Cells,
Journal Year:
2018,
Volume and Issue:
7(4), P. 24 - 24
Published: March 23, 2018
The
blood–brain
barrier
(BBB)
is
a
critical
biological
structure
that
prevents
damage
to
the
brain
and
maintains
its
bathing
microenvironment.
However,
this
also
obstacle
deliver
beneficial
drugs
treat
CNS
(central
nervous
system)
diseases.
Many
efforts
have
been
made
for
improvement
of
delivering
across
BBB
in
recent
years
In
review,
anatomical
functional
comprehensively
discussed.
mechanisms
penetration
are
summarized,
methods
effects
on
increasing
permeability
investigated
detail.
It
elaborates
physical,
chemical,
nanocarrier
aspects
improve
drug
delivery
introduces
some
specific
permeability.
Fluids and Barriers of the CNS,
Journal Year:
2014,
Volume and Issue:
11(1), P. 10 - 10
Published: Jan. 1, 2014
According
to
the
traditional
understanding
of
cerebrospinal
fluid
(CSF)
physiology,
majority
CSF
is
produced
by
choroid
plexus,
circulates
through
ventricles,
cisterns,
and
subarachnoid
space
be
absorbed
into
blood
arachnoid
villi.
This
review
surveys
key
developments
leading
concept.
Challenging
this
concept
are
novel
insights
utilizing
molecular
cellular
biology
as
well
neuroimaging,
which
indicate
that
physiology
may
much
more
complex
than
previously
believed.
The
circulation
comprises
not
only
a
directed
flow
CSF,
but
in
addition
pulsatile
fro
movement
throughout
entire
brain
with
local
exchange
between
blood,
interstitial
fluid,
CSF.
Astrocytes,
aquaporins,
other
membrane
transporters
elements
water
homeostasis.
A
continuous
bidirectional
at
barrier
produces
rates,
exceed
choroidal
production
rate
far.
around
vessels
penetrating
from
Virchow
Robin
spaces
provides
both
drainage
pathway
for
clearance
waste
molecules
site
interaction
systemic
immune
system
brain.
Important
physiological
functions,
example
regeneration
during
sleep,
depend
on
circulation.
Pharmacological Reviews,
Journal Year:
2020,
Volume and Issue:
72(3), P. 606 - 638
Published: June 15, 2020
Epilepsy
is
a
chronic
neurologic
disorder
that
affects
over
70
million
people
worldwide.
Despite
the
availability
of
20
antiseizure
drugs
(ASDs)
for
symptomatic
treatment
epileptic
seizures,
about
one-third
patients
with
epilepsy
have
seizures
refractory
to
pharmacotherapy.
Patients
such
drug-resistant
(DRE)
increased
risks
premature
death,
injuries,
psychosocial
dysfunction,
and
reduced
quality
life,
so
development
more
effective
therapies
an
urgent
clinical
need.
However,
various
types
complex
temporal
patterns
refractoriness
complicate
issue.
Furthermore,
underlying
mechanisms
DRE
are
not
fully
understood,
though
recent
work
has
begun
shape
our
understanding
clearly.
Experimental
models
offer
opportunities
discover,
characterize,
challenge
putative
drug
resistance.
preclinical
important
in
developing
may
overcome
Here,
we
will
review
current
molecular,
genetic,
structural
ASD
resistance
discuss
how
this
problem.
Encouragingly,
better
elucidation
pathophysiological
underpinning
epilepsies
by
concerted
efforts
recently
enabled
revised
approach
promising
therapies,
including
numerous
potential
etiology-specific
("precision
medicine")
severe
pediatric
(monogenetic)
novel
multitargeted
ASDs
acquired
partial
epilepsies,
suggesting
long
hoped-for
breakthrough
therapy
as-yet
ASD-resistant
feasible
goal.
Significance
Statement
Drug
provides
major
management.
problem
might
be
overcome.
Signal Transduction and Targeted Therapy,
Journal Year:
2023,
Volume and Issue:
8(1)
Published: May 25, 2023
Abstract
Blood–brain
barrier
(BBB)
is
a
natural
protective
membrane
that
prevents
central
nervous
system
(CNS)
from
toxins
and
pathogens
in
blood.
