S S Korsakov Journal of Neurology and Psychiatry,
Год журнала:
2023,
Номер
123(9), С. 58 - 58
Опубликована: Янв. 1, 2023
To
identify
the
role
of
changes
in
expression
inflammation-related
genes
cerebral
microangiopathy/cerebral
small
vessel
disease
(cSVD).Forty-four
cSVD
patients
(mean
age
61.4±9.2)
and
11
controls
57.3±9.7)
were
studied.
Gene
was
assessed
on
an
individual
NanoString
nCounter
panel
58
4
reference
genes.
A
set
generated
based
converging
results
complete
genome-wide
association
studies
(GWAS)
Alzheimer's
(AD)
circulating
markers
associated
with
vascular
wall
Brain
lesions
cSVD.
RNA
isolated
from
blood
leukocytes
analyzed
Analysis
System,
followed
by
analysis
nSolver
4.0.
Results
verified
real-time
PCR.CSVD
had
a
significant
decrease
BIN1
(log2FC=-1.272;
p=0.039)
VEGFA
(log2FC=-1.441;
p=0.038)
compared
to
controls,
which
showed
predictive
ability
for
The
cut-off
5.76
a.u.
(sensitivity
73%;
specificity
75%)
9.27
64%;
86%).
Reduced
(p=0.011),
VEGFC
(p=0.017),
CD2AP
(p=0.044)
cognitive
impairment
(CI).
There
direct
correlation
between
scores
Montreal
Cognitive
Assessment
test
delayed
memory.The
possible
prediction
reduced
levels
BIN1,
clinically
CI
indicate
their
importance
development
progression
disease.
established
these
pathogenesis
AD
suggests
that
similar
profile
may
be
one
conditions
comorbidity
two
pathologies.Уточнить
роль
изменения
экспрессии
генов,
ассоциированных
с
воспалением,
при
церебральной
микроангиопатии
(ЦМА).Обследованы
44
пациента
ЦМА
(средний
возраст
61,4±9,2
года)
и
добровольцев
57,3±9,7
года).
Экспрессия
генов
оценивалась
на
индивидуальной
панели
из
эталонных
генов.
Набор
сформирован
основе
конвергирующих
результатов
полногеномных
исследований
ассоциаций
болезни
Альцгеймера
циркулирующих
маркеров,
поражением
сосудистой
стенки
мозга
ЦМА.
РНК
выделяли
лейкоцитов
крови
анализировали
помощью
последующий
анализ
проводили
в
Результаты
проверяли
методом
ПЦР
режиме
реального
времени.Пациенты
по
сравнению
контролем
имели
значимое
снижение
(log2FC=–1,272;
p=0,039)
(log2FC=–1,441;
p=0,038),
которые
показали
предиктивную
способность
отношении
Пороговое
значение
5,76
у.е.
(чувствительность
73%,
специфичность
75%),
9,27
64%,
Снижение
(p=0,011),
(p=0,017),
(p=0,044)
было
связано
клинически
выраженными
когнитивными
расстройствами.
Выявлена
значимая
прямая
корреляционная
связь
результата
тестирования
Монреальской
шкале
оценки
когнитивных
функций
экспрессией
VEGFC;
теста
отсроченного
запоминания
—
VEGFC.Возможность
предикции
развития
сниженному
уровню
значимых
расстройств
со
снижением
указывают
их
развитии
прогрессировании
заболевания.
Установленная
значимость
данных
патогенезе
указывает
то,
что
сходные
профиля
могут
быть
одним
условий
коморбидности
двух
патологий.
Biomedicines,
Год журнала:
2022,
Номер
10(9), С. 2261 - 2261
Опубликована: Сен. 13, 2022
Alzheimer's
disease
(AD)
is
the
most
common
cause
of
neurodegenerative
dementia,
whilst
Parkinson's
(PD)
a
movement
disorder.
These
two
disorders
share
accumulation
toxic
proteins
as
pathological
hallmark.
The
lack
definitive
disease-modifying
treatments
for
these
neurogenerative
diseases
has
led
to
hypothesis
new
pathogenic
mechanisms
target
and
design
potential
therapeutic
approaches.
recent
observation
that
glymphatic
system
supposed
be
responsible
cerebrospinal
fluid
into
brain
clearance
metabolic
waste
study
its
involvement
in
pathogenesis
classic
proteinopathies.
Aquaporin-4
(AQP4),
water
channel
located
endfeet
astrocyte
membrane,
considered
primary
driver
system,
defective
AQP4-mediated
drainage
been
linked
objective
present
review
body
knowledge
links
AD
PD
other
lifestyle
factors
such
sleep
deprivation
exercise
may
influence
function.
We
will
also
focus
on
neuroimaging
approaches
could
identify
marker
detect
changes.
