Neurogenesis

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Oct 20, 2013 (3 years and 5 months ago)

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Brain destruction:

Are
porencephaly
, cystic
encepha
-
lomalacia
,
leukoencephalomalacia

and gliosis synonyms?

Jorge Davila
MD
1,2
, Dahlia Hassan MD
1
,
2
, Margarita Beltran
-
Marin MD
3
, and
Elka Miller
MD
1,2

1
Children’s Hospital of Eastern Ontario,
2
University
of
Ottawa, Ontario, Canada,
3
Erasme University Hospital, Brussels, Belgium.

eEdE

149

NO DISCLOSURES


Brain destruction is highly polymorphic. Different causes may
lead to brain destruction by different pathways with a common
morphologic appearance.



The appearance,
location and degree of brain damage,
depends on duration and severity of the causative event but
mainly is related to the state of brain development and
maturation.



The
selectiveness of brain damage depends also on the
vulnerability of the different cell types during the development
of the
brain including: neurogenesis,
oligodendrogenesis

and
astrogenesis
.

INTRODUCTION

What is your diagnosis
?


Brain development is a dynamic process, and although neurons are
detected in the subcortex as early as 10 weeks GA, neuronal proliferation
carries on throughout the second trimester and maturation continues
beyond term


There is a linear increase in brain volume with gestational age (GA)









Significant increase in dendritic connections and sulci formation occur
during the last 5 weeks of gestation

Brain maturation

GA

(weeks)

Brain weight as % of full

term brain weight

20

10%

32

50%

36

80%

38

90%

40

100%

Adams
-
Chapman I. (2009) Insults to the developing brain and impact on neurodevelopmental outcome.
Journal of Communication Disorders ,
42, 256
-
262


Preoligodendroglia

(OPCs) are the precursors to the
developing brain white matter. These cells comprise the
dominant cell linage in the developing white matter between
28


41 weeks GA.



These OPCs are uniquely vulnerable to injury, especially in
infants born prematurely.



Other critical phases of brain maturation and development;
namely Axonal synaptogenesis, Maturation & Elongation, also
occur during the latter half of gestation

Brain maturation

Adams
-
Chapman I. (2009) Insults to the developing brain and impact on neurodevelopmental outcome.
Journal of Communication Disorders ,
42,
256
-
262

Types of
astrocytic

stem cells

From: Silver D, Steindler D, Common
astrocytic

programs
during brain development, injury and cancer.
Trends in
Neurosciences;
32:6, 303
-
11

a)
Developmental boundary astrocytes
: Present in the somatosensory cortical whisker
barrel system during early postnatal development

b)
Adult
neurogenic
astrocytes:
Neural Stem Cells (NSCs)
present
in
the
subventricular

zone
(SVZ) around the
lateral ventricles (LV) and
in the
hippocampus. Characteristics: self
-
renewal
,
neurosphere

generation
and
ability to
give rise to
all three neural lineages:
O
ligodendrocytes

(OLs);
N
eurons (Ns);
and A
strocytes (ASs)

c)
Cytogenic

reactive astrocytes:

Injury
-
related astrocytes that attempt
reactive
neurogenesis
after a brain injury. Similar NSCs characteristics

d)
Tumorigenic astrocytes:
Give
rise to the tumor mass
and
contribute to invasion and
metastasis

OLs

Ns

ASs


The CNS has a limited regenerative capacity even though NSCs are
present in the CNS throughout adult life.


Astrocytes are the most abundant cells in the CNS and are involved
in several pathologies like trauma, ischemia and neurodegenerative
diseases.


In the normal brain, astrocytes are usually found in a non
-
reactive
status and the intermediate filament (IF) network is composed of

proteins glial
fibrillary

acidic protein (GFAP)

&
vimentin
.


Injury to the CNS


Reactive astrocytes (hypertrophy of their
cellular processes and upregulation of the
GFAP
& vimentin and
expression of IF nestin & synemin)


This process is known as
Reactive Gliosis.

Astrocytes and their role in
CNS injury

Milos
Pekny
, Ulrika
Wilhelmsson

et al (2007). The role of astrocytes and complement system in neural plasticity. International Review
of Neurobiology , 82: 95
-
111





Reactive astrocytes increase
the
thickness of
their main

cellular
processes but
occupy a volume of
tissue
comparable
to that
of
nonreactive

astrocytes.



