Transcript Topic 10 Brain Damage and Neuroplasticity

Topic 10
Brain Damage and Neuroplasticity
Can the Brain Recover from Damage?
Causes of Brain Damage
 Brain tumors
 Cerebrovascular disorders
 Closed-head injuries
 Infections of the brain
 Neurotoxins
 Genetic factors
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
Brain Tumors
 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
Cerebrovascular Disorders
 Stroke – a sudden-onset cerebrovascular event
that causes brain damage
 Cerebral hemorrhage – bleeding in the brain
 Cerebral ischemia – disruption of blood supply
 3rd leading cause of death in the US and most
common cause of adult disability
Cerebrovascular Disorders
 Cerebral hemorrhage – blood vessel ruptures
 Aneurysm – a weakened point in a blood vessel that makes a
stroke more likely. May be congenital or due to poison or
infection.
 Congenital – present at birth
 Cerebral ischemia – disruption of blood supply
 Thrombosis – plug forms
 Embolism – plug forms elsewhere and moves to the brain
 Arteriosclerosis – wall of blood vessels thicken, usually due to
fat deposits
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 Ca++
Damage due to Cerebral Ischemia
 lnflux of Na+ and Ca++ 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
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. A
hematoma, a bruise, forms.
 Concussion – when there is a disturbance of
consciousness following a blow to the head and no
evidence of structural damage.
Concussions
 While there is no apparent brain damage
with a single concussion, multiple
concussions may result in a dementia
referred to as “punch-drunk syndrome”
 When might this occur?
 Can it be prevented?
Brain Infection
 Invasion of the brain by microorganisms
 Encephalitis – the resulting inflammation
 Bacterial infections
 Often leads to abscesses, pockets of pus
 May inflame meninges, creating meningitis
 Treat with penicillin and other antibiotics
 Viral infections
 Some viral infections preferentially attack neural tissues
Brain Infections - Some Causes
 Bacterial
 Viral
 Syphilis – may produce a
 Rabies – high affinity for the
syndrome of insanity and
dementia known as general
paresis
 Syphilis bacteria are passed to
the noninfected and enter a
dormant stage for many
years.
nervous system
 Mumps and herpes –
typically attack tissues other
than the brain
 Viruses may lie dormant for
years
Neurotoxins
 May enter general circulation from the GI tract, lungs, or
through the skin
 Toxic psychosis – chronic insanity produced by a neurotoxin.
 The Mad Hatter – may have had toxic psychosis due to
mercury exposure
Neurotoxins
 Some antipyschotic drugs produce a motor
disorder caused tardive dyskinesia
 Recreational drugs, such as alcohol, may cause
brain damage
 Neurotoxic effects of alcohol
 Thiamine deficiency
 Some neurotoxins are endogenous – produced by
the body
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
 Characteristic disfigurement, mental retardation, other
health problems
Autistic Disorder
 A chronic disorder whose symptoms include failure to
develop normal social relations with other people,
impaired development of communicative ability, lack
of imaginative ability, and repetitive, stereotypical
movements.
Possible causes
 Biological
Autism was once believed to be acquired through interactions with
hostile, withdrawn parents.
Research and mental health professionals are convinced autism is
caused by biological factors.
Between 2 and 3 percent of siblings of people with autism are
themselves autistic.
There is a 70 percent concordance rate for monozygotic twins.
Possible causes
 Phenylketonuria (PKU)
A hereditary disorder caused by the absence of an enzyme that converts
the amino acid phenylalanine to tyrosine; causes brain damage unless a
special diet is implemented soon after birth.
 Brain pathology
•Heritable aspect of autism suggests the disorder is a result of structural or
biochemical abnormalities in the brain.
•Researchers have found evidence for structural abnormalities in the brains
of autistics, but so far we cannot point to any single abnormality as the
cause of the disorder.
Attention-Deficit/Hyperactivity
Disorder
 A disorder characterized by uninhibited responses, lack of
sustained attention, and hyperactivity; first shows itself in
childhood.
 ADHD is the most common behavior disorder that shows
itself in childhood.
 ADHD is seen in 4 to 5% of grade school children.
Possible causes
 Genetics
There is strong evidence from family and twin studies for hereditary factors in a
person’s likelihood of developing ADHD.
 Learning
Some evidence suggests impulsive and hyperactive behaviors are a result of a
steep delay of reinforcement gradient.
Possible causes
 Biological
There is evidence to suggest that abnormalities in dopaminergic transmission
play a role in ADHD.
