Fakhrurrazy

 Brain tumors
 Cerebrovascular disorders
 Closed-head injuries
 Infections of the brain
 Neurotoxins
 Genetic factors
 A tumor (neoplasm) is a mass of cells that
grows independently of the rest of the
body: a cancer.
 20 percent of brain tumors are
meningiomas—that is, encased in
meninges.
◦ Encapsulated; growing within their own
membranes
◦ Usually benign; surgically removable
 Most brain tumors are infiltrating.
Grow diffusely through surrounding tissue
Malignant; difficult to remove or destroy
 About 10 percent of brain tumors are
metastatic; they originate elsewhere,
usually the lungs.
FIGURE 10.1 A meningioma.
FIGURE 10.3 An MRI of Professor
P.’s acoustic neuroma. The arrow
indicates the tumor.
 Stroke: a sudden-onset cerebrovascular
event that causes brain damage
Cerebral hemorrhage: bleeding in the brain
Cerebral ischemia: disruption of blood supply
 Stroke is the third leading cause of death
in the U.S. and the most common cause of
adult disability.
 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
FIGURE 10.4 An angiogram that
illustrates narrowing of the
carotid artery (see arrow), the
main pathway of blood to the
brain.
 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+.
 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
The mechanisms of damage vary with the brain
structure affected.
FIGURE 10.5 The cascade of
events by which the stroke-
induced release of glutamate
kills neurons.
 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: a disturbance of
consciousness following a blow to the
head and no evidence of structural
damage
 While there is no apparent brain damage
with a single concussion, multiple
concussions may result in a dementia
referred to as “punch-drunk syndrome.”
FIGURE 10.6 A CT scan of a
subdural hematoma. Notice
that the subdural hematoma
has displaced the left lateral
ventricle.
 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.
 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 in 18th- and
19th-century England often had toxic
psychosis due to mercury exposure.
 Some antipsychotic drugs produce a
motor disorder called tardive dyskinesia.
 Some neurotoxins are endogenous
(produced by the body).
E.g., auto-immune disorders
 Most neuropsychological diseases of genetic
origin are associated with recessive genes.
Why?
 Down Syndrome
Down syndrome occurs in 0.15 percent of births;
probability increases with advancing maternal age.
An extra chromosome 21 is created during
ovulation.
Characteristic disfigurement, mental retardation,
other health problems
 All six causes of brain damage produce
damage, in part, by activating apoptosis.
 Epilepsy
 Parkinson’s disease
 Huntington’s disease
 Multiple sclerosis
 Alzheimer’s disease
 The primary symptom is seizures, but not
all who have seizures have epilepsy.
 Epileptics have seizures generated by
their own brain dysfunction.
 Epilepsy affects about 1 percent of the
population.
 It is difficult to diagnose due to the
diversity and complexity of epileptic
seizures.
 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 are associated with high amplitude
spikes.

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 Seizures are often preceded by an aura, such
as a smell, hallucination, or feeling.
◦ The aura’s nature suggests the epileptic focus.
◦ The aura warns the epileptic of an impending
seizure.
 Partial epilepsy: does not involve the whole
brain
 Generalized epilepsy: involves the entire brain
 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.
 Grand Mal
Loss of consciousness and equilibrium
Tonic-clonic convulsions
 Rigidity (tonus)
 Tremors (clonus)
The resulting hypoxia may cause brain
damage.
 Petit Mal
Not associated with convulsions
A disruption of consciousness associated with
a cessation of ongoing behavior
FIGURE 10.7 Cortical EEG recorded during epileptic
attacks. Notice that each trace is characterized by
epileptic spikes (sudden, high-amplitude EEG signals
that accompany epileptic attacks).
 Parkinson’s is a movement disorder of
middle and old age affecting about 0.5
percent of the population.
 Tremor at rest is the most common
symptom of the full-blown disorder.
 Dementia is not typically seen.
 No Single Cause
 Parkinson’s is associated with
degeneration of the substantia nigra;
these neurons release dopamine to the
striatum of the basal ganglia.
 There is almost no dopamine in the
substantia nigra of Parkinson’s patients.
 Autopsies often reveal Lewy bodies (protein
clumps) in the substantia nigra.
 Parkinson’s disease can be treated
temporarily with L-dopa.
 Parkinson’s is linked to about ten different
gene mutations.
 Deep brain stimulation of subthalamic
nucleus reduces symptoms, but its
effectiveness slowly declines over months
or years.
 Huntington’s disease is a rare, progressive
motor disorder of middle and old age with
a strong genetic basis.
◦ Huntingtin gene
 Single, dominant gene
 Huntington’s disease begins with
fidgetiness and progresses to jerky
movements of entire limbs and severe
dementia.
 Death usually occurs within 15 years.
 It is caused by a single dominant gene.
 First symptoms are usually not seen until
age 40.
 MS is a progressive disease that attacks
CNS myelin, leaving areas of hard scar
tissue (sclerosis).
 The 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).
 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 have been linked
to MS with any certainty.
 Recent Focus on Epigenetic Mechanisms
◦ Gene–environment interactions
 An autoimmune disorder: the immune
system attacks myelin.
 Drugs may retard progression or block
some symptoms.
FIGURE 10.10 Areas of sclerosis (see arrows)
in the white matter of a patient with MS.
 Alzheimer’s is the most common cause of
dementia; one’s likelihood of developing
it increases with age.
 Alzheimer’s disease is progressive; early
stages are characterized by confusion and
a selective decline in memory.
 Definitive diagnosis is only possible at
autopsy; one must observe neurofibrillary
tangles and amyloid plaques.
 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 the amyloid
hypothesis (amyloid first).
 Decline in acetylcholine levels is one of the
earliest signs of AD.
 Effective treatments are not yet available.
FIGURE 10.11 Amyloid plaques (stained
blue) in the brain of a deceased patient who
had Alzheimer’s disease.
FIGURE 10.12 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.)
 Experiments regarding neuropathology are not
usually possible with human subjects.
 Animal models are often utilized. For example:
 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
 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.
 Only humans and a few related primates
develop amyloid plaques.
 Transgenic: genes of another species have
been introduced
 Genes accelerating human amyloid synthesis
are introduced into mice.
Plaque distribution comparable to that in AD
Unlike humans, no neurofibrillary tangles
 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 provide the means to
identify potentially useful treatments for
PD.
 Adalah kemampuan otak untuk berubah, baik atau
buruk, selama masa kehidupan individu
 Melibatkan pembentukan koneksi neural sebagai
respon terhadap informasi yang berasal dari stimulasi
sensorik dari lingkungan dan perkembangan normal
(Doidge, 2007; Merzenich, 2001; Nudo, 2008).