Despite
the hypertrophy of
GFAP
-
containing cellular
processes,
the
interdigitation

between
adjacent reactive astrocytes
in
denervated

hippocampus
remains minimal.

Volumes of the reactive astrocytes remain similar to non reactive
astrocytes; however, there is thickness of the main cellular process making
them visible over a greater distance (gray circle)


From: Milos
Pekny
, Ulrika
Wilhelmsson

et al (2007). The role of astrocytes and
complement system in neural plasticity. International Review of Neurobiology ,
82: 95
-
111

Reactive gliosis


Reactive astrocytes have a two
-
fold effect following CNS
injury:

i.
Neuro
-
protective role in the early stages following
neurotrauma

ii.
At a later stage they
are
believed to:

1.
Lead
to formation of glial
scars

2.
Inhibit CNS regeneration

3.
Interfere with neural graft uptake and integration

4.
Interfere with synaptic regeneration

5.
Inhibit CNS regeneration in old age

6.
Inhibit regeneration of severed CNS axons

Astrocytes and their role in
CNS injury

Milos
Pekny
, Ulrika
Wilhelmsson

et al (2007). The role of astrocytes and complement system in neural plasticity. International Review of
Neurobiology , 82: 95
-
111


Glial
cells ensure proper development, function and repair of the
neuronal network through neurotransmitters, cytokines and
growth and tropic factor secretion reciprocally
.


Oligodendrocytes (OLs) are responsible for axon myelination, but
only if the OLs are mature and neuron growth is proper
.


Repair of the brain depends on
OLs:
the percentage of repair
depends on the developmental stage of the
OLs.


Neuron
-

glial network may be altered as a response to injury or
during the course of a neurological disease and the repair capacity
depends on mature
OLs.

Oligodendrocytes

and their role in
brain maturation

Butts BD,
Houde

C,
Memet

H. Maturation

dependent sensitivity of
oligodendrocyte

lineage cells to apoptosis: implications for normal development
and disease. Cell death and differentiation 2008:15;1178
-
1186


Undifferentiated

Differentiated

Stage 1
Oligodendrocytes

precursor cell (OPC)

Stage 2 Pro
-
oligodendrocytes

Stage 3,

immature
OLs

Stage 4,

mature OLs

Morphology

Bipolar cells

Branching
processes

Mature
arborization

Myelin

sheaths
around axons

Motility


Yes

No

Cell

division

Yes

No

Table 1: Characteristics of the four stages of OL differentiation


Antigenic profile varies in each stage of OLs.


Undifferentiated OLs ( which are more active during embryonic
and perinatal life), are more sensitive to oxidative stress and
glutamate
-
related
excitotoxicity
.


Interaction between OLs and neurons is necessary to pass from
undifferentiated stage to differentiated forms of OLs.


Butts BD,
Houde

C,
Memet

H. Maturation

dependent sensitivity of oligodendrocyte lineage cells to apoptosis: implications for normal
development and disease. Cell death and differentiation 2008:15;1178
-
1186

Oligodendrogenesis

Stages of
Oligodendrocyte

differentiation

From:
Kolodziejczyk

K, Saab AS,

Klaus
-
Armin Nave, et al. Why
do oligodendrocyte lineage cells express glutamate receptors
? F1000
Biol

Rep
.
2010; 2:
57


Undifferentiated OLs are the predominant cell type in white matter during
23
-
32 weeks of gestation. Selective death of these cells could severely
disrupt myelination in newborn infants since the pool of dividing cells with
OLs would be significantly depleted.


OPCs derive from the
neuroepithelium

of the periventricular region
(beginning of embryonic life) and from
subventricular

region (late
embrionic life and early postnatal).

Butts BD,
Houde

C,
Memet

H. Maturation

dependent sensitivity of oligodendrocyte lineage cells to apoptosis: implications for normal
development and disease. Cell death and differentiation 2008:15;1178
-
1186

Oligodendrogenesis

Pro OL

OPC

Inmature

OL

Mature OL


There are 2 areas that produce mature myelinating OLs in the adult
brain:

i.
Local OPCs in the brain parenchyma, which continuously produce OLs

ii.
NSCs in the SV zone


NSCs are an endogenous source of cells for brain repair. They are multi
-
potent cells that self
-
renew and differentiate into neurons, astrocytes
and OLs.


