Download Causes of Brain Damage

PowerPoint Presentation for
Biopsychology, 8th Edition
by John P.J. Pinel
Prepared by Jeffrey W. Grimm
Western Washington University
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Chapter 10
Brain Damage and
Neuroplasticity
Can the Brain Recover from
Damage?
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Causes of Brain Damage
Brain tumors
 Cerebrovascular disorders
 Closed-head injuries
 Infections of the brain
 Neurotoxins
 Genetic factors

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Brain Tumors


A tumor (neoplasm) is a mass of cells
that grows independently of the rest of
the body – a cancer
20% of brain tumors are meningiomas –
encased in meninges


Encapsulated, growing within their own
membranes
Usually benign, surgically removable
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Brain Tumors Continued

Most brain tumors are infiltrating



Grow diffusely through surrounding tissue
Malignant, difficult to remove or destroy
About 10% of brain tumors are metastatic
– they originate elsewhere, usually the
lungs
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FIGURE 10.3 An MRI of Professor
P.’s acoustic neuroma. The arrow
indicates the tumor.
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Cerebrovascular Disorders

Stroke – a sudden-onset cerebrovascular
event that causes brain damage



Cerebral hemorrhage – bleeding in the brain
Cerebral ischemia – disruption of blood supply
Third leading cause of death in the U.S.
and most common cause of adult disability
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Cerebrovascular Disorders
Continued


Cerebral Hemorrhage – blood vessel ruptures
 Aneurysm – a weakened point in a blood vessel
that makes a stroke more likely; may be
congenital (present at birth) or due to poison or
infection
Cerebral Ischemia – disruption of blood supply
 Thrombosis – a plug forms in the brain
 Embolism – a plug forms elsewhere and moves
to the brain
 Arteriosclerosis – wall of blood vessels thicken,
usually due to fat deposits
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Damage Due to Cerebral
Ischemia




Does not develop immediately
Most damage is a consequence of excess
neurotransmitter release – especially
glutamate
Blood-deprived neurons become
overactive and release glutamate
Glutamate overactivates its receptors,
especially NMDA receptors leading to an
influx of Na+ and Ca2+
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Damage Due to Cerebral
Ischemia

lnflux of Na+ and Ca2+ triggers



the release of still more glutamate
a sequence of internal reactions that ultimately
kill the neuron
Ischemia-induced brain damage



takes time
does not occur equally in all parts of the brain
mechanisms of damage vary with the brain
structure affected
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FIGURE 10.5 The cascade of
events by which the strokeinduced release of glutamate
kills neurons.
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Closed-Head Injuries



Brain injuries due to blows that do not
penetrate the skull – the brain collides with the
skull
 Contrecoup injuries – contusions are often
on the side of the brain opposite to the blow
Contusions – closed-head injuries that involve
damage to the cerebral circulatory system;
hematoma (bruise) forms
Concussions – when there is disturbance of
consciousness following a blow to the head
and no evidence of structural damage
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Closed-Head Injuries
Continued

While there is no apparent brain damage
with a single concussion, multiple
concussions may result in a dementia
referred to as “punch-drunk syndrome”
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FIGURE 10.6 A CT scan of a
subdural hematoma. Notice
that the subdural hematoma
has displaced the left lateral
ventricle.
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Infections of the Brain

Encephalitis – the resulting inflammation
of the brain by an invasion of
microorganisms

Bacterial infections




Often lead to abscesses, pockets of pus
May inflame meninges, creating meningitis
Treat with penicillin and other antibiotics
Viral infections


Some preferentially attack neural tissues
Some can lie dormant for years
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Neurotoxins



May enter general circulation from the GI
tract or lungs, or through the skin
Toxic psychosis – chronic insanity
produced by a neurotoxin
The Mad Hatter – hat makers often had
toxic psychosis due to mercury exposure
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Neurotoxins Continued


Some antipsychotic drugs produce a
motor disorder called tardive dyskinesia
Some neurotoxins are endogenous
(produced by the body)

e.g. Auto-immune disorders
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Genetic Factors


