Text 1

A Closer Look at Exercise Physiology

What is Exercise Physiology?

Exercise physiology is the study of both the functional changes that

occur in response to a single session of exercise and the adaptations that occur
as a result of regular, repeated exercise sessions. Exercise initially disrupts
homeostasis. The changes that occur in response to exercise are the bodys
attempt to meet the challenge of maintaining homeostasis when increased
demands are placed on the body. Exercise often requires prolonged coordination
among most body systems, including the muscular, skeletal, nervous,
circulatory, respiratory, urinary, integumentary (skin), and endocrine (hormone-
producing) systems.
Heart rate is one of the easiest factors to monitor that shows both an
immediate response to exercise and long-term adaptation to a regular exercise
program. When a person begins to exercise, the active muscle cells use more O 2
to support their increased energy demands. Heart rate increases to deliver more
oxygenated blood to the exercising muscles. The heart adapts to regular exercise
of sufficient intensity and duration by increasing its strength and efficiency so
that it pumps more blood per beat. Because of increased pumping ability, the
heart does not have to beats as rapidly to pump a given quantity of blood as it
did before physical training.
Exercise physiologists study the mechanisms responsible for the changes
that occur as a result of exercise. Much of the knowledge gained from the study
of exercise is used to develop appropriate exercise programs to increase the
functional capacities of people ranging from athletes to the infirm. The
importance of proper and sufficient exercise in disease prevention and
rehabilitation is becoming increasingly evident.

1
 Text 2
A Closer Look at Exercise Physiology
Aerobic exercise: What For and How Much?

Aerobic (with O2) exercise involves large muscle groups and is performed
at a low-enough intensity and for a long-enough period of time that fuel sources can
be converted to ATP by using the citric acid cycle and electron transport chain as the
predominant metabolic pathway. Aerobic exercise can be sustained for from 15 to 20
minutes to several hours at a time. Short-duration, high-intensity activities such as
weight training and the 100 meter dash, which last for a matter of seconds and rely
solely on energy stored in the muscles and on glycolysis, are forms of anaerobic
(without O2) exercise.
Inactivity is associated with increased risk of developing both hypertension
(high blood pressure) and coronary artery disease (block-age of the arteries that supply
the heart). The American College of Sports Medicine recommends that an individual
participate in aerobic exercise a minimum of three times per week for 20 to 60
minutes to reduce the risk of hypertension and coronary artery disease and to improve
physical work capacity. Recent studies have shown the same health benefits are
derived whether the exercise is accomplished in one long stretch or is broken down
into multiple shorter stints. This is good news, because many individuals find it easier
to stick with brief bouts of exercise sprinkled throughout the day.
The intensity of exercise should be based on a percentage of the individuals
maximal capacity to work. The easiest way to establish the proper intensity of exercise
and to monitor intensity levels is by checking the heart rate. The estimated maximal
heart rate is determined by subtracting the persons age from 220. Significant benefits
can be derived from aerobic exercise performed between 70% and 80% of maximal
heart rate. For example, the estimated maximal heart rate for a 20 year old is 200 beats
per minute. If this person exercised three times per week for 20 to 60 minutes at an
intensity that increased the heart rate to 140 to 160 beats per minute, the participant
should significantly improve his or her aerobic work capacity and reduce the risk of
cardiovascular disease.