These NSCs are restricted to the specific areas in the adult brain, most
important of which is the Sub
-
Ventricular Zone (SVZ).


One important regulator of the activity of the NSCs is the epidermal
growth factor (EGF).


Overstimulation of EGF pathway leads to more NSCs differentiating into
OPCs.




Oligodendrogenesis

in the adult
brain

Oscar Gonzalez
-
Perez, Arturo Alvarez
-
Buyella

(2011). Oligodendrogenesis in the subventricular zone & the role of epidermal growth factor. Brain
Research reviews 67: 147
-
156


Neurogenesis: Formation of new neurons



Embryological neurogenesis (proliferation and differentiation)
occurs in 4 germinal matrices: a) medial
ganglionic eminence,
b) lateral
ganglionic eminence
c)
preoptic

area
(
IIIrd

ventricle)
and dorsal neocortical germinal zone (lateral ventricles) .



Neurogenesis in the mature brain: stem
cells
are present
in
2
areas: a)
subventricular

zone of the lateral ventricles
-
olfactory
bulb pathway and b) hippocampal dentate
gyrus
.



Brain insults induce neurogenesis and
astrocytic

gliosis, being
difficult to differentiate both of them, since
the markers are
similar, and
only a few
neurons will survive.

Neurogenesis

S.G.
Kernie
, J.M. Parent / Neurobiology of Disease 37 (2010) 267

274


It
is
well
established that hippocampal progenitors are
activated by injury and result in increased numbers of new
neurons within the dentate
gyrus
.


What is the outcome of injury
-
induced neurogenesis?

There
are three
possibilities:

1.
Neurogenesis might contribute
to recovery of
learning,
memory
and
other
functions impaired by brain
injury.

2.
Neurogenesis
may
be aberrant and may contribute
to TBI
-
related
or stroke
-
related morbidity such
as temporal lobe
epilepsy

3.
Neurogenesis may
be nothing more than a developmental
remnant (incapable
of providing
functionally)

Neurogenesis

S.G.
Kernie
, J.M. Parent / Neurobiology of Disease 37 (2010) 267

274


The
injured
brain releases
numerous extracellular proteins and
ions that
regulate neurogenesis.


KCl

and glutamate, both have been
implicated
in:

1.
Enhancement
of
proliferation in
immature
cells and at
the
same time

2.
Toxicity
in
more mature
cell types



The
progenitor
cells
make
physical contact with the
vasculature
so circulating cytokines
and growth
factors (that
increase after
injury) may
also direct some of these
effects


Neurogenesis

S.G.
Kernie
, J.M. Parent / Neurobiology of Disease 37 (2010) 267

274

Neurogenesis and
oligodendrogenesis

in
adult brain injury

Oscar Gonzalez
-
Perez, Arturo Alvarez
-
Buyella

(2011). Oligodendrogenesis in the subventricular zone & the role of epidermal growth factor. Brain
Research reviews 67: 147
-
156

NSCs in the SVZ

Actively
proliferating transit
-
amplifying cells
or
Type
-
C
cells

SVZ
-
derived
OPCs

(
migratory and
can participate in
remyelination

of white matter tracts)

Myelinating

oligodendrocytes

Immature
neuroblasts

or
Type
-
A cells

Distinct
Interneurons

(in
the olfactory bulb)

Slowly dividing
Type
-
B cells

“astrocyte neural progenitor”

Epidermal growth factor stimulation

(e.g. Demyelinating process)


Microglia are not

neuroglia
”, they are
histocytes

of the CNS
that interface with the
immune system.


Activation results
in morphologic transformation
to

“pleomorphic

microglia,

which
respond to low
grade,
incomplete
necrosis, or
chronic infections.


Activated microglia is
capable of ingesting
destroyed
nerve
cell
fragments (
neuronophagia
) or myelin.


Activation to
macrophages
occurs with
acute, severe
tissue
destruction, and with active
demyelination.


Reactive
macrophages in
brain
arise
from microglia and
from
circulating monocytes.

