Presentation on Neuroplasticity, Physiology

1. Neuroplasticity and
Brain Repair After Stroke
Reagon Heikes
Physiology 247

2. This is your brain: it’s pretty rad.
 Composed of association neurons and accompanying neuroglia.
 Neurons:
-receive sensory information
-direct motor neurons
-perform higher brain functions such as learning and memory
 Grey matter:
-contains neuron cell bodies and dendrites
-in cortex (surface layer) of brain and nuclei (deeper portion)
 White matter:
-contains axon tracts, under cortex and surrounding
nuclei
 Adult brains have 100 billion neurons
 Your brain receives 15% of your total body blood flow per minute

3. Cerebrovascular Incident
(Stroke)
 Leading cause of adult chronic disability in the U.S. and 3rd
leading cause of death in U.S.
 A stroke is: an interruption of blood supply to the brain
-oxygen deprived neurons with out their normal metabolic substrates
cease to function in seconds.
 Show structural damage in 2 min.
 Ischemic: most, caused by blockage (blood clot)
 Hemorrhagic: less common, bleeding in brain.
 Only treatment is to administer clot busting medications with
in hours of the stroke.

4. Necrotic and Apoptotic cell death
 When neurons are unable to maintain their normal ionic gradients there is an ion
and water imbalance that leads to Apoptotic and Necrotic cell death.
 Apoptosis- programmed cell death, normal physiological process
 Necrosis: cell death under unfavorable physiological or chemical circumstances
(hypoxia or trauma) cell swells and lysis.

5. Recovery:
 The dead neurons ultimately impair sensory and motor function
 Many patients survive the stroke and undergo some
spontaneous recovery aided by rehabilitative therapy
Distinctions:
 Functional Recovery:
-enhanced sensory and motor performance that can
continue for several years
-can be facilitated by behavioral therapy
-clinically referred to as recovery even though most post-stroke
behavior is not identical to pre-stroke behavior

6. Recovery:
 Because of the highly specific functions of lost neurons it is hard
to determine the difference between true brain recovery and
behavioral compensation or a combination
 True (pure) Brain Recovery:
-occurs in small areas of the cortex where the crucial tissue was
spared.
-motor and sensory cortices are loosely organized into a map of
functional body parts and have high use-dependent plasticity

7. Recovery:
 Motor maps reflect coupling of
specific motor cortex neurons to
muscles like sensory cortex
neurons. They enable learning
and expression of movements.
 This essentially is creating a
“memory trace” that the stroke
destroys. True recovery would be
to replace those circuits.

8. Stroke Damage: Stanford

9. Still your brain: I told you it was cool.
 Mechanisms used in stroke recovery are similar to those used in plasticity in
a healthy brain.
 There is a large amount of diffuse and redundant connectivity in the Central
Nervous System.
 Conventional thought:
-definitive synaptic connectivity formed in development and shaped
by behavior
 Science says: brain functions are spatially distributed
-Neurons that contribute to complex functions such as a memory
trace are not localized to a single region. Instead they are
distributed throughout the cortex.
-Signals are routed along multiple pathways. The connectivity is
redundant– there’s options.

10. Reduced Lateralization
 Conventional thought:
-our body parts are controlled by neurons in the opposite
cerebral hemisphere
 Science says: Ipsilateral pathways
-pathways present in the brain and spinal cord on the same
side of the body to which they connect
 This reduced lateralized activation by use of neural networks in
opposite side from infarction.
 Also, use pathways around the infarction.
 Indicates severity of injury and amount of achieved recovery.
 Research on patients with smaller strokes shows restoration of
bilateralization better than larger strokes.

11. Cortical Remapping
 There is intense competition for
available remapping territory.
 Penumbra: area of tissue
surrounding the dead tissue with
reduced blood flow. Shows on
MRI.
 This region tries to recover.
Compromised circuits look for a
way to reroute though adjacent
healthy tissue.
 Depending on size of stroke may
have to travel further for healthy
tissue with same function- ex:
contralaterally, from motor cortex
to premotor cortex.

12. Early Enrichment
 Important neurological genes
and proteins are expressed in
high levels for neurological
growth in early brain
development and then declines
with age.
 Ex: Brain-derived neurotropic factor
BNDF, extracellular matrix factor
NOGO, ephrin A5
 2nd limited period following a
stroke.
 Means critical period after stroke
for rehab.
 Rat study 2004: 5, 14, 30
days after “stroke”
 5 and 14 days significantly
better recovery than 30
days.

13. Early Enrichment
 Debate over best timing of rehabilitation after stroke.
 Evidence shows that longer gaps mean worse
outcomes and longer hospital stays.
 The recovery window never completely closes like with
any learning. Yet, far more plasticity early on.

14. Stem Cells
 Stem cell: undifferentiated precursor cell, can become virtually any
cell in the body. Embryonic cells are considered the ‘gold standard’.
 In theory: should be able to inject at site of tissue damage and it
would regenerate.
 In reality: Safety concerns: stem cells grow out of control, can form
tumors, rejection of immune response from patients.
 Preclinical studies: human and rodent stem cells transplanted in to
rats. Migrated to lesion and developed into electrophysiologically
and anatomically mature neurons.
 2013: 1st ever trials to test safety of stem cell treatment for stroke on
humans. UK. Injected with ReN001, originally 12 week old fetus cells.
 No harmful side effects. Modest improvement in every day function
and cognitive abilities in 5/6 patients.

15. Questions?

16. References
 Cohen, Leonardo G, Dimyan, Michael A. (2011) Neuroplasticity in the context
of motor rehabilitation after stroke. Nature Reviews Neurology. [Online Report]
Academic One File.
http://go.galegroup.com/ps/i.do?id=GALE%7CA249137142&v=2.1&u=ksstate_
ukans&it=r&p=AONE&sw=w&asid=5e50f311c960652fa9bfa38add9543c1.
[2014]
 Fox, Stuart I. Human Physiology: Thirteenth Edition. McGraw Hill. 2014,p. 12, p.
209-240.
 Murphy, Timothy H, Corbett, Dale. (2009) Plasticity during stroke recovery: from
synapse to behavior. [Online Journal]. Nature Reviews Neuroscience.
http://www.nature.com.www2.lib.ku.edu:2048/nrn/journal/v10/n12/pdf/nrn273
5.pdf [2014].
 Paddock, Catharine. Stroke Patients Show Signs of Recovery Following Stem
Cell Trial. Medical News Today. 2013 [Online].
http://www.medicalnewstoday.com/articles/261084.php. [7/2/2014].
 Wierenga, E.A, Van Noorden, C.J.F, Van Der Heijden, F.L. Cell Cycle. [Online]
Amsterdam: University of Amsterdam Academic Medical Center, 2010, p.54.
http://os1.amc.nl/celbiologie/20102011/auc/celcyclus/php/a.php. [2014].