Frontiers in Cellular Neuroscience,
Год журнала:
2022,
Номер
16
Опубликована: Июнь 16, 2022
Chronic
cerebral
hypoperfusion
(CCH)
is
a
major
cause
of
vascular
cognitive
impairment
and
dementia
(VCID).
Although
the
underlying
mechanisms
have
not
been
fully
elucidated,
emerging
data
suggest
that
blood-brain
barrier
(BBB)
dysfunction
one
pivotal
pathological
changes
in
CCH.
BBB
appears
early
CCH,
contributing
to
deterioration
white
matter
development
impairment.
In
this
review,
we
summarize
latest
experimental
clinical
evidence
implicating
disruption
as
VCID.
We
discuss
focusing
on
cell
interactions
within
BBB,
well
potential
role
APOE
genotype.
summary,
provide
novel
insights
into
pathophysiological
benefits
therapeutic
interventions
targeting
Seminars in Cell and Developmental Biology,
Год журнала:
2022,
Номер
139, С. 73 - 83
Опубликована: Май 24, 2022
Alzheimer's
disease
(AD)
is
a
neurodegenerative
disorder
that
by
affecting
specific
brain
cell
types
and
regions
cause
severe
pathological
functional
changes
in
memory
neural
circuits.
A
comprehensive
knowledge
of
the
pathogenic
mechanisms
underlying
AD
requires
deeper
understanding
cell-specific
responses
through
integrative
molecular
analyses.
Recent
application
high-throughput
single-cell
transcriptomics
to
postmortem
tissue
has
proved
powerful
unravel
susceptibility
biological
networks
responding
amyloid
tau
pathologies.
Here,
we
review
transcriptomic
studies
successfully
applied
decipher
gene
expression
programs
pathways
patients.
Transcriptional
information
reveals
both
common
signatures
major
cerebral
types,
including
astrocytes,
endothelial
cells,
microglia,
neurons,
oligodendrocytes.
Cell
type-specific
transcriptomes
associated
with
pathology
clinical
symptoms
are
related
affecting,
among
others
pathways,
synaptic
function,
inflammation,
proteostasis,
death,
oxidative
stress,
myelination.
The
general
picture
emerges
from
systems-level
spatiotemporal
pattern
diversity
novel
subpopulations
affected
brain.
We
argue
broader
implementation
larger
human
cohorts
using
standardized
protocols
fundamental
for
reliable
assessment
temporal
regional
cell-type
profiling.
possibility
applying
this
methodology
personalized
medicine
clinics
still
challenging
but
opens
new
roads
future
diagnosis
treatment
dementia.
Animal Models and Experimental Medicine,
Год журнала:
2023,
Номер
6(4), С. 337 - 345
Опубликована: Июнь 14, 2023
Abstract
Pericytes
are
the
main
cellular
components
of
tiny
arteries
and
capillaries.
Studies
have
found
that
pericytes
can
undergo
morphological
contraction
or
relaxation
under
stimulation
by
cytokines,
thus
affecting
microvessels
playing
an
essential
role
in
regulating
vascular
microcirculation.
Moreover,
due
to
characteristics
stem
cells,
differentiate
into
a
variety
inflammatory
cell
phenotypes,
which
then
affect
immune
function.
Additionally,
also
participate
angiogenesis
wound
healing
interacting
with
endothelial
cells
microcirculation
disorders.
Here
we
review
origin,
biological
phenotype
function
pericytes,
discuss
potential
mechanisms
disorders,
especially
pulmonary
hypertension,
so
as
provide
sound
basis
direction
for
prevention
treatment
diseases.
Fluids and Barriers of the CNS,
Год журнала:
2023,
Номер
20(1)
Опубликована: Окт. 24, 2023
Abstract
The
brain
is
a
highly
metabolically
active
organ
requiring
large
amount
of
glucose.
Methylglyoxal
(MGO),
by-product
glucose
metabolism,
known
to
be
involved
in
microvascular
dysfunction
and
associated
with
reduced
cognitive
function.
Maintenance
the
blood-brain
barrier
(BBB)
essential
maintain
optimal
function
evidence
indicates
negative
effects
MGO
on
BBB
integrity.
In
this
review,
we
summarized
current
literature
effect
different
cell
types
forming
BBB.
damage
by
most
likely
occurs
endothelial
cells
mural
cells,
while
astrocytes
are
resistant
MGO.
Microglia
other
hand
appear
not
directly
influenced
but
rather
produce
upon
activation.
Although
there
clear
that
affects
components
BBB,
impact
as
multicellular
system
warrants
further
investigation.
Diminishing
stress
can
potentially
form
basis
for
new
treatment
strategies
maintaining
International Journal of Molecular Sciences,
Год журнала:
2023,
Номер
24(17), С. 13114 - 13114
Опубликована: Авг. 23, 2023
Small
vessel
disease
(SVD)
is
a
highly
prevalent
disorder
of
the
brain's
microvessels
and
common
cause
dementia
as
well
ischaemic
haemorrhagic
strokes.
Though
much
about
underlying
pathophysiology
SVD
remains
poorly
understood,
wealth
recently
published
evidence
strongly
suggests
key
role
microvessel
endothelial
dysfunction
compromised
blood-brain
barrier
(BBB)
in
development
progression
disease.