Theranostics,
Год журнала:
2024,
Номер
14(5), С. 1909 - 1938
Опубликована: Янв. 1, 2024
Rationale:
Hydrocephalus
is
a
substantial
complication
after
intracerebral
hemorrhage
(ICH)
or
intraventricular
(IVH)
that
leads
to
impaired
cerebrospinal
fluid
(CSF)
circulation.Recently,
brain
meningeal
lymphatic
vessels
(mLVs)
were
shown
serve
as
critical
drainage
pathways
for
CSF.Our
previous
studies
indicated
the
degradation
of
neutrophil
extracellular
traps
(NETs)
ICH/IVH
alleviates
hydrocephalus.However,
mechanisms
by
which
NET
exerts
beneficial
effects
in
hydrocephalus
remain
unclear.Methods:
A
mouse
model
following
IVH
was
established
infusing
autologous
blood
into
both
wildtype
and
Cx3cr1
-/-mice.By
studying
features
processes
model,
we
investigated
contribution
mLVs
NETs
development
progression
secondary
IVH.Results:
This
study
observed
widespread
presence
neutrophils,
fibrin
IVH,
alleviated
injury.Importantly,
improved
CSF
enhancing
recovery
endothelial
cells
(LECs).Furthermore,
our
showed
activated
membrane
protein
CX3CR1
on
LECs
IVH.In
contrast,
repair
promoted
ameliorated
knockdown
-/-mice.Conclusion:
Our
findings
participate
injury
contribute
acute
LEC
thrombosis.CX3CR1
key
molecule
NET-induced
damage
thrombosis,
mLV
dysfunction
exacerbates
injury.NETs
may
be
target
preventing
obstruction
IVH.
Neurobiology of Disease,
Год журнала:
2025,
Номер
205, С. 106791 - 106791
Опубликована: Янв. 6, 2025
Neurodegenerative
diseases
(ND)
are
characterized
by
the
accumulation
of
aggregated
proteins.
The
glymphatic
system,
through
its
rapid
exchange
mechanisms
between
cerebrospinal
fluid
(CSF)
and
interstitial
(ISF),
facilitates
movement
metabolic
substances
within
brain,
serving
functions
akin
to
those
peripheral
lymphatic
system.
This
emerging
waste
clearance
mechanism
offers
a
novel
perspective
on
removal
pathological
in
ND.
article
elucidates
recent
discoveries
regarding
system
updates
relevant
concepts
model.
It
discusses
potential
roles
ND,
including
Alzheimer's
disease
(AD),
Parkinson's
(PD),
multiple
atrophy
(MSA),
proposes
as
therapeutic
target
for
these
conditions.
Abstract
White
matter
hyperintensity
(WMH)
represents
a
critical
global
medical
concern
linked
to
cognitive
decline
and
dementia,
yet
its
underlying
mechanisms
remain
poorly
understood.
Here,
humans
are
directly
demonstrated
that
high
WMH
burden
correlates
with
delayed
drainage
of
meningeal
lymphatic
vessels
(mLVs)
glymphatic
pathway.
Additionally,
longitudinal
cohort
study
reveals
dysfunction
predicts
progression.
Next,
in
rat
model
WMH,
the
presence
impaired
lymphangiogenesis
is
confirmed,
followed
by
elevated
microglial
activation
white
demyelination.
Notably,
enhancing
through
adeno‐associated
virus
delivery
vascular
endothelial
growth
factor‐C
(VEGF‐C)
mitigates
gliosis
Conversely,
blocking
mLVs
VEGF‐C
trap
strategy
exacerbates
these
changes.
The
findings
highlight
role
pathway
aggravating
brain
injury,
providing
potential
novel
for
prevention
treatment.
Abstract
In
the
aging
process
and
central
nervous
system
(CNS)
diseases,
functions
of
meningeal
lymphatic
vessels
(MLVs)
are
impaired.
Alterations
in
MLVs
have
been
observed
aging-related
neurodegenerative
brain
tumors,
even
cerebrovascular
disease.
These
findings
reveal
a
new
perspective
on
CNS
disorders
provide
promising
therapeutic
target.
Additionally,
recent
neuropathological
studies
shown
that
exchange
soluble
components
between
cerebrospinal
fluid
(CSF)
interstitial
(ISF)
drain
metabolites,
cellular
debris,
misfolded
proteins,
immune
cells
from
CSF
into
deep
cervical
lymph
nodes
(dCLNs),
directly
connecting
with
peripheral
circulation.
Impairment
dysfunction
lymphatics
can
lead
to
accumulation
toxic
proteins
brain,
exacerbating
progression
neurological
disorders.
However,
for
many
causal
relationship
changes
is
not
fully
clear.
