Neurovascular unit, neuroinflammation and neurodegeneration markers in brain disorders
Frontiers in Cellular Neuroscience,
Год журнала:
2024,
Номер
18
Опубликована: Окт. 25, 2024
Neurovascular
unit
(NVU)
inflammation
via
activation
of
glial
cells
and
neuronal
damage
plays
a
critical
role
in
neurodegenerative
diseases.
Though
the
exact
mechanism
disease
pathogenesis
is
not
understood,
certain
biomarkers
provide
valuable
insight
into
pathogenesis,
severity,
progression
therapeutic
efficacy.
These
markers
can
be
used
to
assess
pathophysiological
status
brain
including
neurons,
astrocytes,
microglia,
oligodendrocytes,
specialized
microvascular
endothelial
cells,
pericytes,
NVU,
blood-brain
barrier
(BBB)
disruption.
Damage
or
derangements
tight
junction
(TJ),
adherens
(AdJ),
gap
(GJ)
components
BBB
lead
increased
permeability
neuroinflammation
various
disorders
disorders.
Thus,
neuroinflammatory
evaluated
blood,
cerebrospinal
fluid
(CSF),
tissues
determine
neurological
progression,
responsiveness.
Chronic
common
age-related
Alzheimer's
(AD),
Parkinson's
(PD),
dementia.
Neurotrauma/traumatic
injury
(TBI)
also
leads
acute
chronic
responses.
The
expression
some
may
altered
many
years
even
decades
before
onset
In
this
review,
we
discuss
neuroinflammation,
neurodegeneration
associated
with
disorders,
especially
those
neurovascular
pathologies.
CSF,
tissues.
Neurofilament
light
(NfL),
ubiquitin
C-terminal
hydrolase-L1
(UCHL1),
fibrillary
acidic
protein
(GFAP),
Ionized
calcium-binding
adaptor
molecule
1
(Iba-1),
transmembrane
119
(TMEM119),
aquaporin,
endothelin-1,
platelet-derived
growth
factor
receptor
beta
(PDGFRβ)
are
important
markers.
Recent
BBB-on-a-chip
modeling
offers
promising
potential
for
providing
an
in-depth
understanding
neurotherapeutics.
Integration
these
clinical
practice
could
potentially
enhance
early
diagnosis,
monitor
improve
outcomes.
Язык: Английский
The blood-brain barrier as a treatment target for neurodegenerative disorders
Expert Opinion on Drug Delivery,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 17, 2025
Introduction
The
blood-brain
barrier
(BBB)
is
a
vascular
endothelial
membrane
which
restricts
entry
of
toxins,
cells
and
microorganisms
into
the
brain.
At
same
time,
BBB
supplies
brain
with
nutrients,
key
substrates
for
DNA
RNA
synthesis,
regulatory
molecules,
removes
metabolic
waste
products
from
to
blood.
breakdown
and/or
dysfunction
have
been
shown
in
neurogenerative
disorders
including
Alzheimer's
disease
(AD).
Current
data
suggests
that
these
changes
may
initiate
contribute
neuronal,
synaptic
cognitive
dysfunction,
possibly
other
aspects
neurodegenerative
processes.
Язык: Английский
Engineered nanoparticles for the treatment of Alzheimer’s disease
Frontiers in Pharmacology,
Год журнала:
2025,
Номер
16
Опубликована: Апрель 3, 2025
Alzheimer’s
disease
(AD)
is
one
of
the
most
common
diseases
characterized
by
neurodegeneration
and
becoming
a
major
public
health
problem
worldwide.
AD
manifested
mainly
progressive
impairments
in
cognition,
emotion,
language
memory
elderly
population.
Many
treatment
strategies
have
been
explored
for
decades;
however,
there
still
no
effective
way
to
address
root
cause
pathogenesis,
only
target
symptoms
improve
patient
cognitive
outcomes.
Intracerebral
administration
difficult
because
challenges
posed
blood‒brain
barrier
(BBB).
NPs
are
materials
with
sizes
between
1
100
nm
that
can
biocompatibility,
extend
half-life,
transport
macromolecules,
be
delivered
across
BBB
central
nervous
system,
exhibit
good
targeting
capabilities.
provide
new
ideas
terms
their
antiaging,
antineuroinflammatory,
antioxidative,
nerve
repair-promoting
effects.