2
 Text 3
cells. In the type 1 form A
of Closer
the disease,
Look not enough insulin
at Exercise is produced to meet
Physiology
the bodys need for glucose uptake.
Exercising Regular
Muscles Haveaerobic exercise
a Sweet Toothreduces the
amount of insulin that must be injected to promote glucose uptake and reduce
During exercise,
the blood glucosemuscle cells use
level toward more In
normal. glucose and2other
the Type formnutrient fuels than
of the disease,
usual
insulintoispower their but
produced, increased contractile
insulins activity.
target cells The rate ofsensitivity
have decreased glucose transport
to its
into exercising
presence. muscle may
By increasing the increase more than 10-fold
cells responsiveness to the during
insulinmoderate
available,or
intense physicalexercise
regular aerobic activity.helps
Glucose uptake
drive by into
glucose cellsthe
is accomplished
cells, where itby
canglucose
be used
carriers in the
for energy plasma membrane.
production, Cells maintain
instead of remaining in theanplasma,
intracellular
wherepool of to
it leads
additional
detrimentalcarriers that canfor
consequences be the
inserted
body.into the plasma membrane as the need for
glucose uptake increases. In many cells, including resting muscle cells,
facilitated diffusion of glucose into the cells depends on the hormone insulin.
Insulin promotes the insertion of glucose carriers in the plasma membranes of
insulin-dependent cells. Because plasma insulin levels fall during exercise,
however, insulin is not responsible of the increased transport of glucose into
exercising muscles. Researchers have shown instead that muscle cells insert
more glucose carriers in their plasma membranes in response to exercise. This
has been demonstrated in rats that have undergone physical training.
Exercise influences glucose transport into cells in yet another way.
Regular aerobic exercise (see p.37) has been shown to increase both the affinity
(degree of attraction) and number of plasma membrane receptor sites that bind
specifically with insulin. This adaptation results in an increase in insulin
sensitivity; that is, the cells are more responsive than normal to a given level of
circulating insulin.
Because insulin enhances the facilitated diffusion of glucose into most
cells, an exercise-induced increase in insulin sensitivity is one of the factors that
makes exercise a beneficial therapy for controlling diabetes mellitus. In this
disorder, glucose entry into most cells is impaired as a result of inadequate
insulin action (see chapter 19). Plasma levels of glucose become elevated
because glucose remains in the plasma instead of being transported into the

43
 Text 4
As painful as this lesson was,
Concepts, scientists and
Challenges, started over, preparing new cell lines
Controversies
and using new, stricter
HeLarules ofProblems
Cells: technique in
to aprevent contamination
Growing Industry with HeLa
cells. Unfortunately, the problem did not end. In 1974, Walter Nelson-Rees
published
Many basica paper demonstrating
advances that 5 cell
in cell physiology, lines extensively
genetics, and cancerused in cancer
research have come
research were in
about through thefact
useall
of HeLa cells. Inor1976,
cells grown, 11 additional
cultured, cell
outside the lines,Ineach
body. widely
the middle
used
of theinlast
research,
century,were
manyalso found to
attempts be HeLa
were made cells; and in
to culture 1981,cells
human Nelson-Rees listed
using tissues
22 more cell
obtained fromlines that were
biopsies contaminated
or surgical withThese
procedures. HeLa.early
In all,attempts
one third of all met
usually cell
lines used in the
with failure; cancer
cellsresearch were
died after apparently
a few days or really
weeksHeLa cells.mostly
in culture, The result was an
without
enormous
undergoingwaste of dollars and
cell replication. resources.
These difficulties continued until February 1951, when
The invasion
a researcher at Johns of other cultures
Hopkins by HeLa
University cellsa sample
received is a testament to thecancer
of cervical ferocious
from
and aggressive
a patient namednature of some
Henrietta cancer
Lacks. cells. In
Following cell-culturethe
convention, laboratories,
culture wasrules
nameof
sterile
HeLa by technique are the
combining supposed to ensure
first two that
letters of thecross-contamination ofnames.
donors first and last one culture
This
with another
cell line doesgrew
not only not occur. But researchers
but prospered are only
under culture human, and
conditions andthey sometimes
represented one
make
of the mistakes. Forlines
earliest cell example, perhapsgrown
successfully a bottle of culture
outside medium was contaminated
the body.
throughResearchers
improper handling. Whatever
were eager to havethe case cells
human clearly at someon
available point one or
demand tomore
study
HeLa cells of
the effects were introduced
drugs, into cultures
toxic chemicals, where and
radiation, theyviruses
did noton
belong.
human tissue. For
HeLa
example, cells divide
poliomyelitis more
virus rapidly than
reproduced wellmost othercells,
in HeLa human cells, whether
providing a
normal or cancerous.
breakthrough Because of their
in the development rapid
of polio growthAs
vaccine. andcell-culture
division, they use up the
techniques
nutrients
improved,more quickly
human than were
cell lines otherstarted
cell types.
fromWhats more, cells
other cancers and grown
normalintissues,
culture
are not readily
including heart,distinguished fromtissues.
kidney, and liver one another just
By the by looking;
early 1960s, a usually biochemical
central collection in
tests are needed
Washington, forand
D.C, identification. The cells
cultured human resultwere
is within a few cycles
an important tool of transfer,
in many a
areas
culture that started
of biological out as kidney cells or some other human cell could be taken
research.
over completely by rapidly
But in 1966, growing
geneticist HeLa
Stanley cells.
Gartler These
made cells then crowd
a devastating out the
discovery. He
original
analyzedcell line, just human
18 different as cancer
cellcells
linesdoand
in the body.
found that all had been contaminated
Henrietta
and taken over byLacks
HeLadied
cells.long ago
Over thefrom
nextthe
twocervical cancer that
years, scientists started the
confirmed HeLa
that 24
line,
of theyet
32these potent
cell lines in cells continue
the central to live on.
repository Their
were spread
actually throughout
HeLa human cell
cells. Researchers
cultures
who hadunderscores the unrelenting
spent years studying nature
what they of cancer,
thought were aheart
disease of uncontrolled
or kidney cells had in
growth and resource
reality been working consumption.
with a cervical cancer cell instead. Gartlers discovery meant
that hundreds of thousands of experiments performed in laboratories around the
world were invalid.