Here,
after
brief
historical
retrospection,
we
review
discoveries
about
hallmarks
their
roles
as
well
potential
targets
treatment
neurologic
diseases.
Cells,
Год журнала:
2023,
Номер
12(6), С. 957 - 957
Опубликована: Март 21, 2023
Brain
vascular
health
appears
to
be
critical
for
preventing
the
development
of
amyotrophic
lateral
sclerosis
(ALS)
and
slowing
its
progression.
ALS
patients
often
demonstrate
cardiovascular
risk
factors
commonly
suffer
from
cerebrovascular
disease,
with
evidence
pathological
alterations
in
their
small
cerebral
blood
vessels.
Impaired
brain
has
detrimental
effects
on
motor
neurons:
endothelial
growth
factor
levels
are
lowered
ALS,
which
can
compromise
cell
formation
integrity
blood–brain
barrier.
Increased
turnover
neurovascular
unit
cells
precedes
senescence,
which,
together
pericyte
alterations,
further
fosters
failure
toxic
metabolite
removal.
We
here
provide
a
comprehensive
overview
pathogenesis
impaired
how
novel
magnetic
resonance
imaging
techniques
aid
detection.
In
particular,
we
discuss
patterns
supply
cortex
number
branches
anterior
middle
arteries
acting
as
marker
resistance
resilience
against
downstream
events
ALS.
outline
certain
interventions
adapted
patient
needs
capabilities
have
potential
mechanistically
target
microvasculature
towards
favorable
patterns.
Through
this
strategy,
aim
guide
approaches
management
better
understanding
pathophysiology.
Aging and Disease,
Год журнала:
2023,
Номер
unknown
Опубликована: Янв. 1, 2023
The
aging
of
the
global
population
poses
significant
scientific
challenges.
Moreover,
biological
process
is
most
risk
factor
for
chronic
illnesses;
therefore,
understanding
molecular
and
cellular
mechanisms
underlying
these
aging-related
challenges
crucial
extending
healthy
lifespan
older
individuals.
Preventing
brain
remains
a
priority
public
health
goal,
integrative
comprehensive
analyses
have
revealed
that
immunosenescence
potential
cause
age-related
damage
disease
(e.g.,
stroke).
Importantly,
neuroinflammatory
immune
systems
present
two-way
contact
thus
can
affect
each
other.
Emerging
evidence
supports
numerous
effects
immunosenescence-
inflammation-mediated
immunity
in
neurologically
injured
brains.
In
this
study,
we
briefly
outline
how
alters
pathophysiology
transcriptional
amplitude
patients
who
experienced
stroke
then
discuss
system
its
components
are
affected
by
age
after
stroke.
Finally,
highlight
emerging
interventions
with
to
slow
down
or
reduce
prevent
onset.
Neurología (English Edition),
Год журнала:
2025,
Номер
40(3), С. 306 - 328
Опубликована: Апрель 1, 2025
The
complex
process
of
amyloid-β
(Aβ)
transportation
across
the
blood-brain
and
blood-cerebrospinal
fluid
barriers
is
crucial
for
preventing
Aβ
accumulation,
which
linked
to
dementia
neurodegeneration.
This
review
explores
therapeutic
plasma
exchange
with
albumin
replacement
in
Alzheimer's
disease,
based
on
dynamics
between
brain,
plasma,
cerebrospinal
fluid.
A
comprehensive
literature
was
conducted
using
PubMed/Medline,
Cochrane
Library,
open
databases
(bioRxiv,
MedRixv,
preprint.org)
up
April
30,
2023.
first
search
utilized
following
MeSH
terms
keywords:
'Plasma
Exchange',
'Plasmapheresis',
'Therapeutic
exchange',
'Apheresis',
'Aβ',
'p-tau',
'Total-tau',
'Alzheimer's
disease',
'Cognitive
dysfunction',
'neurodegenerative
diseases',
'centrifugation',
'membranous',
'filtration'
Title/Abstract,
yielding
146
results.
second
'Albumin',
'BBB',
dementia',
'Nerve
degeneration'
resulted
125
additional
articles
analysis.
Finally,
a
third
'Albumin
structural
domains',
'Albumin-Aβ
interactions',
'Albumin-endothelial
'Post-Translational
Modification'
produced
193
results
further
review.
Therapeutic
shows
potential
as
disease-modifying
therapy
dementia,
specifically
disease.
Additionally,
promising
role
supplementation
cognitive
improvement
has
attracted
attention.
However,
clinical
evidence
supporting
remains
limited,
necessitating
research
development
mitigate
adverse
effects.
deeper
understanding
molecular
mechanisms
essential.
critical
evaluation
existing
highlights
importance
balancing
benefits
associated
risks,
will
guide
application
these
treatments
neurodegenerative
diseases.