Transcript Neural plasticity and recovery of function

Neural plasticity and
recovery of function
Lect. Thawatchai Lukseng, M.Sc (Physiology)
School of Allied Health Sciences and Public Health
Contents:
• Introduction
– Upper and lower motor neuron lesion
– Pathophysiology of ischemic injury
• Neuronal plasticity
• Recovery of function
– Recovery patterns for specific neurological
impairments
– Prediction of functional recovery
7/20/2015
2
7/20/2015
3
Upper motor neuron and lower motor neuron
lesion (UMNL & LMNL)
• Corticobulbospinal tract
– Corticobulbar tract
– Corticospinal tract
• Anterior corticospinal tract (10-20%)  Uncross
• Lateral corticospinal tract (80-90%)  Crossed at
medulla oblongata
7/20/2015
4
7/20/2015
5
Upper motor neuron
7/20/2015
6
7/20/2015
7
7/20/2015
8
Introduction
CNS injury
CNS changes
Functional recovery
Impair cerebral blood flow
• Control of CSF
• Control of cerebral metabolism
7/20/2015
9
Introduction
• Pathophysiology of ischemic injury
– Autoregulation of BF
– Increased oxygen extraction
• Failure of aerobic metabolism (mild)
• Disturbed Ca2+ homeostasis (moderate)
• Ca2+ overload (severe)
7/20/2015
10
Neural plasticity
• Neural (adj.) = involving a nerve or the system of nerves
that includes the brain
• Plastic (adj.) = soft enough to be changed into a new shape
• Neuroplasticity, brain plasticity or brain malleability
• The brain's ability to reorganize itself by forming new neural
connections
• Neurons (nerve cells) in the brain to compensate for injury
and disease and to adjust their activities in response to new
situations or to changes in their environment
7/20/2015
11
Memory
• Memory refers to the storage and retrieval
of information.
• No absolute boundaries between learning
and memory.
• Learning and memory may be viewed as a
being on a time continuum.
7/20/2015
12
Divisions of Long-term Memory
7/20/2015
13
Locating the Engram
• Karl Lashley observed the • Lashley believed that the
engram was distributed
effects of lesions on rats’
across the cortex.
maze learning.
• The larger the amount of
cortex damaged, the more
errors the rats made.
7/20/2015
14
The Delayed Nonmatching to
Sample Task
• Monkeys with
medial temporal
lobe damage do
poorly on the
DNMS task.
• The DNMS task
requires the ability
to form long-term
memories.
7/20/2015
15
Long-Term Synaptic Enhancement
• Long-Term Potentiation (LTP) ~ Rapid and
sustained increase in synaptic efficacy
following a brief but potent stimulus
• Best studied in the hippocampus
• Induction of LTP occurs at the
postsynaptic site and requires the
conjunction of pre and post-synaptic
activity
• On the order of hours, days or longer
7/20/2015
16
7/20/2015
17
The Anatomy of the Hippocampus
in Humans
7/20/2015
18
Producing Long-Term Potentiation
in the Rat
7/20/2015
19
Long-Term Potentiation
7/20/2015
20
LTP and the NMDA Receptor
7/20/2015
21
7/20/2015
22
7/20/2015
23
7/20/2015
24
LTP Shares Characteristics with
Long-term Memory
• Both LTP and long-term memories last
indefinitely.
• Both LTP and long-term memories result
from very brief input.
7/20/2015
25
The Hippocampus and Human
Memory
• The right hippocampus is active during
spatial memory processing and the left
hippocampus is active during verbal
memory processing.
• Rostral portions of the hippocampus are
more active during encoding, and caudal
portions are active during retrieval.
