Translational Neurodegeneration,
Journal Year:
2021,
Volume and Issue:
10(1)
Published: Nov. 5, 2021
Abstract
Background
Focused
ultrasound
(FUS)-mediated
blood–brain
barrier
(BBB)
opening
has
shown
efficacy
in
removal
of
amyloid
plaque
and
improvement
cognitive
functions
preclinical
studies,
but
this
is
rarely
reported
clinical
studies.
This
study
was
conducted
to
evaluate
the
safety,
feasibility
potential
benefits
repeated
extensive
BBB
opening.
Methods
In
open-label,
prospective
study,
six
patients
with
Alzheimer’s
disease
(AD)
were
enrolled
at
Severance
Hospital
Korea
between
August
2020
September
2020.
Five
them
completed
study.
FUS-mediated
opening,
targeting
bilateral
frontal
lobe
regions
over
20
cm
3
,
performed
twice
three-month
intervals.
Magnetic
resonance
imaging,
18
F-Florbetaben
(FBB)
positron
emission
tomography,
Caregiver-Administered
Neuropsychiatric
Inventory
(CGA-NPI)
comprehensive
neuropsychological
tests
before
after
procedures.
Results
FUS
targeted
a
mean
volume
21.1
±
2.7
confirmed
95.7%
9.4%
volume.
The
frontal-to-other
cortical
region
FBB
standardized
uptake
value
ratio
months
procedure
showed
slight
decrease,
which
statistically
significant,
compared
pre-procedure
(−
1.6%,
0.986
vs
1.002,
P
=
0.043).
CGA-NPI
score
2
weeks
second
significantly
decreased
baseline
(2.2
3.0
8.6
6.0,
0.042),
recovered
(5.2
5.8
0.89).
No
adverse
effects
observed.
Conclusions
safe
feasible
for
AD.
addition,
potentially
beneficial
AD
patients.
Science,
Journal Year:
2022,
Volume and Issue:
377(6607), P. 751 - 755
Published: Aug. 11, 2022
Tough
bioadhesion
has
important
implications
in
engineering
and
medicine
but
remains
challenging
to
form
control.
We
report
an
ultrasound
(US)-mediated
strategy
achieve
tough
with
controllability
fatigue
resistance.
Without
chemical
reaction,
the
US
can
amplify
adhesion
energy
interfacial
threshold
between
hydrogels
porcine
skin
by
up
100
10
times.
Combined
experiments
theoretical
modeling
suggest
that
key
mechanism
is
US-induced
cavitation,
which
propels
immobilizes
anchoring
primers
into
tissues
mitigated
barrier
effects.
Our
achieves
spatial
patterning
of
bioadhesion,
on-demand
detachment,
transdermal
drug
delivery.
This
work
expands
material
repertoire
for
enables
bioadhesive
technologies
high-level
controllability.
Advanced Science,
Journal Year:
2021,
Volume and Issue:
8(16)
Published: June 3, 2021
Abstract
The
blood–brain
barrier
(BBB)
is
a
highly
specialized
neurovascular
unit,
initially
described
as
an
intact
to
prevent
toxins,
pathogens,
and
potentially
harmful
substances
from
entering
the
brain.
An
BBB
also
critical
for
maintenance
of
normal
neuronal
function.
In
cerebral
vascular
diseases
neurological
disorders,
can
be
disrupted,
contributing
disease
progression.
While
restoration
integrity
serves
robust
biomarker
better
clinical
outcomes,
restrictive
nature
presents
major
hurdle
delivery
therapeutics
into
Recent
studies
show
that
actively
engaged
in
crosstalk
between
circulatory
systems,
which
defines
another
important
role
BBB:
interfacing
conduit
mediates
communication
two
sides
BBB.
This
has
been
subject
extensive
investigation
brain‐targeted
drug
shows
promising
results.
dual
roles
make
it
unique
target
development.
Here,
recent
developments
novel
strategies
therapeutic
purposes
are
reviewed,
both
carrier
perspectives.
Advanced Science,
Journal Year:
2022,
Volume and Issue:
9(17)
Published: May 4, 2022
Glioblastoma
(GBM)
is
one
of
the
most
fatal
central
nervous
system
tumors
and
lacks
effective
or
sufficient
therapies.
Ferroptosis
a
newly
discovered
method
programmed
cell
death
opens
new
direction
for
GBM
treatment.