 Brain structures
Studies of brain structure of people with ADHD do not reveal any
localized abnormalities, though the total volume of their brains is
approximately 4% smaller than normal.
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
Epilepsy
 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
 Diagnosis
 EEG – Electroencephalogram
 Seizures associated with high amplitude spikes
Epilepsy
 Seizures often preceded by an aura, such as a
smell, hallucination, or feeling
 Aura’s nature suggests the epileptic focus
 Warns epileptic of an impending seizure
 Partial epilepsy – does not involve the whole
brain
 Generalized epilepsy – involve the entire brain
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
Generalized Seizures
 Grand mal
 Loss of consciousness and equilibrium
 Tonic-clonic convulsions
 -rigidity (tonus) and 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
Parkinson’s Disease
 A movement disorder of middle and old age
affecting ~ .5%of the population
 Pain and depression commonly seen before the
full disorder develops
 Tremor at rest is the most common symptom of
the full-blown disorder
 Dementia is not typically seen
 No single cause
Parkinson’s Disease
 Associated with degeneration of the substantia
nigra whose neurons use dopamine
 Almost no dopamine in the substantia nigra of
Parkinson’s patients
 Treated temporarily with L-dopa
 Linked to ~10 different gene mutations
Huntington’s Disease
 Also a progressive motor disorder of middle and old age
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– but rare, with a strong genetic basis, and associated
with dementia.
Begins with fidgetiness and progresses to jerky
movements of entire limbs and sever dementia
Death usually occurs within 15 years
Caused by a single dominant gene
1st symptoms usually not seen until age 40
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)
Multiple Sclerosis
 Epidemiological studies find that incidence of MS is
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increased in those who spend childhood in a cool climate
MS is rare amongst Africans and Asians
Strong genetic predisposition and many genes involved
An autoimmune disorder – immune system attacks
myelin
Drugs may retard progression or block some symptoms
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
Neuropsychological Diseases - Recap
 Epilepsy – abnormal electrical activity
 Parkinson’s disease
 progressive motor disorder without dementia
 Huntington’s disease
 progressive motor disorder with dementia
 Multiple sclerosis
 autoimmune disorder that affects motor function and strikes
early
 Alzheimer’s disease - dementia
Animal Models of Human
Neuropsychological Diseases
 While animal models only model some aspects of the
human condition, they can provide insight
 Kindling model of epilepsy
 Experimentally induced seizure activity
 Transgenic mouse model of Alzheimer’s
 Mice producing human amyloid
 MPTP model of Parkinson’s
 Drug-induced damage comparable to that seen in PD
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
 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
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
Neuroplastic Responses to Nervous
System Damage
 Degeneration - deterioration
 Regeneration – regrowth of damaged neurons
 Reorganization
 Recovery
Degeneration
 Cutting axons is a common way to study responses to neuronal
damage
 Anterograde - degeneration of the distal segment – between the
cut and synaptic terminal
 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
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
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
Neural Reorganization
 Reorganization of 1° sensory and motor systems has
been observed following damage to:
 peripheral nerves
 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 scale of reorganization possible is far
greater than anyone assumed possible
How/why does damage lead to
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
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 new ways
 Adult neurogenesis may play a role in recovery
Treating Nervous System Damage
 Reducing brain damage by blocking neurodegeneration
 Promoting recovery by promoting regeneration
 Promoting recovery by transplantation
 Promoting recovery by rehabilitative training
Reducing brain damage by blocking
neurodegeneration
 Various neurochemicals can block or limit
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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
Promoting Recovery by Promoting
Regeneration
 While regeneration does not normally occur in the CNS,
experimentally it can be induced
 Eliminate inhibition of oligodendroglia and regeneration can
occur
 Provide Schwann cells to direct growth
Promoting Recovery by
Neurotransplantation
 Fetal tissue
 Fetal substantia nigra cells used to treat MPTP-treated
monkeys (PD model)
 Treatment was successful
 Limited success with humans
 Stem cells
 Rats with spinal damage “cured”, but much more
research is needed
Promoting Recovery by Rehabilitative
Training
 Constraint-induced therapy – down functioning limb while
training the impaired one – create a competitive situation to
foster recovery
 Facilitated walking as an approach to treating spinal injury
Can the brain recover from brain
damage?
 Consider what you now know about the
brain’s ability to adapt following brain
damage, can it “recover”?
 If so, what conditions promote
recovery?