Plasticity after brain damage  Both ischemia and hemorrhage lead to

many of the same problems, including

Brain damage and Short term recovery edema (the accumulation of fluid),
which increases pressure on the brain
Possible causes of brain damage: and the probability of additional
strokes.
 Tumors  Both ischemia and hemorrhage also
 Infections impair the sodium-potassium pump,
 Exposure to radiation or toxic leading to an accumulation of sodium
substance inside neurons.
 Degenerative conditions  The combination of edema and excess
 Parkinson’s disease sodium provokes excess release of the
 Alzheimer’s disease transmitter glutamate which
overstimulates neurons: sodium and
In young people, most common cause is other ions enter the neurons faster
closed head injury, a sharp blow to the than the sodium potassium pump can
head resulting from an accident, assault or remove them.
other sudden trauma that does not actually  The excess positive ions block
puncture the brain. metabolism in the mitochondria and
kill the neurons
Closed head injuries are common, and mild  As neurons die, microglia cells
ones produce little or no lasting damage. proliferate, removing the products of
dead neurons and providing
When damage does occur, one cause is the neurotrophins that promote survival of
rotational forces that drive brain tissue the remaining neurons
against the inside of the skull. Another
cause is blood that interrupt blood flow to
the brain.

Reducing the harm from stroke

Common cause of brain damage in older

people is temporary loss of blood flow to a
brain area during a stroke, also known as a
cerebrovascular accident.

Ischemia
 More common type of stroke
 the result of a blood clot or other
obstruction in an artery
 Neurons are deprived of blood and
therefore lose much of their oxygen A. Brain of a person who died immediately
and glucose supply after stroke, note the slwelling on the right
side
Hemorrhage B. Brain of a person who survived for a
 Less common type of stroke long time after a stroke. Note the cavities
 The result of a ruptured artery on the left side where many cells were lost
 They are flooded with blood and C. Brain of a person who suffered a
excess oxygen, calcium, and other gunshot wound and died immediately
chemicals
Immediate treatments

Tissue plasminogen activator (tPA)

 A drugs helps to breaks up blood clots
 A drugs that can treat ischemia
 It has also side effects (sometimes
hemorrhage)

 A patient with stroke should receive

tPA within 3 hours after stroke,
although slight benefits are possible
during next several hours
 It is often difficult to determine
whether is ischemia or hemorrhagic
stroke
 But the usual decision is to give tPA Collateral circulation is a network of
because hemorrhagic worse is small tiny blood vessels, and, under normal
compared to ischemia conditions, not open. When the
coronary arteries narrow to the point
After the first hours
that blood flow to the heart muscle is
Penumbra (Latin word “almost shadow”) limited (coronary artery disease),
 the region surrounding the immediate collateral vessels may enlarge and
damage become active.
 Prevent over stimulation by blocking
glutamate synapses Cannabinoids
 Ischemic penumbra refers to a rim of  Reduce cell loss after stroke, closed
tissue lying just outside the core head injury, and other kinds of
ischemic region (area most severely brain damage
damaged by stroke or ischemic event).  The benefits are apparently due to
Within the core ischemic region, blood
cannaninoids’ antioxidant or anti-
and oxygen flow is severely
inflammatory actions
diminished, resulting in neuronal
death.
 Penumbra stroke can survive at least  Another possibility is injections of
temporally omega-3 fatty acids, like the ones
found in fish oils
 Omega-3fatty acids, which are a major
component of cell membranes, helps
to block apoptosis and other neural
damage

Increased brain stimulation

Effects of brain damage

 Functions of the cells that were
destroyed.
 Activity in any brain area stimulates
many other areas, so damage to any
 areas deprives other areas of their myelin sheath back to the original
normal stimulation and thus target.
interferes with their healthy
functioning.  If the axon is cut instead of crushed,
the myelin on the two sides of the cut
Diaschisis (greek term meaning “to shock may not line up correctly, and the
throughout”) regenerating axon may not have a sure
 Refers to decreased activity of path to follow. Sometimes, a motor
surviving neurons after damage to nerve attaches to the wrong muscle
other neurons
 Diaschisis is a sudden change of  Within a mature mammalian brain or
function in a portion of the brain spinal cord, damaged axons regenerate
connected to a distant, but damaged, only a millimeter or two
brain area.  Therefore, paralysis caused by spinal
cord injury is permanent. However, in
 Stimulant drugs also promote many kinds of fish, axons do
recovery. regenerate across a cut spinal cord far
 Injecting amphetamine significantly enough to restore nearly normal
enhanced both behaviors, and animals functioning.
that practiced the behaviors under the
influence of amphetamine showed  Several problems limit axon
long lasting benefits regeneration in mammals. First, a cut
 Injecting a drug that blocks dopamine in the nervous system causes a scar to
synapses impaired behavioral recovery form (thicker in mammals than in fish),
 Tranquilizers decrease the release of which creates a mechanical barrier.
dopamine and impair recovery after Second, neurons on the two sides of
brain damage the cut pull apart. Third, when glia in
the CNS react to brain damage, they
release chemicals that inhibit axon
The regrowth of Axons growth