65
 Text 5
Because Cl transportConcepts,
across theChallenges,
membrane and
is closely linked to Na + transport,
Controversies
cells lining the respiratory
Cystic Fibrosis:airways
A Fatalcannot
Defectabsorb salt (NaCl)
in Membrane properly. As a
Transport
result, salt accumulates in the fluid lining the airways.
Cystic fibrosis
What has (CF),
puzzled
the most
researchers
common is fatal
how this
genetic
Cl disease
channelindefect
the United
and resultant
States,
salt accumulation
strikes 1 inlead
every
to2000
the excess
Caucasian
mucus
children.
problem.It Two
is characterized
recent discoveries
by the
production
have perhaps
of provided
abnormally
an thick,
answer,sticky
although
mucus.
these
Most
proposals
dramatically
remainaffected
to be proven
are
the respiratory
and research into
airways
other possible
and the pancreas.
mechanisms continues to be pursued. One
group of investigators
Respiratory problems found that the airway cells produce a natural antibiotic,
The presence
defensin, which
of normally
the thick, kills
stickymost
mucus
of the
in the
inhaled
respiratory
airborneairways
bacteria.
makes
It turns
it out
difficult
that defensin
to getcannot
adequate
function
air in properly
and out of
in the
salty
lungs.
environment.
Also, because
Bathed
bacteria
in the thrive
in the accumulated
excess salt associated
mucus,
with CF,
CF patients
the disabled
sufferantibiotic
from repeated
cannotrespiratory
rid the lungs of
infections.
inhaled bacteria.
They are
Thisespecially
leads to repeated
susceptible
infections.
to Pseudomonas
One of the
aeruginosa,
outcomes an
of the
opportunistic
bodys responsebacterium
to these infections
that is frequently
is excesspresent
mucus in
production.
the environment
In turn,but
this
usuallyserves
mucus causesasinfection
a breeding
onlyground
when for
somemore
underlying
bacterialproblem
growth. handicaps
The cycle the
bodys defense.
continues as the Gradually,
lung-clogging
the involved
mucus accumulation
lung tissue becomes
and frequency
scarredof(fibrotic),
lung
making thegrows
infections lungsever
harder
worse.
to inflate.
To makeThismatters
complication
wore, the
increases
excess the
mucus
work
id of
breathing beyond
especially thick and
thesticky,
extra work
making
required
it difficult
to move
for the
airnormal
throughciliary
the clogged
defense
airways.
mechanisms of the lung to sweep up the bacteria-laden mucus from the lungs
(see p.41 andCause
Underlying 444). The mucus is thick and sticky because it is under hydrated
During
(has toothe
little
lastwater),
decade,a problem
researchers
believes
foundtothat
be cystic
linkedfibrosis
to the defective
is causedsalt
by any
one of several different genetic defects that lead to production of a flawed
transport.
versionThe
of asecond
proteinnew
known
study
as found
cystic an
fibrosis
additional
transmembrane
complicating
conductance
factor in the CF
regulator
story. These
(CFTR).
researchers
CFTRdemonstrated
normally helps
thatform
CFTR
andappear
regulate
to the
serve
chloride
a dual (CL)
role as
achannels
Cl channel
in theand
plasma
as a membrane
membrane.receptor
With CFthat
thebinds
defective
with CFTR
P.aeruginosa
gets stuck
(and in
the endoplasmic
perhaps other bacteria).
reticulum/Golgi
CFTR subsequently
system, which
destroys
normally
the captured
manufactures
bacteria.
andIn
processes
the absence
this
of product
CFTR inand
theships
airway
it tocell
themembranes
plasma membrane
of CF patients,
(see p.26). That is,
in CF patientsisthe
P.aeruginosa notmutated
cleared version
from theofairways
CFTR isas only
usual.
partially
In a double
processed
onslaught,
and
never bacteria
these makes itwere
to theshown
cell surface.
to trigger
Thetheresultant
airway absence
cells to produce
of CFTRunusually
protein inlarge
the
plasma membranes Cl channels leads to membrane impermeability to Cl.

