Alzheimer s & Dementia,
Journal Year:
2018,
Volume and Issue:
14(12), P. 1640 - 1650
Published: Aug. 14, 2018
Abstract
Introduction
Blood‐brain
barrier
(BBB)
breakdown
is
observed
in
older
versus
younger
adults
and
late‐onset
Alzheimer's
disease
age‐matched
controls,
but
its
causes
consequences
aging
are
unclear.
We
tested
the
hypothesis
that
BBB
associated
with
cognitive
decline
inflammation
nondemented
elders.
Methods
Cerebrospinal
fluid
serum
inflammatory
markers
were
measured
using
sandwich
immunoassays
120
subjects.
Least
Absolute
Shrinkage
Selection
Operator‐logistic
regression
selected
cerebrospinal
signatures
best
classified
impairment
defined
by
albumin
index
≥9.
Linear
examined
changes
Clinical
Dementia
Rating
sum
of
boxes
as
a
function
integrity
at
baseline.
Results
Mean
age
was
70
years,
mean
Mini–Mental
State
Examination
27,
recorded
13.5%.
(
P
=
.015).
intercellular
adhesion
molecule‐1,
vascular
endothelial
growth
factor,
interleukin‐8,
amyloid
A,
macrophage
derived
chemokine,
gender
generated
an
area
under
curve
0.95
for
impairment,
IL‐16,
VEGF‐D,
IL‐15,
other
variables
AUC
0.92
impairment.
Discussion
more
rapid
decline.
Inflammatory
mechanisms,
including
cell
adhesion,
neutrophil
migration,
lipid
metabolism,
angiogenesis
may
be
implicated.
Physiological Reviews,
Journal Year:
2018,
Volume and Issue:
99(1), P. 21 - 78
Published: Oct. 3, 2018
The
blood-brain
barrier
(BBB)
prevents
neurotoxic
plasma
components,
blood
cells,
and
pathogens
from
entering
the
brain.
At
same
time,
BBB
regulates
transport
of
molecules
into
out
central
nervous
system
(CNS),
which
maintains
tightly
controlled
chemical
composition
neuronal
milieu
that
is
required
for
proper
functioning.
In
this
review,
we
first
examine
molecular
cellular
mechanisms
underlying
establishment
BBB.
Then,
focus
on
physiology,
endothelial
pericyte
transporters,
perivascular
paravascular
transport.
Next,
discuss
rare
human
monogenic
neurological
disorders
with
primary
genetic
defect
in
BBB-associated
cells
demonstrating
link
between
breakdown
neurodegeneration.
review
effects
genes
inheritance
and/or
increased
susceptibility
Alzheimer's
disease
(AD),
Parkinson's
(PD),
Huntington's
disease,
amyotrophic
lateral
sclerosis
(ALS)
relation
to
other
pathologies
deficits.
We
next
how
dysfunction
relates
deficits
majority
sporadic
AD,
PD,
ALS
cases,
multiple
sclerosis,
neurodegenerative
disorders,
acute
CNS
such
as
stroke,
traumatic
brain
injury,
spinal
cord
epilepsy.
Lastly,
BBB-based
therapeutic
opportunities.
conclude
lessons
learned
future
directions,
emphasis
technological
advances
investigate
functions
living
brain,
at
level,
address
key
unanswered
questions.
Biomaterials,
Journal Year:
2018,
Volume and Issue:
180, P. 117 - 129
Published: July 13, 2018
The
blood-brain
barrier
(BBB)
regulates
molecular
trafficking,
protects
against
pathogens,
and
prevents
efficient
drug
delivery
to
the
brain.
Models
date
failed
reproduce
human
anatomical
complexity
of
brain
barriers,
contributing
misleading
results
in
clinical
trials.
To
overcome
these
limitations,
a
novel
3-dimensional
BBB
microvascular
network
model
was
developed
via
vasculogenesis
accurately
replicate
vivo
neurovascular
organization.
This
microfluidic
system
includes
induced
pluripotent
stem
cell-derived
endothelial
cells,
pericytes,
astrocytes
as
self-assembled
vascular
networks
fibrin
gel.
Gene
expression
membrane
transporters,
tight
junction
extracellular
matrix
proteins,
consistent
with
computational
analysis
geometrical
structures
quantitative
immunocytochemistry,
indicating
maturation
microenvironment
remodelling.
Confocal
microscopy
validated
microvessel-pericyte/astrocyte
dynamic
contact-interactions.
exhibited
perfusable
selective
microvasculature,
permeability
lower
than
conventional
vitro
models,
similar
measurements
rat
robust
physiologically
relevant
offers
an
innovative
valuable
platform
for
discovery
predict
neuro-therapeutic
transport
efficacy
pre-clinical
applications
well
recapitulate
patient-specific
pathological
functions
neurodegenerative
disease.