However,
the
presence
of
BBB
complicates
pharmacotherapy
for
CNS
disorders
as
most
chemical
drugs
biopharmaceuticals
have
been
impeded
to
enter
brain.
Insufficient
drug
delivery
into
brain
leads
low
therapeutic
efficacy
well
aggravated
side
effects
due
accumulation
other
organs
tissues.
Recent
breakthrough
materials
science
nanotechnology
provides
library
advanced
with
customized
structure
property
serving
powerful
toolkit
targeted
delivery.
In-depth
research
field
anatomical
pathological
study
on
further
facilitates
development
brain-targeted
strategies
enhanced
crossing.
In
this
review,
physiological
different
cells
contributing
are
summarized.
Various
emerging
permeability
regulation
crossing
including
passive
transcytosis,
intranasal
administration,
ligands
conjugation,
coating,
stimuli-triggered
disruption,
overcome
obstacle
highlighted.
Versatile
systems
ranging
organic,
inorganic,
biologics-derived
their
synthesis
procedures
unique
physio-chemical
properties
summarized
analyzed.
This
review
aims
provide
an
up-to-date
comprehensive
guideline
researchers
diverse
fields,
offering
perspectives
system.
Fluids and Barriers of the CNS,
Journal Year:
2014,
Volume and Issue:
11(1), P. 26 - 26
Published: Jan. 1, 2014
Interstitial
fluid
(ISF)
surrounds
the
parenchymal
cells
of
brain
and
spinal
cord
while
cerebrospinal
(CSF)
fills
larger
spaces
within
around
CNS.
Regulation
composition
volume
these
fluids
is
important
for
effective
functioning
achieved
by
barriers
that
prevent
free
exchange
between
CNS
blood
mechanisms
secrete
controlled
into
distribute
reabsorb
it.
Structures
associated
with
this
regular
turnover
include
choroid
plexuses,
capillaries
comprising
blood-brain
barrier,
arachnoid
villi
perineural
penetrating
cribriform
plate.
ISF
flow,
estimated
from
rates
removal
markers
brain,
has
been
thought
to
reflect
secretion
across
although
questioned
because
measurements
were
made
under
barbiturate
anaesthesia
possibly
affecting
flow
CSF
influx
parenchyma
via
perivascular
routes
may
deliver
independently
barrier
secretion.
Fluid
at
provided
specific
transporters
generate
solute
fluxes
so
creating
osmotic
gradients
force
water
follow.
Any
due
hydrostatic
pressures
driving
soon
ceases
unless
accompanied
transport
movements
modify
concentrations.
be
derived
primarily
plexuses.
Flow
measured
using
phase
contrast
magnetic
resonance
imaging
reveal
more
rapid
variable
than
previously
supposed,
even
implying
some
circumstances
net
through
cerebral
aqueduct
reversed
third
lateral
ventricles.
Such
requires
there
alternative
sites
both
generation
CSF.
Fluorescent
tracer
analysis
shown
can
occur
along
periarterial
spaces.
Whether
represents
whether
subsequent
interstitium
out
cortex
perivenous
routes,
described
as
glymphatic
circulation,
remains
established.
Modern
techniques
have
revealed
complex
brain.
This
review
provides
a
critical
evaluation
data.
Advanced Materials,
Journal Year:
2018,
Volume and Issue:
30(46)
Published: July 31, 2018
Abstract
Therapies
directed
toward
the
central
nervous
system
remain
difficult
to
translate
into
improved
clinical
outcomes.
This
is
largely
due
blood–brain
barrier
(BBB),
arguably
most
tightly
regulated
interface
in
human
body,
which
routinely
excludes
therapeutics.
Advances
engineering
of
nanomaterials
and
their
application
biomedicine
(i.e.,
nanomedicine)
are
enabling
new
strategies
that
have
potential
help
improve
our
understanding
treatment
neurological
diseases.
Herein,
various
mechanisms
by
therapeutics
can
be
delivered
brain
examined
key
challenges
facing
translation
this
research
from
benchtop
bedside
highlighted.