87
amounts of abnormal, thick, sticky mucus. This mucus promotes more bacterial
growth, as the vicious cycle continues.
Pancreatic Problems
Furthermore, in CF patients the pancreatic duct, which carries secretions from
the pancreas to the small intestine, becomes plugged with thick mucus. Because
the pancreas produces enzymes important in the digestion of food,
malnourishment eventually results. In addition, as the pancreatic digestive
secretions accumulate behind the blocked pancreatic duct, fluid-filled cysts
form in the pancreas, with the affected pancreatic tissue gradually degenerating
and becoming fibrotic. The name cystic fibrosis aptly describes long-term
changes that occur in the pancreas and lungs as the result of a single genetic
flaw in CFTR.
Treatment
Treatment consists of physical therapy to help clear the airways of the excess
mucus and antibiotic therapy to combat respiratory infections, plus special diets
and administration of supplemental pancreatic enzymes to maintain adequate
nutrition. Despite this supportive treatment, most CF victims do not survive
beyond their early 30s, with most dying from lung complications.
With the recent discovery of the genetic defect responsible for the
majority of CF cases, investigators are hopeful of developing a means to correct
or compensate for the defective gene. Another potential cure being studied is
development of drugs that induce the mutated CFTR to be finished off and
inserted in the plasma membrane. Furthermore, several promising new drug
therapy approaches, such as a mucus-thinning aerosol drugs that can be inhaled,
offer hope of reducing the number of lung infections and extending the life span
of CF victims until a cure can be found.

9
 Text 6
result of this stretch reflex causes the muscle to contract sufficiently to relieve
the stretch. A Closer Look at Exercise Physiology
Back Older
Swingspersons or thoseCrouches:
and Prejump with weakWhat
quadriceps
Do They(thigh)
Sharemuscles
in Common?
unknowingly take advantage of the muscle spindle by pushing on the center of
Proprioception,
the thighs when the
theysense
get up
of from
the bodys
a sitting
position
position.
in space,
Contraction
is critical
of the
to any
movement and
quadriceps muscle
is especially
extends the
important
knee joint,
in athletic
thus straightening
performance,
thewhether
leg. Theitact
be of
a
figure skater
pushing on the
performing
center of the
triple
thighs
jumps
when
on ice,
getting
a gymnast
up slightly
performing
stretchesa difficult
the
floor routine,
quadriceps muscle
or a football
in both quarterback
limbs, stimulating
throwing
the perfectly
muscle spindles.
to a spotThe
60 yards
resultant
downfield.
stretch reflex
Toaids
control
in contraction
skeletal muscle
of thecontraction
quadricepsto
muscles
achieveand
thehelps
desired
the person
movement,
assume a standing
the CNSposition.
must be continuously apprised of the results of its action,
throughInsensory
sports, feedback.
people use the muscle spindle to advantage all the time. To
jump high,
A as number
in basketball
of jump
receptors
ball, an athlete
providestartsproprioceptive
by crouching down.
input.
This Muscle
proprioceptors
action stretchesprovide
the quadriceps
feedbackmuscles
information
and increases
on muscle
thetension
firing rate
and of
length.
their
Joint proprioceptors
spindles, thus triggering
provide
the stretch
feedback
reflex
on joint
that reinforces
acceleration,
theangle,
quadriceps
and direction
of movement.
muscles contractile
Skin proprioceptors
response so that
inform
these the
extensor
CNS ofmuscles
weightof-bearing
the legspressure
gain
on the skin.power.
additional Proprioceptors
The samein
is the
trueinner
for crouch
ear, along
starts
with
in running
those inevents.
neck muscles,
The
provide information
backswing in tennis, about
golf, and
headbaseball
and necksimilarly
positionprovides
so that the
increased
CNS canmuscular
orient the
head correctly.
excitation through
For reflex
example,
activity
neckinitiated
reflexesby
facilitate
stretchedessential
muscletrunk
spindles.
and limb
movements during somersaults, and divers and tumblers use strong movements
of the head to maintain spins.
The most complex and probably one of the most important proprioceptors
is the muscle spindle (see p.282). Muscle spindles are found throughout a
muscle but tend to be concentrated in its center. Each spindle lies parallel to the
muscle fibers within the muscle. The spindle is sensitive to both the muscles
rate of change in length and the final length achieved. If a muscle is stretched,
each muscle spindle within the muscle is also stretched, and the afferent neuron
whose peripheral axon terminates on the muscle spindle is stimulated. The
afferent fiber passes into the spinal cord and synapses directly on the motor
neurons that supply the same muscle. Stimulation of the stretched muscle as a

