Cell Death and Disease,
Journal Year:
2013,
Volume and Issue:
4(7), P. e734 - e734
Published: July 18, 2013
The
use
of
the
visual
system
played
a
major
role
in
elucidation
molecular
mechanisms
controlling
axonal
regeneration
injured
CNS
after
trauma.
In
this
model,
CNTF
was
shown
to
be
most
potent
known
neurotrophic
factor
for
optic
nerve.
To
clarify
downstream
growth
regulator
Stat3,
we
analyzed
and
neuronal
survival
an
nerve
crush
adult
mice.
infection
retinal
ganglion
cells
with
adeno-associated
virus
serotype
2
(AAV2)
containing
wild-type
(Stat3-wt)
or
constitutively
active
(Stat3-ca)
Stat3
cDNA
promoted
Axonal
whole-mounted
nerves
three
dimensions
(3D)
tissue
clearing.
Surprisingly,
AAV2.Stat3-ca
stimulation,
axons
elongating
beyond
lesion
site
displayed
very
irregular
courses,
including
frequent
U-turns,
suggesting
massive
directionality
guidance
problems.
pharmacological
blockade
ROCK,
key
signaling
component
myelin-associated
inhibitors,
reduced
U-turns
potentiated
AAV2.Stat3-ca-induced
regeneration.
Similar
results
were
obtained
sustained
delivery
axotomized
retina.
These
show
important
activation
program
regeneration,
they
reveal
that
misguidance
is
limiting
can
affect
long-distance
target
interaction
trauma
CNS.
correction
associated
improved
axon
Disease Models & Mechanisms,
Journal Year:
2016,
Volume and Issue:
9(10), P. 1125 - 1137
Published: Oct. 1, 2016
ABSTRACT
A
long-standing
goal
of
spinal
cord
injury
research
is
to
develop
effective
repair
strategies
for
the
clinic.
Rat
models
provide
an
important
mammalian
model
in
which
evaluate
treatment
and
understand
pathological
basis
injuries.
These
have
facilitated
development
robust
tests
assessing
recovery
locomotor
sensory
functions.
also
allowed
us
how
neuronal
circuitry
changes
following
could
be
promoted
by
enhancing
spontaneous
regenerative
mechanisms
counteracting
intrinsic
inhibitory
factors.
studies
revealed
possible
routes
rescuing
cells
acute
stage
injury.
Spatiotemporal
functional
these
highlight
therapeutic
potential
manipulating
inflammation,
scarring
myelination.
In
addition,
replacement
therapies
injury,
including
grafts
bridges,
stem
primarily
from
rat
studies.
Here,
we
discuss
advantages
disadvantages
experimental
summarize
knowledge
gained
models.
We
emerging
understanding
different
forms
their
pathology
degree
has
inspired
numerous
strategies,
some
led
clinical
trials.
Cold Spring Harbor Perspectives in Biology,
Journal Year:
2014,
Volume and Issue:
7(3), P. a020602 - a020602
Published: Dec. 4, 2014
Jerry
Silver1,
Martin
E.
Schwab2
and
Phillip
G.
Popovich3
1Department
of
Neurosciences,
Case
Western
Reserve
University,
Cleveland,
Ohio
44140
2Brain
Research
Institute,
University
Zurich
Department
Health
Sciences
Technology,
ETH
Zurich,
8057
Switzerland
3Center
for
Brain
Spinal
Cord
Repair,
State
Columbus,
43210
Correspondence:
phillip.popovich{at}osumc.edu
ALTEX,
Journal Year:
2016,
Volume and Issue:
unknown, P. 362 - 376
Published: Nov. 24, 2016
Human
in
vitro
models
of
brain
neurophysiology
are
needed
to
investigate
molecular
and
cellular
mechanisms
associated
with
neurological
disorders
neurotoxicity.
We
have
developed
a
reproducible
iPSC-derived
human
3D
microphysiological
system
(BMPS),
comprised
differentiated
mature
neurons
glial
cells
(astrocytes
oligodendrocytes)
that
reproduce
neuronal-glial
interactions
connectivity.
BMPS
over
eight
weeks
show
the
critical
elements
neuronal
function:
synaptogenesis
neuron-to-neuron
(e.g.,
spontaneous
electric
field
potentials)
myelination),
which
mimic
microenvironment
central
nervous
system,
rarely
seen
before.
The
shows
40%
overall
myelination
after
8
differentiation.
Myelin
was
observed
by
immunohistochemistry
confirmed
confocal
microscopy
reconstruction
electron
microscopy.
These
findings
particular
relevance
since
myelin
is
crucial
for
proper
function
development.
ability
assess
oligodendroglial
this
model
provide
an
excellent
tool
future
studies
such
as
multiple
sclerosis
other
demyelinating
diseases.
provides
suitable
reliable
neuron-neuroglia
well
pathogenic
neurotoxicology.
Bone Research,
Journal Year:
2022,
Volume and Issue:
10(1)
Published: April 8, 2022
Spinal
cord
injury
(SCI)
leads
to
loss
of
motor
and
sensory
function
below
the
level
imposes
a
considerable
burden
on
patients,
families,
society.
Repair
injured
spinal
has
been
recognized
as
global
medical
challenge
for
many
years.
Significant
progress
made
in
research
pathological
mechanism
injury.
In
particular,
with
development
gene
regulation,
cell
sequencing,
tracing
technologies,
in-depth
explorations
SCI
microenvironment
have
become
more
feasible.
However,
translational
studies
related
repair
not
yielded
significant
results.
This
review
summarizes
latest
two
aspects
pathology:
intraneuronal
imbalance
regenerative
imbalance.
We
also
strategies
based
imbalance,
including
medications,
transplantation,
exosomes,
tissue
engineering,
reprogramming,
rehabilitation.
The
current
state
future
directions
are
discussed.
combined,
precise,
multitemporal
strategy
repairing
is
potential
direction.