Role of
microglia in
brain
injury

Marie Rivera
-
Zengotita
, MD and Anthony T.
Yachnis
,
MD

Gliosis Versus
Glioma
?: Don’t Grade Until You
Know

Adv

Anat

Pathol

Volume 19,
Number 4, July 2012



Local
expression of complement in the CNS occurs in microglia,
astrocytes and neurons, and this increases following brain infection &
ischemia



Complement activation following CNS injury is believed to exacerbate
inflammatory response and lead to secondary tissue damage



Studies
on mice have
suggested
that complement may have a role as a
positive regulator of adult neurogenesis following
ischemia



It seems
that Complement activation in the CNS has a dual role,
functioning as a physiological neuro
-
protective mechanism, as well as
participating in maintenance and repair of the adult
CNS

Milos
Pekny
, Ulrika
Wilhelmsson

et al (2007). The role of astrocytes and complement system in neural plasticity. International Review of
Neurobiology , 82: 95
-
111

Role of complement system in
brain injury


The outcome of diffuse insults to the brain depends
on:


1.
Etiology

2.
Maturity of the brain cells at the time of insult

3.
Severity of the insult

Outcome of brain damage

Barkovich

A. J. & Schwartz E., Brain and Spine Injuries in Infancy and Childhood. Pediatric Neuroimaging. Chapter 4; 240
-
245


The immature brain’s response to injury has a different pattern
than that of the mature brain



The fetal brain
can only evoke a limited
astrocytic

response to
injury


injury at the end of second trimester or early third
trimester will lead to the formation of a fluid
-
filled smooth
-
walled cavity with little or no
perilesional

gliosis, upon
resorption

of the necrotic brain tissue



The mature
brain

responds by
a
significant
astrocytic

response, leading to the formation of a lesion that contains
soft brain tissue and is surrounded by reactive astrocytes
composing an irregular wall lining of the lesion

Outcome of brain damage

Low C. et al. Early destructive lesions in the developing brain. Clinical and electrographic correlates
Arq

Neuropsiquiatr

2007; 65 (2
-
B):
416
-
422


The neonatal and infant brains
fall somewhere in between the fetal and mature
brain, in the
astrocytic

response they evoke in response to injury, leading to the
formation of
cavities
with imprecise limits and surrounded by an
astroglial

reaction


The brain’s capacity to evoke an
astrocytic

response
starts somewhere around
the late second or early third trimester, and increases progressively with age


The neonatal brain has about 15% of the
astrocytic

response to injury as the
mature brain



Therefore, the post injury brain lesion ranges from:

1.
A simple cyst in the second trimester

2.
A multi
-
cystic lesion in the last months of gestation &
neonatal period

3.
Pure
astrogliosis

with no cystic component in the mature
brain

Outcome of brain damage

Low C. et al. Early destructive lesions in the developing brain. Clinical and electrographic correlates
Arq

Neuropsiquiatr

2007; 65 (2
-
B):
416
-
422

Types of brain damage outcome


Encephalomalacia
:
Occurs in the mature brain which reacts to a
brain injury with significant
astrocytic

proliferation resulting in a
lesion that contains soft brain which is
characterized by
astroglial

proliferation and
an irregular wall composed by reactive
astrocytes




Gliosis:
Is primarily an
astrocytic

reaction. Gliosis
is
a nonspecific
reactive change that
occurs
in
response to
brain
injury. Reactive
gliosis
may
be
encountered during
the early organizing phases of
injuries

or demyelinating
conditions
.
Reactive astrocytes tend to
be evenly
distributed within
the
tissue.



They are synonyms!!!

Encephalomalacia

vs

gliosis

Marie Rivera
-
Zengotita
, MD and Anthony T.
Yachnis
,
MD

Gliosis Versus
Glioma
?: Don’t Grade Until You
Know

Adv

Anat

Pathol

Volume 19,
Number 4, July 2012

a
)


axial T2 in a 5
-
month
-
old infant with hydrocephalus, no significant abnormal signal
intensity in the deep WM, b
-
c) MRI 6 years later shows asymmetric abnormal T2 and
FLAIR
hyperintensities

in the deep WM surrounding the shunt catheter (arrow)
representing gliosis.


Gliosis post VP shunt

a

b

c


Porencephaly is a form of diffuse brain destruction in which there is formation of a
smooth
-
walled, fluid
-
filled cavity, with precise limits surrounded by little or no
perilesional gliosis



It results from a very early insult (at the end of 2
nd

trimester or early 3
rd

trimester),
whereby the affected immature brain is still unable to mount a significant astrocyte
reaction

Porencephaly

Low C. et al. Early destructive lesions in the developing brain. Clinical and electrographic correlates
Arq

Neuropsiquiatr

2007; 65 (2
-
B): 416
-
422

26 weeks

Day 1

4 months

Porencephaly

results from an injury
around 20 w of GA

Preterm neonate with
grade IV IVH

Porencephaly

11
-
year
-
old child with right hemiparesis and previous history of prematurity. MRI shows
replacement of the cerebral mantle in the left
frontoparietal

region by CSF with a residual
thin layer of periventricular tissue that prevents its junction with the left lateral ventricle.
Please note the lack of GM in the
smooth wall of the fluid
-
filled cavity
with precise limits
surrounded by little
gliosis.