Understanding
causes
downstream
consequences
associated
with
this
pathological
context
could
aid
effective
diagnostic
prognostic
tools
provide
promising
avenues
for
potential
therapeutic
interventions.
In
scoping
review,
we
aim
to
summarise
findings
from
clinical
studies
examining
molecular
mechanisms
SVD,
focussing
on
biochemical
markers
detectable
biofluids,
including
cell
adhesion
molecules,
BBB
transporters,
cytokines/chemokines,
inflammatory
markers,
coagulation
factors,
growth
involved
nitric
oxide
cascade.
Journal of Clinical Investigation,
Год журнала:
2024,
Номер
134(6)
Опубликована: Март 14, 2024
Allergic
asthma
generally
starts
during
early
life
and
is
linked
to
substantial
tissue
remodeling
lung
dysfunction.
Although
angiogenesis
a
feature
of
the
disrupted
airway,
impact
allergic
on
pulmonary
microcirculation
unknown.
Here,
using
quantitative
imaging
in
precision-cut
slices
(PCLSs),
we
report
that
exposure
neonatal
mice
house
dust
mite
(HDM)
extract
disrupts
endothelial
cell/pericyte
interactions
adventitial
areas.
Central
blood
vessel
structure,
loss
pericyte
coverage
was
driven
by
mast
cell
(MC)
proteases,
such
as
tryptase,
can
induce
retraction
critical
adhesion
molecule
N-cadherin.
Furthermore,
spatial
transcriptomics
pediatric
asthmatic
endobronchial
biopsies
suggests
intense
vascular
stress
with
increased
expression
MC
activation
pathways
regions
enriched
vessels.
These
data
provide
previously
unappreciated
insights
into
pathophysiology
potential
long-term
defects.
Pharmacological Reviews,
Год журнала:
2025,
Номер
77(3), С. 100052 - 100052
Опубликована: Март 13, 2025
High
fidelity
neuronal
signaling
is
enabled
by
a
stable
local
microenvironment.
A
high
degree
of
homeostatic
regulation
the
brain
microenvironment,
and
its
separation
from
variable
potentially
neurotoxic
contents
blood,
brought
about
central
nervous
system
barriers.
Evidence
clinical
preclinical
studies
implicates
microcirculation,
cerebral
hypoperfusion,
blood-brain
barrier
dysfunction,
reduced
amyloid
clearance
in
Alzheimer
pathophysiology.
Studying
this
dysregulation
key
to
understanding
disease
(AD),
identifying
drug
targets,
developing
treatment
strategies,
improving
prescribing
vulnerable
population.
This
review
has
2
parts:
part
1
describes
blood
flow,
extracellular
fluid
drainage,
neurovascular
unit
components
with
an
emphasis
on
barrier,
summarizes
how
each
aspect
altered
AD.
Discussing
structures
separately
allows
us
conclude
that
aberrant
pericytes
are
early
contributor
AD
Pericytes
have
multiple
functions
including
maintenance
integrity
control
capillary
stalling,
coupling,
intramural
periarterial
glia-lymphatic
(glymphatic)
consequently
tau
clearance.
vasoactive,
express
cholinergic
adrenergic
receptors,
exhibit
apolipoprotein
E
isoform-specific
transport
pathways.
Hypoperfusion
linked
pericyte-mediated
response.
Deficient
endothelial
cell-pericyte
(PDGBB-PDGFRβ)
loops
cause
pericyte
which
contributes
even
initiates
degeneration.
We
pathophysiology,
interesting
therapeutic
target
AD,
emerging
role
regenerative
therapy.
SIGNIFICANCE
STATEMENT:
Dysregulation
dysfunction
circulation
(including
cerebrospinal
fluid,
interstitial
fluid)
occurs
disease.
player
pericyte.
fundamental
implications
pathophysiology
development
therapies.
Diagnostics,
Год журнала:
2021,
Номер
11(9), С. 1525 - 1525
Опубликована: Авг. 24, 2021
Neuroinflammation
represents
a
central
feature
in
the
development
of
Alzheimer’s
disease
(AD).
The
resident
innate
immune
cells
brain
are
principal
players
neuroinflammation,
and
their
activation
leads
to
defensive
response
aimed
at
promoting
β-amyloid
(Aβ)
clearance.
However,
it
is
now
widely
accepted
that
peripheral
system—by
virtue
dysfunctional
blood–brain
barrier
(BBB)—is
involved
pathogenesis
progression
AD;
microglial
astrocytic
release
chemokines
able
recruit
into
nervous
system
(CNS);
same
time,
cytokines
released
by
cross
BBB
act
upon
glial
cells,
modifying
phenotype.
To
successfully
fight
this
neurodegenerative
disorder,
accurate
sensitive
biomarkers
required
be
used
for
implementing
an
early
diagnosis,
monitoring
treatment
effectiveness.
Interestingly,
as
result
bidirectional
communication
between
periphery,
blood
compartment
ends
up
reflecting
several
pathological
changes
occurring
AD
can
represent
accessible
source
such
biomarkers.
In
review,
we
provide
overview
on
some
most
promising
discussing
pathogenic
role
AD.