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 Struktur otak dan saraf yang dipahat yang merupakan
hasil dari jalur saraf dan sinaps, perubahan ini dapat
menyebabkan perubahan sifat, lingkungan dan proses
saraf serta perubahan dari cedera tubuh
 Otak berubah selama masa kehidupan

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 Degeneration: deterioration
 Regeneration: regrowth of damaged neurons
 Reorganization
 Recovery
 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 the regenerating axon
makes a new synaptic contact, the neuron may
survive.
FIGURE 10.13 Neuronal
and transneuronal
degeneration following
axotomy.
 Does not proceed successfully in mammals
and other higher vertebrates: the 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.
 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.
FIGURE 10.14 Three patterns of
axonal regeneration in
mammalian peripheral nerves.
 CNS neurons can regenerate if transplanted
into the PNS, whereas PNS neurons won’t
regenerate in the CNS.
 Schwann cells promote regeneration.
◦ Neurotrophic factors stimulate growth.
◦ CAMs provide a pathway.
 Oligodendroglia actively inhibit
regeneration.
 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 the
lesioned area now respond to an adjacent area.
Remapping occurs within minutes.
 Studies show that large-scale reorganization is
possible.
FIGURE 10.16 Reorganization of the rat motor
cortex following transection of the motor
neurons that control movements of the
vibrissae. The motor cortex was mapped by
brain stimulation before transection and then
again a few weeks after. (Based on Sanes et
al., 1990).
 Brain-imaging studies indicate that there is
continuous competition for cortical space
by functional circuits.
E.g., auditory and somatosensory input may be
processed in formerly visual areas of the brains
of blinded individuals.
 Are existing connections strengthened due
to a release from inhibition?
Consistent with speed and localized nature of
reorganization
 Are new connections established?
Magnitude can be too great to be explained by
changes in existing connections.
 It is difficult to conduct controlled
experiments on populations of brain-
damaged patients.
 Researchers can’t distinguish between true
recovery and compensatory changes.
 Cognitive reserve—education and
intelligence—is thought to play an important
role in recovery of function; this may permit
cognitive tasks to be accomplished in new
ways.
 Adult neurogenesis may play a role in
recovery.
FIGURE 10.18 Increased neurogenesis in the dentate gyrus following damage. The left panel
shows (1) an electrolytic lesion in the dentate gyrus (damaged neurons are stained
turquoise) and (2) the resulting increase in the formation of new cells (stained red), many of
which develop into mature neurons (stained dark blue). The right panel displays the
comparable control area in the unlesioned hemisphere, showing the normal number of new
cells (stained red). (These images are courtesy of my friends Carl Ernst and Brian Christie,
Department of
Psychology, University of British Columbia.)
 Reducing Brain Damage by Blocking
Neurodegeneration
 Promoting Recovery by Promoting
Regeneration
 Promoting Recovery by Transplantation
 Promoting Recovery by Rehabilitative
Training
 Various neurochemicals can block or limit
neurodegeneration.
Apoptosis inhibitor protein: introduced in rats via a
virus
Neurotrophic factors (BDNF, GDNF) block
degeneration of damaged neurons.
 Neuroprotective molecules also tend to
promote regeneration.
 While regeneration does not normally
occur in the CNS, it can be induced
experimentally by directing the growth of
axons by Schwann cells.
 Transplanting Fetal Tissue
Fetal substantia nigra cells were 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 showed improved
mobility.
 Monkeys recovered hand function from
induced strokes following rehab training.
 Constraint-induced therapy in stroke
patients—tying down the functioning limb
while training the impaired one—creates a
competitive situation to foster recovery.
 Facilitated Walking as an Approach to
Treating Spinal Injury
 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 the rodent hippocampus.
 Ramachandran’s hypothesis: phantom limb
is caused by reorganization of the somato-
sensory cortex following amputation.
 The amputee feels a touch on his face and
also on his phantom limb (due to their
proximity on somatosensory cortex).
 An amputee with chronic phantom limb
pain gets relief through visual feedback:
view in mirror of her intact hand
unclenching, as seen in mirror box.
FIGURE 10.20 The places on
Tom’s body where touches
elicited sensations in his
phantom hand. (Based on
Ramachandran & Blakeslee,
1998.)