Following
a
contextual
overview
BBB
anatomy
physiology
both
healthy
diseased
states,
relevant
therapeutic
for
bypassing
crossing
discussed.
The
focus
here
especially
on
nanomaterial‐based
drug
delivery
systems
these
overcome
biological
imposed
BBB.
Finally,
disease‐targeting
clearance
explored.
objective
provide
diverse
range
researchers
active
field
(e.g.,
material
scientists,
chemists,
engineers,
neuroscientists,
clinicians)
with
an
easily
accessible
guide
opportunities
currently
nanomaterial‐mediated
Acta Neuropathologica,
Journal Year:
2018,
Volume and Issue:
135(3), P. 387 - 407
Published: Feb. 10, 2018
Brain
fluids
are
rigidly
regulated
to
provide
stable
environments
for
neuronal
function,
e.g.,
low
K+,
Ca2+,
and
protein
optimise
signalling
minimise
neurotoxicity.
At
the
same
time,
astroglial
waste
must
be
promptly
removed.
The
interstitial
fluid
(ISF)
of
brain
tissue
cerebrospinal
(CSF)
bathing
CNS
integral
this
homeostasis
idea
a
glia-lymph
or
'glymphatic'
system
clearance
from
has
developed
over
last
5
years.
This
links
bulk
(convective)
flow
CSF
into
along
outside
penetrating
arteries,
glia-mediated
convective
transport
solutes
through
extracellular
space
(ECS)
involving
aquaporin-4
(AQP4)
water
channel,
finally
delivery
venules
peri-venous
spaces.
However,
recent
evidence
favours
important
amendments
hypothesis,
particularly
concerning
role
glia
transfer
within
ECS.
review
discusses
studies
which
question
AQP4
in
ISF
lack
its
ability
solutes;
summarizes
attributes
ECS
that
strongly
favour
diffusion
small
large
molecules
without
flow;
work
on
hydraulic
conductivity
nature
matrix
may
impede
movement;
reconsiders
roles
perivascular
(PVS)
CSF-ISF
exchange
drainage.
We
also
consider
extent
is
possible
desirable,
impact
neuropathology
drainage,
why
using
as
proxy
measure
components
drug
problematic.
propose
new
key
historical
both
support
concept
system,
whereby
enters
via
PVS
dispersion
larger
caliber
arteries/arterioles,
predominantly
regulates
CSF/ISF
at
level
neurovascular
unit
associated
with
microvessels,
and,
finally,
mixture
CSF/ISF/waste
products
normally
cleared
venules/veins
well
other
pathways;
such
not
constitute
true
'circulation',
but,
least,
suggests
comprehensive
re-evaluation
previously
proposed
concepts
better
taking
account
basic
cerebrovascular
physiology
considerations.
AJP Cell Physiology,
Journal Year:
2018,
Volume and Issue:
315(3), P. C343 - C356
Published: June 27, 2018
The
blood-brain
barrier
(BBB)
is
a
physical
and
biochemical
that
precisely
controls
cerebral
homeostasis.
It
also
plays
central
role
in
the
regulation
of
blood-to-brain
flux
endogenous
exogenous
xenobiotics
associated
metabolites.
This
accomplished
by
molecular
characteristics
brain
microvessel
endothelial
cells
such
as
tight
junction
protein
complexes
functional
expression
influx
efflux
transporters.
One
pathophysiological
features
ischemic
stroke
disruption
BBB,
which
significantly
contributes
to
development
injury
subsequent
neurological
impairment.
Biochemical
BBB
damage
include
decreased
altered
organization
constituent
proteins
well
modulation
Therefore,
there
critical
need
for
novel
therapeutic
strategies
can
protect
against
dysfunction
(i.e.,
vascular
protection)
setting
stroke.
Such
targeting
junctions
ensure
they
maintain
their
correct
structure
or
transporters
control
physiological
substrates
protection
In
this
review,
we
will
describe
mechanisms
microvascular
lead
following
onset
Additionally,
utilize
state-of-the-art
knowledge
provide
insights
on
pharmacological
be
developed
confer