However,
poor
blood-brain
barrier
(BBB)
penetration,
reduced
tumor
targeting
ability,
potential
compensatory
mechanisms
hinder
effectiveness
ferroptosis
agents
during
Here,
novel
composite
therapeutic
platform
combining
magnetic
features
drug
delivery
properties
nanoparticles
with
BBB
penetration
abilities
siRNA
encapsulation
engineered
exosomes
therapy
presented.
This
can
be
enriched
in
brain
under
local
localization
angiopep-2
peptide-modified
trigger
transcytosis,
allowing
particles
to
cross
target
cells
by
recognizing
LRP-1
receptor.
Synergistic
achieved
combined
triple
actions
disintegration
dihydroorotate
dehydrogenase
glutathione
peroxidase
4
defense
axis
Fe
New England Journal of Medicine,
Journal Year:
2024,
Volume and Issue:
390(1), P. 55 - 62
Published: Jan. 3, 2024
Antiamyloid
antibodies
have
been
used
to
reduce
cerebral
amyloid-beta
(Aβ)
load
in
patients
with
Alzheimer's
disease.
We
applied
focused
ultrasound
each
of
six
monthly
aducanumab
infusions
temporarily
open
the
blood-brain
barrier
goal
enhancing
amyloid
removal
selected
brain
regions
three
participants
over
a
period
6
months.
The
reduction
level
Aβ
was
numerically
greater
treated
than
homologous
contralateral
hemisphere
that
were
not
ultrasound,
as
measured
by
fluorine-18
florbetaben
positron-emission
tomography.
Cognitive
tests
and
safety
evaluations
conducted
30
180
days
after
treatment.
(Funded
Harry
T.
Mangurian,
Jr.
Foundation
West
Virginia
University
Rockefeller
Neuroscience
Institute.).
Neuropathology and Applied Neurobiology,
Journal Year:
2021,
Volume and Issue:
48(3)
Published: Nov. 26, 2021
Abstract
The
pathological
processes
leading
to
synapse
loss,
neuronal
brain
atrophy
and
gliosis
in
Alzheimer's
disease
(AD)
their
relation
vascular
immunological
changes
are
yet
be
fully
explored.
Amyloid‐β
(Aβ)
aggregation,
damage
altered
immune
response
interact
at
the
blood–brain
barrier
(BBB),
affecting
endothelium
fuelling
neurodegeneration.
aim
of
present
systematic
literature
review
was
critically
appraise
summarise
published
evidence
on
clinical
correlations
pathophysiological
concepts
BBB
AD,
focusing
human
data.
PubMed,
Cochrane,
Medline
Embase
databases
were
searched
for
original
research
articles,
reviews
meta‐analyses,
English
language
from
01/2000
07/2021,
using
keywords
Alzheimer*,
amyloid‐β
or
β‐amyloid
abeta
BBB.
This
shows
that
specific
intercellular
structures,
reduced
expression
transendothelial
carriers,
induction
vasoactive
mediators
activation
both
astroglia
monocytes/macrophages
characterise
AD
models.
dysfunction
magnetic
resonance
imaging
takes
place
early
course
AD‐specific
regions.
toxic
effects
Aβ
apolipoprotein
E
(ApoE)
likely
induce
a
non‐cerebral‐amyloid‐angiopathy‐related
degeneration
endothelial
cells,
independently
cerebrovascular
disease;
however,
some
observed
structural
may
just
arise
with
age.
Small
vessel
disease,
ApoE,
loss
pericytes,
proinflammatory
signalling
cerebral
amyloid
angiopathy
enhance
damage.
Novel
therapeutic
approaches
including
resonance‐guided
focused
ultrasound,
open
BBB,
potentially
an
improved
drainage
along
perivascular
channels
increased
elimination
brain.
In
vitro
treatments
ApoE‐modifying
agents
yielded
promising
modulating
function.
Reducing
cardiovascular
risk
factors
represents
one
most
interventions
dementia
prevention
present.
However,
further
is
needed
elucidate
connection
tau
pathology,
role
draining
macromolecules
cells
parenchyma,
contribution
angiopathy.
Improved
insight
into
these
pathomechanisms
allow
shed
light
deposition
as
primary
versus
secondary
event
complex
pathogenesis
AD.