 These problems are formidable, but

hope remains. Re- searchers have
developed a way to build a protein
bridge, providing a path for axons to
regenerate across a scar-filled gap.
 Most CNS (neurons in spinal cord) do
not regenerate because the clean up is
slow, oligodendrocytes is inhibit
regeneration, and the environment is
 Although a destroyed cell body cannot not very optimal
be replaced, damaged axons do grow  Neurons in PNS can regenerate
back under certain circumstances. because the clean up is faster because
of microglia, schwaan cells assist in
 A neuron of the peripheral nervous regenerate, and time is of the essence
system has its cell body in the spinal  If cell body is damage it cannot
cord and an axon that extends into one regenerate
of the limbs. If the axon is crushed, the  If damage axon terminalbulbs neurons
degenerated portion grows back can regenerate 1mm per day
toward the periphery at a rate of
about 1 mm per day, following its Sprouting (growing)
 Second, damage sometimes induces
sprouting by unrelated axons.
 The information they bring is certainly
not the same as what was lost. This
kind of sprouting can be useful,
neutral, or harmful.

Collateral sprouting can be defined as the

growth of intact axons into neighboring
denervated territory
 The brain continually adds new
branches of axons and dendrites while Denervation: Loss of nerve supply. Causes
withdrawing old ones. of denervation include disease, chemical
toxicity, physical injury, or intentional
 Brain damage accelerates that process. surgical interruption of a nerve.
After loss of a set of axons, the cells
that lost their source of innervation Denervation Super sensitivity
react by secreting neurotrophins to
induce other axons to form new  A postsynaptic cell that is deprived of
branches, or collateral sprouts, that most of its synaptic inputs develops
attach to the vacant synapses In the increased sensitivity to the
area near the damage, the formation neurotransmitters that it still receives.
of new synapses increases to as much For example, a normal muscle cell
as eight times its usual rate over the responds to the neurotransmitter
next 2 weeks, and it remains above acetylcholine only at the
average 6 weeks after the lesion. neuromuscular junction. If the axon is
cut or if it is inactive for days, the
 Most research has concerned the muscle cell builds additional receptors,
hippocampus, where two types of becoming sensitive to acetylcholine
sprouting are known to occur. First, over a wider area of its surface.
damage to a set of axons induces
sprouting by similar axons.  The same process occurs in neurons.
Heightened sensitivity to a
 Those sprouts form gradually over neurotransmitter after the destruction
weeks, simultaneous with of an incoming axon is known as
improvements in memory task denervation super sensitivity.
performance, and several kinds of Heightened sensitivity as a result of
evidence indicate that sprouting is inactivity by an incoming axon is called
essential for the improvement. disuse super sensitivity. Super
sensitivity results from an increased
number of receptors and increased
effectiveness of receptors, perhaps by
changes in second-messenger
systems.