Most neuropsychological diseases of genetic
origin are associated with recessive genes-why?
Down syndrome



0.15% of births, probability increases with
advancing maternal age
Extra chromosome 21 created during ovulation
Characteristic disfigurement, mental retardation,
other health problems
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Programmed Cell Death

All six causes of brain damage produce
damage, in part, by activating apoptosis
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Neuropsychological Diseases



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
Epilepsy
Parkinson’s disease
Huntington’s disease
Multiple sclerosis
Alzheimer’s disease
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Epilepsy
Primary symptom is seizures, but not
all who have seizures have epilepsy
 Epileptics have seizures generated
by their own brain dysfunction
 Affects about 1% of the population
 Difficult to diagnose due to the
diversity and complexity of epileptic
seizures

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Epilepsy Continued



Types of seizures
 Convulsions – motor seizures
 Some are merely subtle changes of thought,
mood, or behavior
Causes
 Brain damage
 Genes – over 70 known so far
 Faults at inhibitory synapses
Diagnosis
 EEG – electroencephalogram
 Seizures associated with high amplitude
`
spikes
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Epilepsy Continued

Seizures often preceded by an aura, such as
a smell, hallucination, or feeling



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Aura’s nature suggests the epileptic focus
Warns epileptic of an impending seizure
Partial epilepsy – does not involve the whole
brain
Generalized epilepsy – involves the entire
brain
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Partial Seizures

Simple



Symptoms are primarily sensory or motor or
both (Jacksonian seizures)
Symptoms spread as epileptic discharge
spreads
Complex



often restricted to the temporal lobes
(temporal lobe epilepsy)
Patient engages in compulsive and repetitive
simple behaviors (automatisms)
More complex behaviors seem normal
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FIGURE 10.8 Cortical electroencephalogram
(EEG) record from various locations on the
scalp during the beginning of a complex
partial seizure.
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Generalized Seizures

Grand mal


Loss of consciousness and equilibrium
Tonic-clonic convulsions

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Rigidity (tonus)
Tremors (clonus)
Resulting hypoxia may cause brain damage
Petit mal


Not associated with convulsions
A disruption of consciousness associated
with a cessation of ongoing behavior
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Parkinson’s Disease


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A movement disorder of middle and old
age affecting about .5% of the population
Tremor at rest is the most common
symptom of the full-blown disorder
Dementia is not typically seen
No single cause
Associated with degeneration of the
substantia nigra; these neurons release
dopamine to the striatum of the basal
ganglia
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Parkinson’s Disease
Continued



Almost no dopamine in the substantia nigra
of Parkinson’s patients
Autopsies often reveal Lewy bodies
(protein clumps) in the substantia nigra
Treated temporarily with L-dopa
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Parkinson’s Disease
Continued


Linked to about ten different gene
mutations
Deep brain stimulation of subthalamic
nucleus reduces symptoms, but
effectiveness slowly declines over months
or years
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Huntington’s Disease

A rare, progressive motor disorder of middle
and old age with a strong genetic basis

Huntingtin gene





single, dominant gene
Begins with fidgetiness and progresses to
jerky movements of entire limbs and severe
dementia
Death usually occurs within 15 years
Caused by a single dominant gene
First symptoms usually not seen until age 40
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Multiple Sclerosis




A progressive disease that attacks CNS
myelin, leaving areas of hard scar tissue
(sclerosis)
Nature and severity of deficits vary with
the nature, size, and position of sclerotic
lesions
Periods of remission are common
Symptoms include visual disturbances,
muscle weakness, numbness, tremor, and
loss of motor coordination (ataxia)
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Multiple Sclerosis Continued



Epidemiological studies find that incidence
of MS is increased in those who spend
childhood in a cool climate
MS is rare amongst Africans and Asians
Only some genetic predisposition and
only one chromosomal locus linked to MS
with any certainty
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Multiple Sclerosis Continued

