Reorganization of Eko Arisetijono

Neural Network After Div Neurovaskular

Stroke Departemen Neurologi

FKUB/RS Saiful Anwar Malang
Preface
 As 2010 more than 33 million stroke survivors worldwide (Veign
et all)

 At 2030 more than 70 million stroke survivors worldwide

(Krisnamurthi et all)

 Disability heavily between 20-75 years of age(Hankey et all)

 Hemiparesis of upper extremities dominate Interfering with life

quality and productivity
Challenges
 Despite thousands of promising preclinical studies of
neuroprotective treatments that minimize tissue damage
from stroke, their effective translation to clinical stroke
populations has been disappointing

 Only few patient receiving thrombolityc treatment due to

short window therapay and risk of bleeding

 Need to better understand and better treat the functional

aftermath of this damage continues.
Functional Improvent after
Stroke
 Some degree spontaneus
improvement after stroke

 Depend on degree of brain cell

damage

 Depend on Brain Neurovascular Unit

  Resolution of penumbra region
Mechanism of
improvement  Surviving neurons reorganize their
connectivity patterns
 Brain Plasticity

The nervous system accomplishes its

function not by increasing diversity of
its component parts but by replicating
a small number of simple structures
and modifying the specificity with
those elements are interconnected
with one another
Neuroplastisitas
Major mechanisms involved
in brain plasticity :
- Inhibition of apoptosis
- Angiogenesis
- Neurogenesis
- Gliagenesis
- Neurotransmitter’s
modulation
- Synaptogenesis

Brain Sci. 2013; 3: 1395-1414

Regenerative Response to
Stroke
 Initiates a complex cascade of cellular,molecular and
metabolic events

Cerebral ischemia Infarct progress  neurovascular lesion worsen

Targetting of multiple factors and cell including

Reorganization since ischemia glia,vascular and inflammatory cells
BBB disruption  edema formation,secondary brain
injury
Elisabetta Bandera. Stroke. Cerebral Blood Flow Threshold of
Ischemic Penumbra and Infarct Core in Acute Ischemic Stroke,
Volume: 37, Issue: 5, Pages: 1334-1339, DOI:
(10.1161/01.STR.0000217418.29609.22)
 Ischemic stroke intervention requires protection of the ischemic penumbra.

Penumbra Identifying Penumbra region into irreversible and reversible area is very important

Neuroimaging of the penumbra is a strategy for detecting tissue at risk especially when
up to 44% of patients may still retain penumbral tissue 18 h after stroke

Spesific treatment for reversible area of penumbra

Reversible and proper treatment - will lead to neurogenesis and angiogenesis into
focal penumbra area

Neurogenesis and angiogenesis --> long term brain recovery after stroke

This Photo by Unknown Author is licensed under CC BY-SA-NC This Photo by Unknown Author is licensed under CC BY-NC-ND
Neuroimaging
MRI DWI/PWI
Penumbra to Neurogenesis on animal model

Proper treatment for penumbra

Increase neurogenesis

Promotes continues proliferation into the peri-infarct areas

Ischemia
Neuroblast
Induce
migration to the
Neurogenesis
damage area

Induce Repair brain

angiogenesis structural

Induce
Induce
fungsional
mediator
restoration
 Ischemic  triggers molecular and Cellular repair
mechanism

BDNF expression

Neural outgrowth

Synaptogenesis

Neuronal proliferation

Neural progenitor proliferation

Cell migration
 Neurogenesis
Neurogenesis is the process by which
new neurons are formed in the brain

Ischemic injury induces neurogenesis and

promotes migration of neuroblasts along
the blood vessels into damaged area

Repair implement structural and

functional restoration of injured brain
 Axonal remodeling

Blocking of axonal Administration of

outgrowth inhibitors
(e.g., anti-NogoA immunotherapy,
Wahl et al., 2014; chondroitinase
ABC, Soleman et al., 2012)
axonal outgrowth-
promoting factors (e.g.,
neurotrophin, Duricki et al., 2016;
basic fibroblast growth factor,
Ramirez et al., 1999)
Cell transplantation
(neural stem cells, Daadi et al.,
2010; mesenchymal stem cells,
Liu et al., 2008)

Brain stimulation Rehabilitation

(e.g., optogenetic stimulation,
Cheng et al., 2014) therapy.
Synaptogenesis

 Synapses, synaptic vesicles,

axon terminals, and spines
were reported to degenerate
with a reduction in their
numbers and sizes, until after
4 days
 Recover 1-12 weeks after
ischemic insult
 Promotes synaptic plasticity
 Modulate synaptic protein
expresions
 Neurogenesis - functional recovery
Newly generated neural Excisting Brain
cells Circuit

Proliferation

Migration

Differentiation

Integration
Motor System Reorganization after
Theresa A. Jones
Stroke
Conclusion and Future
Perspective
Stimulate by
widespread
reorganization of
Reorganization of
connectivity of surviving
motor and sensory
neuron,neurogenesis,d
cortical maps of both
endritic
hemisphere
remodelling,synpases
formation of both
hemisphere

Bilateral changes of
Behavioural neural activity and
manipulation functional
connectivity patterns

Neuronal activity
modulation
Terima
kasih