7/20/2015
26
Brain injury
• Neuron and axon injuries
• Degeneration of other neuron
– Both above and beneath
• CNS dysfunction
7/20/2015
27
Brain recovery
• 2 stages
• Early (Spontaneous) recovery
• 2-3 first days (or 3-4 first weeks)
• Reduction of brain edema
• Increasing of BF from nearly surroundings
• Neural plasticity
•
•
•
•
7/20/2015
Depending on use and experience
Occur continuously throughout recovery (fast/slow)
Short-term functional plasticity (synaptic connection ability)
Structural plasticity (neural modifiability)
28
Brain recovery mechanisms
• There are many theories that explain this
events
– von Monakow’s diaschisis theory (1895-1913)
• Diaschisis (from edema)
– (Diaschisis (from Greek), meaning "shocked throughout")
• Resolution of diaschisis
– Recovery of synaptic effectiveness
• Only emphasize in injured neuron
• Depression of axon (from edema)
• recovery
7/20/2015
29
Brain recovery mechanisms (cont.)
– Denervation supersensitivity
• Hypersensitivity of neurotransmitter (NT) of
postsynaptic membrane
– Recruitment of silent synapses
– Neural sprouting
• Regenerative synaptogenesis
– Old axon (injured) into new axon
• Reactive synaptogenesis (collateral sprouting)
– Neighboring normal axon  Old axon (injured)
7/20/2015
30
Regeneration following in Central Nervous
System: Collateral Sprouting
7/20/2015
31
Neuronal Degeneration in Necrosis
Anterograde & Retrograde
Wallerian degeneration
7/20/2015
32
Regeneration in the Peripheral Nervous System
(e.g., spinal cord injuries)
7/20/2015
33
Advantage of neural sprouting mechanisms
• Increasing of effectiveness of synapse
• Motor relearning
• Compensation
axonal regrowth
• occurs in periphery in mammals
• no regrowth in mammalian CNS
7/20/2015
34
CNS
PNS
7/20/2015
35
Brain recovery mechanisms (cont.)
– Redundancy theory
• Various area  same function
• Believe that violent status depending on normal neurons (not
injured) > lesion area
– Vicarious function
• Latent motor functions of neurons
– Functional reorganization
• Reorganization to control other movement
– Behavioral strategy change
• Subsituation
• E.g. sensory neuron induce movement
• Other movement supplemented the movement dysfunction
7/20/2015
36
Cellular response to learning and memory
• How does learning change the structure and
function of neuron in the brain?
– CNS structural changes occur because of the
interaction between both genetic and experiential
factors
– There appears to be use-dependent competitions
among neurons for synaptic connections (transient
and long term modification of synapses)
– Memory
• Required synthesis of new proteins and the growth of new
synaptic connections
7/20/2015
37
Recovery of function
• Recovery patterns for specific neurological
impairments
– Recovery of function is fastest during the early
weeks and up to 3 months after stroke
– Statistically significant recovery occurring for up
to 6 months
– Some patients continue to recover function
between 6 months-1 year but not have
statistical significance
7/20/2015
38
Recovery of function (cont.)
• Motor recovery
– Tend to plateau more quickly than functional
recovery
– Small motor changes seen after 8-12 weeks
– Recovery of arm movement is usually less
complete than leg movement
– Full arm recovery, if it occurs, is usually
complete by 8 weeks
– At 3 months, 5% of all stroke have significant
shoulder pain and 8% have decreased ROM
7/20/2015
39
Motor homunculus
7/20/2015
40
Prediction of functional recovery
• Prognostic indicators
– Level of consciousness (GCS)
– Hematoma (lesion) size
– Age (over 69-poor prognosis), young>old
• Sex or side of stroke no relation
• Final level of recovery measured 1-3 wks
post onset  best predictors
• Waiting at least 7 days  exclude
transient deficits patients
7/20/2015
41
Important factors to brain recovery
• Age
– depending on lesion
•
•
•
•
Quality of the lesion
Experience before ill
Training
Environment
7/20/2015
42
Summary
• Introduction
– Upper and lower motor neuron lesion
– Pathophysiology of ischemic injury
• Neuronal plasticity
• Recovery of function
– Recovery patterns for specific neurological
impairments
– Prediction of functional recovery
7/20/2015
43
7/20/2015
44