International Journal of Molecular Sciences,
Journal Year:
2023,
Volume and Issue:
24(16), P. 12699 - 12699
Published: Aug. 11, 2023
The
blood-brain
barrier,
which
is
formed
by
tightly
interconnected
microvascular
endothelial
cells,
separates
the
brain
from
peripheral
circulation.
Together
with
other
central
nervous
system-resident
cell
types,
including
pericytes
and
astrocytes,
barrier
forms
neurovascular
unit.
Upon
neuroinflammation,
this
becomes
leaky,
allowing
molecules
cells
to
enter
potentially
harm
tissue
of
system.
Despite
significance
animal
models
in
research,
they
may
not
always
adequately
reflect
human
pathophysiology.
Therefore,
are
needed.
This
review
will
provide
an
overview
terms
both
health
disease.
It
describe
all
key
elements
vitro
explore
how
different
compositions
can
be
utilized
effectively
model
a
variety
neuroinflammatory
conditions.
Furthermore,
it
existing
types
that
used
basic
research
study
respective
pathologies
thus
far.
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.
Frontiers in Physiology,
Journal Year:
2020,
Volume and Issue:
11
Published: Aug. 6, 2020
The
blood-brain
barrier
(BBB)
allows
the
brain
to
selectively
import
nutrients
and
energy
critical
neuronal
function
while
simultaneously
excluding
neurotoxic
substances
from
peripheral
circulation.
In
contrast
highly
permeable
vasculature
present
in
most
organs
that
reside
outside
of
central
nervous
system
(CNS),
BBB
exhibits
a
high
transendothelial
electrical
resistance
along
with
low
rate
transcytosis
greatly
restricted
paracellular
permeability.
property
permeability
is
controlled
by
tight
junction
protein
complexes
seal
route
between
apposing
microvascular
endothelial
cells.
Although
are
principal
contributors
physical
properties,
they
not
static
nature.
Rather,
dynamic
structures
where
expression
and/or
localization
individual
constituent
proteins
can
be
modified
response
pathophysiological
stressors.
These
stressors
induce
modifications
involve
de
novo
synthesis
new
or
discrete
trafficking
mechanisms.
Such
responsiveness
junctions
diseases
indicates
these
for
maintenance
CNS
homeostasis.
fulfillment
this
vital
role,
also
major
obstacle
therapeutic
drug
delivery
brain.
There
an
opportunity
overcome
substantial
optimize
neuropharmacology
via
acquisition
detailed
understanding
structure,
function,
regulation.
review,
we
discuss
physiological
characteristics
how
properties
regulate
therapeutics
treatment
neurological
diseases.
Specifically,
will
modulation
regulation
both
context
disease
states
setting
pharmacotherapy.
particular,
highlight
potentially
manipulated
at
molecular
level
increase
levels
transport
CNS Drugs,
Journal Year:
2021,
Volume and Issue:
35(9), P. 935 - 963
Published: June 18, 2021
Epilepsy
is
one
of
the
most
common
and
disabling
chronic
neurological
disorders.
Antiseizure
medications
(ASMs),
previously
referred
to
as
anticonvulsant
or
antiepileptic
drugs,
are
mainstay
symptomatic
epilepsy
treatment.
a
multifaceted
complex
disease
so
its
Currently,
about
30
ASMs
available
for
therapy.
Furthermore,
several
approved
therapies
in
nonepileptic
conditions,
including
neuropathic
pain,
migraine,
bipolar
disorder,
generalized
anxiety
disorder.
Because
this
wide
spectrum
therapeutic
activity,
among
often
prescribed
centrally
active
agents.
Most
act
by
modulation
voltage-gated
ion
channels;
enhancement
gamma
aminobutyric
acid-mediated
inhibition;
through
interactions
with
elements
synaptic
release
machinery;
blockade
ionotropic
glutamate
receptors;
combinations
these
mechanisms.
differences
their
mechanisms
action,
do
not
suppress
all
types
seizures,
appropriate
treatment
choices
important.
The
goal
therapy
complete
elimination
seizures;
however,
achievable
one-third
patients.
Both
vivo
vitro
models
seizures
used
discover
that
more
effective
patients
continued
drug-resistant
seizures.
specific
etiology
being
developed.
~
new
compounds
diverse
antiseizure
preclinical
clinical
drug
development
pipeline.