Porencephaly

6
-
month
-
old infant, born at 26 weeks of GA. MRI shows
porencephaly

in
bilateral frontal lobes. The containing membranes are
leptomeninges

(arrows).
There is a residual thin layer of deep white matter in bilateral frontal lobes.
Please note the lack of GM in the
smooth wall of the fluid
-
filled cavity
with
precise
limits which are the main characteristics of
porencephaly
.

MCE shows irregular walls and gliosis.
Schizencephaly

is surrounded by Grey
matter.

Destruction of the brain mantle (cortex and WM) which has been
replaced by CSF. It could be considered as a
porencephaly

of the
entire cerebrum but posterior fossa structures. The
falx

is intact and
separate
thalami.

The containing membranes are composed by
leptomeninges
.

Hydrancephaly

Low C. et al. Early destructive lesions in the developing brain. Clinical and electrographic correlates
Arq

Neuropsiquiatr

2007; 65 (2
-
B): 416
-
422


MCE is a form of diffuse brain damage characterized by formation of septated
cavitations with imprecise limits & surrounded by moderate to intense glial reaction


It results from an insult that occurs at the end of pregnancy, during delivery or the
first days of life, hence affecting a more mature brain that is able to express a
relatively more significant astrocytic response

Multicystic

Encephalomalacia

(
MCE
)

Low C. et al. Early destructive lesions in the developing brain. Clinical and electrographic correlates
Arq

Neuropsiquiatr

2007; 65 (2
-
B): 416
-
422

a

b

c

d

a
-
b) Axial T2 and DWI in a 3
-
week
-
old infant with meningitis show diffuse multiple cortical and subcortical foci of
abnormal diffusion restriction and T2
hyperintensities
,

c
-
d) 2 weeks later diffusion restriction has resolved but there is
diffuse cortical and subcortical multifocal MCE.

a
-
b: MRI in a 1
-
year
-
old with right upper extremity spasticity shows a MCE involving the left MCA
territory, the event likely occurred in perinatal period; c
-
d: CT in a 3
-
year
-
old post head trauma
showing parenchymal bleeding in the left temporal lobe, a few weeks later the MRI showed MCE
replacing the parenchymal hematoma.


In both cases surrounding walls of the cystic cavities are irregular and show associated gliosis

Examples of MCE

a

b

c

d


An appropriate pathological definition for this term in humans was
not found. In
P
ubmed
, this term is only used in a few references, all
of them in animals.


We suggest to avoid its use in the description of brain lesions.

Leukoencephalomalacia


White matter (WM) disorders

and
leukoencephalopathies

are synonyms.


Defined
as all conditions in
which WM is predominantly
affected
.


Either myelin or a combination of
myelin and
other
WM
components
are
involved.




WM
disorders comprise all
myelin disorders, but
also,
other process as WM infections, infarctions,
etc
,
which may
affect
various
white
matter components
nonselectively
.

Leukoencephalopathy

Van der Knapp M,
Valk

J.
Magnetic
resonance
of
myelination
and
myelin disorders
3
rd

edition. Berlin: Springer; 2005: 16

There are several
definitions:


Seitelberger

(1984
):

degenerative demyelinating processes caused
by metabolic disorders


Morell

and
Wiesmann

(
1984):

disorders
affecting primarily
oligodendroglial

cells or
myelin. The
disorders have
to be of endogenous origin with a
pattern compatible
with
genetic transfer of a
metabolic defect
. The clinical criterion is a steadily
progressive
deterioration
of
function.


Menkes

(1990
):

group
of genetically
transmitted diseases
in which abnormal metabolism
of
myelin
constituents
leads to progressive
demyelination.


Common concepts:
demyelination,
inborn errors of
metabolism and heritability.


Leukodystrophies

=

inherited demyelinating disorders.

