Chapter 12
The Central Nervous System
463
12
stimulated neuron. Afer brain injury, neurons totally deprived
oF oxygen begin to disintegrate, unleashing the cellular equiva-
lent oF “buckets” oF glutamate. Under these conditions, gluta-
mate acts as an
excitotoxin
, literally exciting surrounding cells
to death.
Te initial events in excitotoxicity are identical to those in
L±P: Ca
2
1
flows in through NMDA receptor channels (see
p. 458). In excitotoxicity, however, the amount oF Ca
2
1
swamps
the cell’s ability to cope and Ca
2
1
homeostasis breaks down.
High levels oF Ca
2
1
kill cells in two ways:
Ca
2
1
damages mitochondria, causing them to produce the
Free radical superoxide, which damages cells directly and can
also cause programmed cell death (apoptosis).
Ca
2
1
turns on the synthesis oF certain proteins. Some oF these
promote apoptosis while others are enzymes that produce
the Free radical NO and other powerFul inflammatory agents.
Although the NMDA receptor and the enzyme that makes
NO are attractive targets For drug therapies to decrease damage
around the stroke epicenter, clinical trials so Far have all Failed.
At present, the most successFul treatment For stroke is tissue
plasminogen activator (tPA), which dissolves blood clots in the
brain. Alternatively, a mechanical device can drill into a blood
clot and pull it From a blood vessel like a cork From a bottle.
Other approaches currently under study Focus on recovering
Function afer a stroke. One method implants immature neurons
into stroke-damaged brain regions in the hope that they will take
on properties oF nearby mature neurons. Another tries to coax
adult brain stem cells to replace damaged neurons. Mice with
strokes can generate new tissue and recover motor Function when
treated with a combination oF growth Factors during a critical
time Following injury. HopeFully, this will be true For humans, too.
Degenerative Brain Disorders
Alzheimer’s Disease
Alzheimer’s disease (AD)
(altz
9
hi-merz), a progressive de-
generative disease oF the brain, ultimately results in
dementia
(mental deterioration). Alzheimer’s patients represent nearly
halF oF the people living in nursing homes. Between 5 and 15%
oF people over 65 develop this condition, and For up to halF oF
those over 85 it is a major contributing cause in their deaths.
Its victims exhibit memory loss (particularly For recent
events), shortened attention span, disorientation, and eventual
language loss. Over a period oF several years, Formerly good-
natured people may become irritable, moody, and conFused.
Hallucinations may ultimately occur.
Examinations oF brain tissue reveal senile plaques littering
the brain like shrapnel between the neurons. Te plaques con-
sist oF extracellular aggregations oF
beta-amyloid peptide
, which
is cut From a normal membrane precursor protein (APP) by
enzymes. One Form oF Alzheimer’s disease is caused by an in-
herited mutation in the gene For APP, which suggests that too
much beta-amyloid may be toxic. New evidence suggests that
the beta-amyloid peptide may exert its toxic effect through the
prion protein, the same protein that (in an altered Form) causes
brain stem contusions always cause coma, lasting From hours to a
liFetime because oF injury to the reticular activating system.
²ollowing a head blow, death may result From
subdural
or
subarachnoid hemorrhage
(bleeding From ruptured vessels
into those spaces). Individuals who are initially lucid and then
begin to deteriorate neurologically are, in all probability, hem-
orrhaging intracranially. Blood accumulating in the skull in-
creases intracranial pressure and compresses brain tissue. IF the
pressure Forces the brain stem inFeriorly through the Foramen
magnum, control oF blood pressure, heart rate, and respiration
is lost. Intracranial hemorrhages are treated by surgically re-
moving the hematoma (localized blood mass) and repairing the
ruptured vessels.
Another consequence oF traumatic head injury is
cerebral
edema
, swelling oF the brain. At best, cerebral edema aggravates
the injury. At worst, it can be Fatal in and oF itselF.
Cerebrovascular Accidents (CVAs)
Te single most common nervous system disorder and the third
leading cause oF death in North America are
cerebrovascular
accidents (CVAs)
(ser
0
ĕ-bro-vas
9
ku-lar), also called
strokes
or
“brain attacks.” CVAs occur when blood circulation to a brain
area is blocked and brain tissue dies. [
Ischemia
(is-ke
9
me-ah;
“to hold back blood”), deprivation oF blood supply to any tissue,
impairs the delivery oF oxygen and nutrients to cells.]
Te most common cause oF CVA is a blood clot that blocks
a cerebral artery. A clot can originate outside the brain (From
the heart, For example) or Form on the roughened interior wall
oF a brain artery narrowed by atherosclerosis. Less Frequently,
strokes are caused by bleeding, which compresses brain tissue.
Tose who survive a CVA are typically paralyzed on one side
oF the body (
hemiplegia
). Many exhibit sensory deficits or have
difficulty understanding or vocalizing speech. Even so, the pic-
ture is not hopeless. Some patients recover at least part oF their
lost Faculties, because undamaged neurons sprout new branches
that spread into the injured area and take over some lost Func-
tions. Physical therapy should start as soon as possible to pre-
vent muscle contractures (abnormally shortened muscles due to
differences in strength between opposing muscle groups).
Not all strokes are “completed.” ±emporary episodes oF re-
versible cerebral ischemia, called
transient ischemic attacks
(TIAs)
, are common. ±IAs last From 5 to 50 minutes and are
characterized by temporary numbness, paralysis, or impaired
speech. Tese deficits are not permanent, but ±IAs do constitute
“red flags” that warn oF impending, more serious CVAs.
A CVA is like an undersea earthquake. It’s not the initial tem-
blor that does most oF the damage, it’s the tsunami that floods
the coast later. Similarly, the initial vascular blockage during a
stroke is not usually disastrous because there are many blood
vessels in the brain that can pick up the slack. Rather, it’s the
neuron-killing events outside the initial ischemic zone that
wreak the most havoc.
Experimental evidence indicates that the main culprit is
glutamate
, an excitatory neurotransmitter also involved in
learning and memory. Normally, glutamate binding to NMDA
receptors opens NMDA channels that allow Ca
2
1
to enter the
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