In
this
manuscript,
we
first
describe
relationship
BBB.
Second,
introduce
application
nanoparticles
treatment.
Finally,
summarize
faced
AD.
Язык: Английский
Evidence Suggesting Prolonged Neuroinflammation in a Subset of Children after Moderate/Severe TBI: A UCLA RAPBI Study
medRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 22, 2025
Abstract
Traumatic
brain
injury
(TBI)
presents
a
public
health
concern
as
leading
cause
of
death
and
disability
in
children.
Pediatric
populations
are
particularly
vulnerable
to
adverse
outcomes
following
TBI
due
periods
rapid
growth,
synaptic
pruning,
myelination.
patients
with
moderate-severe
(msTBI)
healthy
controls
were
evaluated
from
the
post-acute
(2-5
months)
chronic
phase
(13-19
recovery
using
diffusion
magnetic
resonance
imaging
(dMRI)
interhemispheric
transfer
time
(IHTT),
which
is
an
event-related
potential
measure
speed
information
across
corpus
callosum.
We
previously
identified
two
subgroups
based
on
IHTT,
one
group
showing
significantly
slower
IHTT
(TBI-slow),
poorer
cognitive
performance,
progressive
structural
damage.
In
contrast,
other
(TBI-normal)
did
not
differ
or
performance
showed
relative
over
time.
Here,
we
examined
differences
restricted
(RDI),
dMRI
metric
sensitive
inflammation.
Comparing
TBI-slow,
TBI-normal,
RDI
cross-sectionally,
connectometry
analysis
revealed
higher
white
matter
TBI-slow
compared
both
control
TBI-normal
groups.
Longitudinal
analyses
indicated
that
while
groups
exhibited
decrease
time,
suggesting
resolution
neuroinflammation
recovery,
decreases
smaller.
The
between
suggest
inflammation
may
play
key
role
prolonged
including
structure,
symptom
reports,
pediatric
msTBI.
Язык: Английский
Artificial intelligence-driven prediction and validation of blood-brain barrier permeability and absorption, distribution, metabolism, excretion profiles in Natural Product Research Laboratory compounds
Biomedicine,
Год журнала:
2024,
Номер
14(4)
Опубликована: Дек. 1, 2024
Introduction:
Our
previous
research
demonstrated
that
a
large
language
model
(LLM)
based
on
the
transformer
architecture,
specifically
MegaMolBART
encoder
with
an
XGBoost
classifier,
effectively
predicts
blood-brain
barrier
(BBB)
permeability
of
compounds.
However,
coefficients
compounds
can
traverse
this
remain
unclear.
Additionally,
absorption,
distribution,
metabolism,
and
excretion
(ADME)
characteristics
substances
obtained
from
Natural
Product
Research
Laboratory
(NPRL)
at
China
Medical
University
Hospital
(CMUH)
have
not
yet
been
determined.
Язык: Английский
Bursts of brain erosion: seizures and age-dependent neurological vulnerability
Trends in Molecular Medicine,
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 1, 2024
Язык: Английский
Evaluation of Blood–Brain Barrier Disruption Using Low- and High-Molecular-Weight Complexes in a Single Brain Sample in a Rat Traumatic Brain Injury Model: Comparison to an Established Magnetic Resonance Imaging Technique
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(20), С. 11241 - 11241
Опубликована: Окт. 19, 2024
Traumatic
brain
injury
(TBI),
a
major
cause
of
death
and
disability
among
young
people,
leads
to
significant
public
health
economic
challenges.
Despite
its
frequency,
treatment
options
remain
largely
unsuitable.
However,
examination
the
blood–brain
barrier
(BBB)
can
assist
with
understanding
mechanisms
dynamics
dysfunction,
which
affects
TBI
sufferers
secondarily
injury.
Here,
we
present
rat
model
focused
on
two
standard
BBB
assessment
markers,
high-
low-molecular-weight
complexes,
in
order
understand
disruption.
In
addition,
tested
new
technique
evaluate
disruption
single
set,
comparing
neuroimaging.