Leukodystrophies

Van der Knapp M,
Valk

J. Magnetic resonance of myelination and myelin disorders 3
rd

edition. Berlin: Springer; 2005: 16


Demyelination:

process of myelin
loss caused by primary and selective
abnormality of
either oligodendroglia or of
the
myelin
membrane
itself.


Demyelinating disorders:

conditions characterized by
demyelination such as
metachromatic
leukodystrophy

and multiple
sclerosis.


Hypomyelination
:

conditions with
a
significant permanent deficit in myelin
deposit.
Its
most extreme variant
is
amyelination
. Ex.
Pelizaeus
-
Merzbacher

disease.


Dysmyelination
:
conditions
in
which the
process of myelination is disturbed,
leading
to abnormal
, patchy, irregular
myelination, but
not necessarily combined
with
myelin loss
.
Ex. amino
acidopathies
,
damaged structure
of
unmyelinated

WM after
perinatal
hypoxia or encephalitis.


Retarded myelination:

disorders in
which the deposition of myelin is
delayed, but
progressing.
Ex:
inborn errors of
metabolism with
early onset, malnutrition,
hydrocephalus.

Definitions and types of
myelination disorders

Van der Knapp M,
Valk

J. Magnetic resonance of myelination and myelin disorders 3
rd

edition.
Berlin: Springer; 2005: 16


Leukomalacia
:
Destruction
of the
deep WM
of the
brain.
It tends to
occur mainly in premature or
newborns
who have been deprived
of oxygen or have poor blood flow to parts of the brain.
Intrauterine infections and premature membrane rupture tend to
predispose infants to this condition
.



Periventricular
Leukomalacia

(PVL
) :
Is the destruction of deep WM
but also of grey matter (thalami

and basal ganglia) in preterm
infants as a result of hypoxic
-
ischemic injury, infections, metabolic
diseases , etc
. It is also known as
WM injury of
prematurity,
but
given the involvement of grey matter, the best term is

encephalopathy of prematurity.

Leukomalacia

and PVL

Encephalopathy of prematurity AKA PVL or
leukomalacia

8
-
year
-
old with spastic
quadriparesis

and past
medical history of
prematury
. MRI shows
anterior and posterior deep WM volume loss
and gliosis . On sagittal view, the corpus
callosum is markedly thinned representing WM
damage


Encephalopathy
is
not a
diagnosis but a descriptive term for a
syndrome of
global brain
dysfunction
.



Morbidity
and mortality in these
children remains
high but
prompt recognition of
the
encephalopathic

state and
appropriate and
timely investigations
will help identify treatable
causes and
can minimise further neurological impairment
.



Causes: Infections, ADEM, trauma, non accidental trauma,
autoimmune disorders, epilepsy, toxins,
leukoencephalopathies
,
etc.

Encephalopathy

Davis E, Connolly D,
Mordekar

S Arch
Dis Child
2012;97:452

458.

a
-
c) meningeal enhancement &

t2/flair
hyperintensity

in the right frontal cortical
region in a 3
-
year
-
old


child diagnosed of
meningitis, d
-
e) 1 year follow
-
up MRI shows
gray and white matter volume loss but
gliosis.

Is the volume loss result of poor
astrocytic

reaction or increased
destruction of regenerative cells?


Brain
v
olume loss post meningitis

a

b

c

d

e

Brain
v
olume loss, what is its significance?

a) 4
-
day
-
old with
intraparenchymal

hematomas (thin arrows) in
the right thalamus
,
right
caudothalamic

groove and right occipital horn periventricular WM, b)
2 years later
the
hematomas have been
replaced with fluid and the
right thalamus, right
caudothalamic

groove
and deep
right occipital periventricular WM show
volume
loss
but not significant
gliosisi

Again, Is the volume loss result of poor
astrocytic

reaction or
increased destruction of regenerative cells?

a

b


Reactive gliosis is the main characteristic of gliosis /
encephalomalacia


Leukoencephalopathy

is the destruction of WM including
myelinating

disorders


The use of the term
l
eukoencephalomalacia

should be avoided


Porencephaly
, MCE and gliosis are result of a continuous between limited


complete
astrocytic

reaction and limited


complete reabsorption
of necrotic brain tissue

Conclusion: Are
porencephaly
,
MCE,
leukoencephalomalacia

and gliosis synonyms
? NO

Porencephaly

MCE

gliosis

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