Recent focus on epigenetic mechanisms



Gene/environment interactions
An autoimmune disorder – immune
system attacks myelin
Drugs may retard progression or block
some symptoms
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FIGURE 10.11 Areas of sclerosis (see arrows)
in the white matter of a patient with MS.
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Alzheimer’s Disease



Most common cause of dementia –
likelihood of developing it increases with
age
Progressive, with early stages characterized by confusion and a selective decline
in memory
Definitive diagnosis only at autopsy –
must observe neurofibrillary tangles and
amyloid plaques
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Alzheimer’s Disease
Continued




Several genes associated with early-onset AD
synthesize amyloid or tau, a protein found in the
tangles
Which comes first, amyloid plaques or neurofibrillary tangles? Genetic research on early-onset
AD supports amyloid hypothesis (amyloid first)
Decline in acetylcholine levels is one of the earliest
signs of AD
Effective treatments not yet available

Immunotherapy is promising in animal models
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FIGURE 10.13 The typical distribution of
neurofibrillary tangles and amyloid plaques
in the brains of patients with advanced
Alzheimer’s disease. (Based on Goedert,
1993, and Selkoe, 1991.)
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Animal Models of Human
Neuropsychological Diseases



Experiments regarding neuropathology are not
usually possible with human subjects
Animal models are often utilized, for example:
Kindling model of epilepsy


Transgenic mouse model of Alzheimer’s


Experimentally induced seizure activity
Mice producing human amyloid
MPTP model of Parkinson’s

Drug-induced damage comparable to that seen in PD
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Kindling Model of Epilepsy

A series of periodic brain stimulations
eventually elicits convulsions – the
kindling phenomenon


Neural changes are permanent
Produced by stimulation distributed over time
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Kindling Model of Epilepsy
Continued


Convulsions are similar to those seen in
some forms of human epilepsy – but they
only occur spontaneously if kindled for a very
long time
Kindling phenomenon is comparable to the
development of epilepsy (epileptogenesis)
seen following a head injury
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Transgenic Mouse Model of
Alzheimer’s Disease



Only humans and a few related primates
develop amyloid plaques
Transgenic – genes of another species have
been introduced
Genes accelerating human amyloid
synthesis introduced into mice


Plaque distribution comparable to that in AD
Unlike humans, no neurofibrillary tangles
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MPTP Model of Parkinson’s
Disease

The Case of the Frozen Addicts




Synthetic heroin produced the symptoms of
Parkinson’s
Contained MPTP
MPTP causes cell loss in the substantia
nigra, like that seen in PD
Animal studies led to the finding that
deprenyl can retard the progression of PD
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Neuroplastic Responses to
Nervous System Damage




Degeneration – deterioration
Regeneration – regrowth of damaged
neurons
Reorganization
Recovery
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Degeneration


Cutting axons (axotomy) is a common way to
study responses to neuronal damage
Anterograde: degeneration of the distal
segment – between the cut and synaptic
terminals


Cut off from cell’s metabolic center – swells and
breaks off within a few days
Retrograde: degeneration of the proximal
segment – between the cut and cell body

Progresses slowly – if regenerating axon makes a
new synaptic contact, the neuron may survive
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FIGURE 10.15 Neuronal
and transneuronal
degeneration following
axotomy.
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Neural Regeneration


Does not proceed successfully in
mammals and other higher vertebrates –
capacity for accurate axonal growth is lost
in maturity
Regeneration is virtually nonexistent in the
CNS of adult mammals and unlikely, but
possible, in the PNS
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Neural Regeneration in the
PNS



If the original Schwann cell myelin sheath
is intact, regenerating axons may grow
through them to their original targets
If the nerve is severed and the ends are
separated, they may grow into incorrect
sheaths
If ends are widely separated, no
meaningful regeneration will occur
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FIGURE 10.16 Three patterns of
axonal regeneration in
mammalian peripheral nerves.
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Mammal PNS Neurons
Regenerate, CNS Don’t