 Denervation super sensitivity helps

compensate for decreased input. In
some cases, it enables people to
maintain nearly normal behavior even
after losing most of the axons in some
pathway. However, it can also have
 unpleasant consequences, such as
chronic pain. Because spinal injury
damages many axons, postsynaptic
neurons develop increased sensitivity
to the remaining ones. Therefore, even Also consider how the cortex reorganizes
normal input produces enhanced after an amputation. Reexamine Figure
responses. 4.24, Each section along the somatosensory
cortex receives input from a different part
Reorganized Sensory Representations and of the body. Within the area marked
the Phantom Limb “fingers” in that figure, a closer
examination reveals that each subarea
 As described in the first module of this responds more to one finger than to
chapter, experiences can modify the another. Figure 5.16 shows the
connections within the cerebral cortex arrangement for a monkey brain. In one
to increase the representation of study, experimenters amputated finger 3 of
personally important information. an owl monkey. The cortical cells that
Recall that after someone has played a previously responded to information from
string instrument for many years, the that finger lost their input. Soon they
somatosensory cortex has an enlarged became more responsive to finger 2, finger
representation of the fingers of the left 4, or part of the palm, until the cortex
hand. Such changes represent either developed the pattern of responsiveness
collateral sprouting of axons or shown in Figure 5.16
increased receptor sensitivity by the What happens if an entire arm is
postsynaptic neurons. Similar amputated? For many years, neuroscience
processes occur after nervous system assumed that the cortical area
damage. For example, consider what corresponding to that arm would remain
happens after a stroke that damages permanently silent because axons from
the axons bringing information from other cortical areas could not sprout far
the upper left visual field while leaving enough to reach the area representing the
the visual cortex intact. The part of the arm. Then came a surprise. Investigators
visual cortex responding to the lower recorded from the cerebral cortices of
left visual field still gets its normal monkeys whose sensory nerves from one
input. Gradually, axons representing forelimb had been cut 12 years previously.
the lower left field sprout into the They found that the stretch of cortex
vacated synapses representing the previously responsive to the limb was now
upper field. As that happens, a responsive to the face.
stimulus that should look as shown
here on the left begins to look like the After loss of sensory input from the
stimulus on the right: forelimb, the axons representing the
forelimb degenerated, leaving vacant
synaptic sites at several levels of the CNS.
Evidently, axons representing the face
sprouted into those sites in the spinal cord,
brainstem, and thalamus. (Or perhaps Evidently, the representation of the genitals
axons from the face were already present had spread into the cortical area
but became stronger through denervation responsible for foot sensation. Is there any
super sensitivity.) Brain scan studies way to relieve a painful phantom
confirm that the same processes occur with sensation? In some cases, yes. Amputees
humans. Now consider what happens when who learn to use an artificial arm report
cells in a re- organized cortex become that their phantom sensations gradually
activated. Previously, those neurons disappear. They start attributing sensations
responded to arm stimulation, and now to the artificial arm, and in doing so, they
they receive information from the face. displace abnormal connections from the
Does the response feel like stimulation on face. Similarly, a study of one man found
the face or on the arm? The answer: It feels that after his hands were amputated, the
like the arm. Physicians have long noted area of his cortex that usually responds to
that many people with amputations the hands partly shifted to face sensitivity,
experience a phantom limb, a continuing but after he received hand transplants, his
sensation of an amputated body part. That cortex gradually shifted back to hand
experience can range from occasional sensitivity.
tingling to intense pain. It is possible to
have a phantom hand, foot, or anything Learned Adjustments in Behavior
else that has been amputated. The
phantom sensation might fade within days So far, the discussion has focused on
or weeks, but sometimes, it lasts a lifetime. anatomical changes. In fact, much recovery
Until the 1990s, no one knew what caused from brain damage is based on learning.
phantom pains, and most believed that the Similarly, someone with brain damage who
sensations were coming from the stump of seems to have lost an ability may indeed
the amputated limb. Some physicians even have lost it or may be able to find it with
performed additional amputations, enough effort. Much, probably most,
removing more and more of the limb in a recovery from brain damage depends on
futile attempt to eliminate the phantom learning to make better use of the abilities
sensations. Modern methods have that were spared. Sometimes, a person or
demonstrated that phantom limbs develop animal with brain damage appears unable
only if the relevant portion of the to do something but is in fact not trying.
somatosensory cortex reorganizes and We say the limb is differentiated because it
becomes responsive to alternative inputs. has lost its afferent (sensory) input. A
For example, axons representing the face monkey with a deafferented limb does not
may come to activate the cortical area spontaneously use it for walking, picking up
previously devoted to an amputated hand. objects, or any other voluntary behaviors.
Whenever the face is touched, the person
still feels the facial sensation but also feels
a sensation in the phantom hand. It is
possible to map out which part of the face
stimulates sensation in which part of the
phantom hand, as shown in Figure 5.17.
Note in Figure 4.24 on page 101 that the
part of the cortex responsive to the feet is
adjacent to the part responsive to the
genitals. Two patients with foot
amputations felt a phantom foot during
sexual arousal! One reported feeling
orgasm in the phantom foot as well as the
genitals—and enjoyed it intensely.
Cross section through the spinal cord

Investigators initially assumed that the

monkey could not use a limb that it didn’t
feel. In a later experiment, however, they
cut the afferent nerves of both forelimbs.
Despite this more extensive damage, the
monkey used its deafferented limbs to
walk, climb the walls of metal cages, and
pick up raisins. Apparently, a monkey fails
to use a deafferented forelimb only
because walking on three limbs is easier
than using the impaired limb. When it has
no choice but to use its deafferented limbs,
it does.

Similarly, many people with brain damage

find ways of getting through the tasks of
their day without relying on their impaired
skills. Therapists get their best results if they start
soon after a patient’s stroke, and animal
Therapy for people with brain damage researchers find the same pattern. In one
focuses on encouraging them to practice study, rats with damage to the parietal
skills that are impaired but not lost. cortex of one hemisphere showed poor
Treatment begins with careful evaluation of coordination of the contralateral forepaw.
a patient’s abilities and disabilities. Such Some of the rats received experiences
evaluations are the specialty of designed to encourage them to use the
neuropsychologists. For example, someone impaired limb.
who has trouble carrying out spoken
instructions might be impaired in hearing, Those who began practice 5 days after the
memory, language, muscle control, or damage recovered better than those who
alertness. After identifying the problem, a started after 14 days, who in turn
neuropsychologist might refer a patient to a recovered better than those who started
physical therapist or occupational therapist, after 30 days. As other kinds of evidence
who helps the patient practice the impaired have confirmed, the brain has increased
skills. plasticity during the first days after damage.

One important generalization is that

behavior recovered after brain damage is
effortful, and the recovery is precarious. A
person with brain damage who appears to
be functioning normally is working harder
than usual. The recovered behavior
deteriorates markedly after drinking
alcohol, physical exhaustion, or other kinds
of stress that would minimally affect most
other people. It also deteriorates more than
average in old age.