Moreover,
potential
antiepileptogenic
disease-modifying
effects
development.
Overall,
world
changing
evolving
many
exciting
important
ways.
However,
while
developed,
knowledge
pharmacokinetics,
efficacy
spectrum,
adverse
effect
profiles
currently
an
essential
component
treating
successfully
maintaining
high
quality
life
every
patient,
particularly
those
receiving
polypharmacy
Cells,
Journal Year:
2020,
Volume and Issue:
9(11), P. 2360 - 2360
Published: Oct. 27, 2020
Severe
acute
respiratory
syndrome
coronavirus
2
(SARS-CoV-2)
is
a
novel
human
that
has
sparked
global
pandemic
of
the
disease
2019
(COVID-19).
The
virus
invades
cells
through
angiotensin-converting
enzyme
(ACE2)
receptor-driven
pathway,
primarily
targeting
tract.
However,
emerging
reports
neurological
manifestations
demonstrate
neuroinvasive
potential
SARS-CoV-2.
This
review
highlights
possible
routes
by
which
SARS-CoV-2
may
invade
central
nervous
system
(CNS)
and
provides
insight
into
recent
case
COVID-19-associated
disorders,
namely
ischaemic
stroke,
encephalitis,
encephalopathy,
epilepsy,
neurodegenerative
diseases,
inflammatory-mediated
disorders.
We
hypothesize
neuroinvasion,
neuroinflammation,
blood-brain
barrier
(BBB)
dysfunction
be
implicated
in
development
observed
disorders;
however,
further
research
critical
to
understand
detailed
mechanisms
pathway
infectivity
behind
CNS
pathogenesis.
Nature Communications,
Journal Year:
2022,
Volume and Issue:
13(1)
Published: April 14, 2022
Abstract
Blood-brain
barrier
(BBB)
dysfunction
is
associated
with
worse
epilepsy
outcomes
however
the
underlying
molecular
mechanisms
of
BBB
remain
to
be
elucidated.
Tight
junction
proteins
are
important
regulators
integrity
and
in
particular,
tight
protein
claudin-5
most
enriched
brain
endothelial
cells
regulates
size-selectivity
at
BBB.
Additionally,
disruption
expression
has
been
implicated
numerous
disorders
including
schizophrenia,
depression
traumatic
injury,
yet
its
role
not
fully
deciphered.
Here
we
report
that
levels
significantly
diminished
surgically
resected
tissue
from
patients
treatment-resistant
epilepsy.
Concomitantly,
dynamic
contrast-enhanced
MRI
these
showed
widespread
disruption.
We
show
targeted
hippocampus
or
genetic
heterozygosity
mice
exacerbates
kainic
acid-induced
seizures
inducible
knockdown
leads
spontaneous
recurrent
seizures,
severe
neuroinflammation,
mortality.
Finally,
identify
RepSox,
a
regulator
expression,
can
prevent
seizure
activity
experimental
Altogether,
propose
stabilizing
drugs
could
represent
new
generation
agents
patients.
Brain Sciences,
Journal Year:
2023,
Volume and Issue:
13(5), P. 784 - 784
Published: May 11, 2023
Epilepsy
is
a
central
nervous
system
disorder
involving
spontaneous
and
recurring
seizures
that
affects
50
million
individuals
globally.
Because
approximately
one-third
of
patients
with
epilepsy
do
not
respond
to
drug
therapy,
the
development
new
therapeutic
strategies
against
could
be
beneficial.
Oxidative
stress
mitochondrial
dysfunction
are
frequently
observed
in
epilepsy.
Additionally,
neuroinflammation
increasingly
understood
contribute
pathogenesis
Mitochondrial
also
recognized
for
its
contributions
neuronal
excitability
apoptosis,
which
can
lead
loss
This
review
focuses
on
roles
oxidative
damage,
dysfunction,
NAPDH
oxidase,
blood–brain
barrier,
excitotoxicity,
We
therapies
used
treat
prevent
seizures,
including
anti-seizure
medications,
anti-epileptic
drugs,
anti-inflammatory
therapies,
antioxidant
therapies.
In
addition,
we
use
neuromodulation
surgery
treatment
Finally,
present
role
dietary
nutritional
management
epilepsy,
ketogenic
diet
intake
vitamins,
polyphenols,
flavonoids.
By
reviewing
available
interventions
research
pathophysiology
this
points
areas
further
manage