CNS neurons can regenerate if
transplanted into the PNS, while PNS
neurons won’t regenerate in the CNS
Schwann cells promote regeneration



Neurotrophic factors stimulate growth
CAMs provide a pathway
Oligodendroglia actively inhibit
regeneration
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Neural Reorganization

Reorganization of primary sensory and motor
systems has been observed in laboratory
animals following




Damage to peripheral nerves
Damage to primary cortical areas
Lesion one retina and remove the other – V1
neurons that originally responded to lesioned
area now responded to an adjacent area –
remapping occurred within minutes
Studies show large scale of reorganization
possible
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Cortical Reorganization
Following Damage in Humans

Brain-imaging studies indicate there is
continuous competition for cortical space
by functional circuits

e.g. Auditory and somatosensory input may be
processed in formerly visual areas in blinded
individuals
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Mechanisms of Neural
Reorganization

Strengthened existing connections due to
a release from inhibition?


Consistent with speed and localized nature of
reorganization
Establishment of new connections?

Magnitude can be too great to be explained by
changes in existing connections
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Recovery of Function after
Brain Damage




Difficult to conduct controlled experiments on
populations of brain-damaged patients
Can’t distinguish between true recovery and
compensatory changes
Cognitive reserve – education and intelligence
– thought to play an important role in recovery
of function – may permit cognitive tasks to be
accomplished in new ways
Adult neurogenesis may play a role in recovery
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FIGURE 10.21 Increased
neurogenesis in the dentate
gyrus following damage (These
images are courtesy of Carl
Ernst and Brian Christie,
Department of Psychology,
University of British Columbia.)
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Neuroplasticity and the
Treatment of Nervous System
Damage




Reducing brain damage by blocking
neurodegeneration
Promoting recovery by promoting
regeneration
Promoting recovery by transplantation
Promoting recovery by rehabilitative
training
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Reducing Brain Damage by
Blocking Neurodegeneration

Various neurochemicals can block or limit
neurodegeneration




Apoptosis inhibitor protein – introduced in rats via
a virus
Nerve growth factor – blocks degeneration of
damaged neurons
Estrogens – limit or delay neuron death
Neuroprotective molecules tend to also
promote regeneration
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Promoting CNS Recovery by
Promoting Regeneration

While regeneration does not normally
occur in the CNS, experimentally it can be
induced directing growth of axons by


Schwann cells
Olfactory ensheathing cells
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Promoting Recovery by
Neurotransplantation

Transplanting fetal tissue




Fetal substantia nigra cells used to treat
MPTP-treated monkeys (PD model)
Treatment was successful
Limited success with humans
Transplanting stem cells


e.g. Embryonic stems cells implanted into
damaged rat spinal cord
Rats with spinal damage with improved
mobility
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Promoting Recovery by
Rehabilitative Training



Monkeys recovered hand function from
induced strokes following rehab training
Constraint-induced therapy in stroke
patients – tie down functioning limb while
training the impaired one – creates a
competitive situation to foster recovery
Facilitated walking as an approach to
treating spinal injury
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Promoting Recovery by
Rehabilitative Training
Continued

Benefits of cognitive and physical exercise



Correlations in human studies between
physical/cognitive activity and resistance or
recovery from neurological injury and disease
Rodents raised in enriched environments are
resistant to induced neurological conditions
(epilepsy, models of Alzheimer’s, Huntington’s,
etc.)
Physical activity promotes adult neurogenesis in
rodent hippocampus
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Phantom Limbs: Neuroplastic
Phenomena



Ramachandran’s hypothesis: phantom limb
caused by reorganization of the somato-sensory
cortex following amputation
Amputee feels a touch on his face and also on
his phantom limb (due to their proximity on
somatosensory cortex)
Amputee with chronic phantom limb pain gets
relief through visual feedback: view in mirror of
his intact hand unclenching as seen in mirror
box
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FIGURE 10.23 The places on
Tom’s body where touches
elicited sensations in his
phantom hand. (Based on
Ramachandran & Blakeslee,
1998.)
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