10
11
 Text 7

reduced, but not to the A

same extent
Closer as renal
Look bloodPhysiology
at exercise flow, presumably because of
autoregulatory
Whenmechanisms (see
Protein in the p.351).
Urine DoesSome
Not investigators
Mean Kidneypropose
Diseasethat
decreased glomerular blood flow enhances diffusion of proteins into the tubular
Urinarybecause
lumen, loss of proteins
as the more
usually
slowly
signifies
flowingkidney
blooddisease
spends(nephritis).
more time However,
in the a
urinary protein
glomerulus, a greater
loss similar
proportion
to thatofofthe
nephritis
plasma often
protein
occurs
has time
following
to escape
exercise,
but the condition
through the glomerular
is harmless,
membrane.
transient,
Hormonal
and reversible.
changes that
The occur
term athletic
with exercise
pseudonephritis
may also affect glomerular
is used to describe
permeability.
this post
Forexercise
example,(after
reninexercise)
injectionproteinuria
is a well-
(protein in the
recognized wayurine).
to experimentally
Studies indicate
induce
thatproteinuria.
70% to 80%Plasma
of athletes
renninhave
activity
proteinuria
increase during
afterstrenuous
very strenuous
exercise
exercise.
and mayThis
contribute
conditiontooccurs
post exercise
in participants
in both noncontact
proteinuria. Researchers
and contact
also hypothesize
sports, so itthat
doesmaximal
not arisetubular
from physical
reabsorption
trauma
is
to the kidneys.
reached during In
severe
one study,
exercise,
subjects
whichwho
could
engaged
impairinprotein
maximal
reabsorption.
short-term
running excreted more protein than when they were bicycling, rowing, or
swimming at the same work intensity. The reason for this difference is
unknown.
Usually, only a very small fraction of the plasma proteins that enter the
glomerulus is filtered; those plasma proteins that are filtered are reabsorbed in
the tubules, so normally no plasma proteins appear in the urine. Two basic
mechanisms can cause proteinuria: (1) increased glomerular permeability with
no change in tubular reabsorption; or (2) impairment of tubular reabsorption.
Research has shown the proteinuria that occurs during mild to moderate
exercise results from changes in glomerular permeability, whereas the
proteinuria during short-term exhaustive exercise seems to be caused by both
increased glomerular permeability and tubular dysfunction.
This reversible kidney dysfunction is believed to result from circulatory
and hormonal changes that occur with exercise. Several studies have shown that
renal blood flow is reduced during exercise as the renal vessels are constricted
and blood is diverted to the exercising muscles. This reduction is positively
correlated with exercise intensity. With intense exercise, the renal blood flow
may be reduced to 20% of normal. As a result, glomerular blood flow is also

12
13
Text 8

A Closer Look at Exercise Physiology

Swan Dive or Belly Flop: Its a Matter of CNS Control

Sport skills must be learned. Much of the time, strong basic reflexes must be
overridden in order to perform the skill. Learning to dive into water, for
example, is very difficult initially. Strong head-righting reflexes controlled by
sensory organs in the neck and ears initiate a straightening of the neck and head
before the beginning diver enters the water, causing what is commonly known
as a belly flop. In a backward dive, the head-righting reflex causes the
beginner to land on his or her back or even in a sitting position. To perform any
motor skill that involves body inversions, somersaults, back flips, or other
abnormal postural movements, the person must learn to consciously inhibit
basic postural reflexes. This is accomplished by having the person concentrate
on specific body positions during the movement. For example, to perform a
somersault, the person must concentrate on keeping the chin tucked and
grabbing the knees. After the skill is performed repeatedly, new synaptic
patterns are formed in the CNS, and the new or conditioned response substitutes
for the natural reflex responses. Sport skills must be practiced until the
movement becomes automatic; then the athlete is free during competition to
think about strategy or the next move to be performed in a routine.