A
total
100
Sprague–Dawley
rats
were
separated
into
following
five
groups:
naive
(n
=
20
rats),
control
administration
60
rats).
Rats
assessed
at
different
time
points
after
measure
using
low-
high-molecular-weight
complexes.
Neurological
severity
score
was
evaluated
baseline
24
h
TBI.
During
neurological
exam
TBI,
scanned
magnetic
resonance
imaging
euthanized
for
permeability.
We
found
that
markers
displayed
examples
same
set
tissues
over
period
week.
Our
innovative
protocol
assessing
permeability
complexes
showed
appropriate
results.
Additionally,
determined
lower
limit
sensitivity,
therefore
demonstrating
accuracy
this
method.
Язык: Английский
Editorial: 15 years of frontiers in cellular neuroscience: blood brain barrier modulation and dysfunction in brain diseases
Frontiers in Cellular Neuroscience,
Год журнала:
2024,
Номер
18
Опубликована: Окт. 29, 2024
The
blood-brain
barrier
(BBB)
is
a
dynamic
structure
that
regulates
transport
(influx
and
efflux)
of
molecules
between
brain
parenchyma
blood
circulation
protects
the
from
various
pathogens,
neurotoxic
periphery
(Zapata-Acevedo
et
al.,
2024)
drugs
(Ronaldson
Davis,
2024).
These
protective
actions
are
achieved
due
to
presence
tight
junctions
(TJ)
with
claudin
5,
occluden,
junctional
adhesion
(JAMs),
zonula
occludens-1
(ZO-1),
adherens
(AJ)
Ve-Cadherin,
catenin,
gap
(GJ)
connexins
adjacent
endothelial
cells
provide
physical
peripheral
(Kempuraj
2020;Andjelkovic
2023;Haruwaka
2019).
Microvascular
in
express
many
transporters
regulate
molecules,
including
glucose.
Neurovascular
unit
(NVU)
consists
microvascular
cells,
astrocytes,
pericytes
(overall
forming
BBB)
neurons.
An
intact
BBB
maintains
homeostasis
microenvironment
for
normal
neuronal
signaling,
while
disrupted
BBB,
derangement
junction
proteins
associated
increased
permeability
observed
neuroinflammatory
neurodegenerative
disorders
(Sweeney
2018;Kempuraj
2020).
Neuroinflammation
plays
an
important
role
such
as
chronic
diseases
Alzheimer's
disease,
Parkinson's
Multiple
Sclerosis
(MS),
stroke,
traumatic
injury
(TBI)
Systemic
inflammatory
can
cause
exacerbate
responses
(Paouri
Georgopoulos,
2019;Cheng
2022).
This
research
topic
"Blood-brain
modulation
dysfunction
diseases"
presents
collection
following
articles
demonstrate
disruption
pathogenesis
how
it
be
therapeutically
overcome.Gemfibrozil
lipid-lowering
drug
showed
neuroprotective
effects
by
inhibiting
glial
inflammation,
oxidative
stress
apoptosis
(Ivraghi
A
previous
study
has
shown
gemfibrozil's
therapeutic
beneficial
experimental
autoimmune
encephalomyelitis
(EAE),
animal
model
demyelinating
disease
MS
(Dasgupta
2007).
Gemfibrozil
known
suppress
expression
through
its
ligand
peroxisome
proliferator-activated
receptor
alpha
(PPARα).
paper
Mondal
al.
this
special
shows
gemfibrozil
integrity
BBB/blood-spinal
cord
(BSB),
enhances
Tregs,
decreases
EAE
PPARβ,
but
not
PPARα
mice
(Mondal
Further,
above
indicates
immunomodulatory
PPARβ
may
explored
intervention
2024).Pericytes
flow
thus
contribute
pathophysiology
NVU
(Bhowmick
Pericytes
highly
plastic
contractile
microvessels,
maintenance
integrity,
angiogenesis,
control
leukocyte
transmigration
(Alarcon-Martinez
2021).
In
their
review
article
topic,
Fu
highlight
pericyte
biomarkers,
stem
cell
paracrine
functions,
neuroinflammation
especially
ischemic
stroke
(Fu
2023).
these
authors
suggest
could
targets
disorders,
TBI
provides
significant
current
information
on
fundamental
still
partially
unknown
contributors
NVU/BBB
functions
2023).Oxidative
causes
damage
TBI.
