Magnetic
Resonance
Imaging
(MRI)
Positron
Emission
Tomography
(PET),
implemented
repair,
while
other
like
evoked
potentials,
MRI,
digital
markers
allow
assessment
recovery.
These
methods,
alone
combination,
been
employed
obtain
precise
various
trials
MS.
Conclusions:
Combining
identify
restoration
could
yield
novel
biomarkers,
enhancing
accuracy
trial
outcomes
remyelinating
therapies
European Journal of Nuclear Medicine and Molecular Imaging,
Год журнала:
2021,
Номер
49(4), С. 1275 - 1287
Опубликована: Дек. 7, 2021
Abstract
The
reactive
astrocytes
manifest
molecular,
structural,
and
functional
remodeling
in
injury,
infection,
or
diseases
of
the
CNS,
which
play
a
critical
role
pathological
mechanism
neurological
diseases.
A
growing
need
exists
for
dependable
approach
to
better
characterize
activation
astrocyte
vivo.
As
an
advanced
molecular
imaging
technology,
positron
emission
tomography
(PET)
has
potential
visualizing
biological
activities
at
cellular
levels.
In
review,
we
summarized
PET
visualization
strategies
discussed
applications
Future
studies
are
needed
pay
more
attention
development
specific
agents
further
improve
our
exploration
various
Brain Communications,
Год журнала:
2023,
Номер
5(3)
Опубликована: Янв. 1, 2023
Abstract
Cognitive
impairment
occurs
in
40–65%
of
persons
with
multiple
sclerosis
and
may
be
related
to
alterations
glutamatergic
GABAergic
neurotransmission.
Therefore,
the
aim
this
study
was
determine
how
changes
relate
cognitive
functioning
vivo.
Sixty
(mean
age
45.5
±
9.6
years,
48
females,
51
relapsing-remitting
sclerosis)
22
age-matched
healthy
controls
(45.6
22.0
17
females)
underwent
neuropsychological
testing
MRI.
Persons
were
classified
as
cognitively
impaired
when
scoring
at
least
1.5
standard
deviations
below
normative
scores
on
≥30%
tests.
Glutamate
GABA
concentrations
determined
right
hippocampus
bilateral
thalamus
using
magnetic
resonance
spectroscopy.
GABA-receptor
density
assessed
quantitative
[11C]flumazenil
positron
emission
tomography
a
subset
participants.
Positron
outcome
measures
influx
rate
constant
(a
measure
predominantly
reflecting
perfusion)
volume
distribution,
which
is
density.
Twenty
(33%)
fulfilled
criteria
for
impairment.
No
differences
observed
glutamate
or
between
controls,
preserved,
control
groups.
Twenty-two
(12
preserved
10
impaired)
successfully
tomography.
showed
lower
thalamus,
indicating
perfusion.
For
higher
values
than
deep
grey
matter,
increased
When
comparing
patients
group
significantly
distribution
cortical
matter
hippocampus.
Positive
correlations
both
information
processing
speed
only.
Whereas
did
not
differ
nor
impaired,
groups,
that
seen
patients.
In
addition,
correlated
cognition,
particular
speed.
This
could
indicate
upregulated
phase
means
regulate
neurotransmission
potentially
preserve
functioning.
Current Opinion in Neurology,
Год журнала:
2023,
Номер
36(3), С. 214 - 221
Опубликована: Апрель 17, 2023
Purpose
of
review
Choroid
plexuses
(ChPs)
are
key
actors
the
blood-to-cerebrospinal-fluid
barrier
and
serve
as
brain
immune
checkpoint.
The
past
years
have
seen
a
regain
interest
about
their
potential
involvement
in
physiopathology
neuroinflammatory
disorders
like
multiple
sclerosis
(MS).
This
article
offers
an
overview
recent
findings
on
ChP
alterations
MS,
with
focus
imaging
tools
able
to
detect
these
abnormalities
inflammation,
tissue
damage
repair.
Recent
On
MRI,
ChPs
enlarged
people
MS
(PwMS)
versus
healthy
individuals.
size
increase
is
early
event,
already
detected
presymptomatic
pediatric
MS.
Enlargement
linked
local
inflammatory
infiltrates,
dysfunction
selectively
impacts
periventricular
damage,
larger
predicting
expansion
chronic
active
lesions,
smoldering
inflammation
remyelination
failure
tissues
surrounding
ventricles.
volumetry
may
add
value
for
prediction
disease
activity
disability
worsening.
Summary
metrics
emerging
possible
biomarkers
neuroinflammation
repair
Future
works
combining
multimodal
techniques
should
provide
more
refined
characterization
functional
changes,
link
blood
cerebrospinal-fluid
fluid
trafficking