Inhibition
histone
deacetylases
(HDACs)
been
decrease
level
reducing
reactive
oxygen
species
(Lu
paper,
Inoue
studied
mechanism
HDAC
inhibition
using
vascular
(Inoue
They
report
incubation
immortalized
human
(HCMEC/D3)
treated
W2A-16
(an
inhibitor)
retained
property
trans-endothelial
electrical
resistance
(TEER)
levels
compared
untreated
cells.
study,
were
cultured
hydrogen
peroxidase
then
medium
was
switched
or
without
cultured.
concludes
formation
2024).Microglia
brain-resident
immune
present
M0
(resting),
M1
(proinflammatory)
M2
anti-inflammatory
phenotypes
(Wendimu
Hooks,
Microglial
activation
implicated
diseases.
recent
discussed
microglia
health
(Mayer
Fischer,
Deng
crosstalk
communication
brain,
heart,
spleen
after
(Deng
discuss
microglia-associated
network
inflammation
induces
cardiovascular
disorders.
they
indicate
involve
permeability,
entry
into
brain-derived
organs
monocytes
2023).Detection
biomarkers
cerebrospinal
fluid
(CSF),
blood,
tissues,
validation
vitro
culture
models
useful
diagnoses
assessing
severity
components
(Kadry
Kempuraj
overview
most
markers
NVU/BBB,
expressed
D,
derangements
TJ,
AJ,
GJ
lead
resulting
edema,
2024).Additionally,
highlights
BBB-on-a-chip
modeling
offers
promising
potential
pre-clinical
in-depth
understanding
pathologies
neurotherapeutics.Neuroinflammatory
show
dysfunctions
permeability.
Understanding
mechanisms
underlying
pathological
events
assessment
identify
innovative
treatment
options
several
insights
which
development
more
effective
Язык: Английский
Alteration of Serum MLKL Levels and Their Association with Severity and Clinical Outcomes in Human Severe Traumatic Brain Injury: A Prospective Cohort Study
Yidong Jin,
Han Zhang,
Min Zhou
и другие.
International Journal of General Medicine,
Год журнала:
2024,
Номер
Volume 17, С. 5069 - 5084
Опубликована: Ноя. 1, 2024
Background:
Mixed
lineage
kinase
domain-like
protein
(MLKL),
which
modulates
necroptosis,
has
been
implicated
in
pathophysiological
processes
following
acute
brain
injury.
Here,
serum
MLKL
was
quantified
to
determine
its
prognostic
significance
severe
traumatic
injury
(sTBI).
Methods:
This
prospective
cohort
study
enrolled
155
patients
with
sTBI
and
healthy
volunteers.
The
severity
metrics
included
the
Glasgow
Coma
Scale
(GCS)
score
Rotterdam
computed
tomography
(CT)
classification.
extended
outcome
scale
(GOSE)
at
posttraumatic
180
days
considered
as
a
parameter,
of
1–
4
indicating
poor
prognosis.
Univariate
subsequent
multivariate
analyses
were
used
for
independent
factorial
investigation.
Results:
Compared
controls,
displayed
profoundly
elevated
levels.
In
framework
restricted
cubic
spline
analysis,
levels
linearly
correlated
likelihood
mortality,
overall
survival,
Serum
not
only
independently
GCS,
CT
scores
GOSE
scores,
but
also
predictive
death,
Subgroup
analysis
showed
that
exhibited
negligible
interactions
age,
sex,
hypertension,
diabetes,
smoking
habits,
alcohol
consumption
distinguish
possibility
Within
context
receiver
operating
characteristic
curve
had
strong
discrimination
effectiveness
death
prognosis
and,
contrast
GCS
have
equivalent
ability.
Conclusion:
Extreme
elevation
is
intimately
related
trauma
severity,
neurological
outcomes,
suggesting
may
act
potential
predictor
facilitating
stratification
prediction
sTBI.
Keywords:
injury,
mixed
protein,
outcome,
biomarkers
Язык: Английский