14
increasing
Text 9 the number of in-the-mouth
Concepts, electrodes.
Challenges, Even so, the perceived image
and Controversies
will still be crude because the Seeing
acuity afforded byTongue
with the this device can never come
close to matching that provided by the eyes small receptive fields.
Although
Although
each type
using
of sensory
the tongue
input
as is
a surrogate
received primarily
eye couldby
never
a distinct
providebrain
region responsible
anywhere near the same
for perception
vision as of
a normal
that modality,
eye, thethe
hope
regions
is thatofthis
the technique
brain
involved
will affordwith
people
perceptual
who areprocessing
blind a means
receive
to make
sensory
outsignals
doorways,
fromtoa see
variety
objects
of
sources.
as vagueThus,
shapes,
theand
visual
to track
cortex
motion.
receives
Even
sensory
this limited
input not
visual
onlyinput
fromwould
the eyes
but from
enable a sightless
the body person
surfacetoand
getears
around
as well.
easier
One
andgroup
improve
of scientists
the quality
is exploiting
of his or
in anlife.
her unusual
The devices
but exciting
developers
way this
plan
sharing
to shrink
of sensory
the sizeinput
of the
byunit
multiple
so thatregions
it will
of the
fit inconspicuously
brain. In this research,
in the users
blind
mouth
or sighted
and bebut
connected
blind folded
by a volunteers
wireless link
areto a
able to crudely
miniature camera
perceive
mountedshapes
on eyeglasses.
and features
Such
in space
a trimmed-down
by means ofunit
a tongue
would be
display unit.
practical to use
When
and this
cosmetically
device, which
acceptable.
consists of a grid of electrodes is
positioned on the tongue, it translates images detected by a camera into a pattern
of electrical signals that activate touch receptors on the tongue (see the
accompanying figure). The pattern of tingling on the tongue as a result of the
light-induced electrical signals corresponds with the image recorded by the
camera. With practice, the visual cortex interprets this alternate sensory input as
a visual image. As one of the investigators who developed this technique
claims, a person sees with the visual cortex, not with the eyes. Any means of
sending signals to the visual cortex can be perceived as a visual image. For
example, one blind participant in the study saw the flickering of a candle flame
for the first time by means of this tongue device.
The tongue is a better choice than the skin for receiving this light-turned-
tactile input because the saliva is an electrically conducive fluid that readily
conducts the current generated in the device by the visual input. Further-more,
the tongue is densely populated with tactile receptors, opening up the possibility
that the tongue can provide higher acuity of visual input than the skin could.
This feature will be important if such a device is ever used to help the visually
impaired. The researchers goal is to improve the resolution of the device by

15
16
suicide
Text 10in response to the chain of reactions unleashed by the toxic release of

glutamate from the initial site ofChallenges,

Concepts, O2 deprivation.
and Controversies
Until the last decade, physicians
Strokes: could
A Deadly do nothing
Domino Effectto halt the inevitable
neuronal loss following a stroke, leaving patients with an unpredictable mix of
The most
neural deficits.
common Treatment
cause of
was
brain
limited
damage
to rehabilitative
is a cerebrovascular
therapy accident
after the (CVA
damage
or stroke).
was alreadyWhen
complete.
a brain
In(cerebral)
recent years,
blood
armed
vessel
with
is blocked
new knowledge
by a clotabout
or ruptures,
the
the brain tissue
underlying factors
supplied
in stroke-related
by that vessel
neuronal
loses its
death,
vitalthe
O 2 medical
and glucose
community
supply. The
has
resultseeking
been is damage
ways
andtousually
halt thedeath
cell-killing
of the deprived
domino effect.
tissue.The
Newgoal,
findings
of course,
show is
thatlimit
to neural
the damage
extent of(and
neuronal
the subsequent
damage and
lossthus
of neural
minimize
function)
or evenextends
preventwell
beyond symptoms
clinical the blood-deprived
such as paralysis.
area as a result
In the of
early
a neurotoxic
1990s, doctors
effectstarted
that leads to
the death of additional
administering clot-dissolving
nearbydrugs
cells. within
Whereasthethe
first
initial
threeblood-deprived
hours after the cells
onsetdie
of
abystroke
necrosis
to restore
(unintentional
blood flow
cellthrough
death), the
blocked
doomed
cerebral
neighbors
vessels.
undergo
Clot busters
apoptosis
(deliberate
were the first
celldrugs
suicide;
usedsee
to treat
p. 120).
strokes,
The initial
but they
O2-starved
are only cells
the beginning
release of new
excessive
stroke therapies.
amountsOther
of glutamate,
methods are
a common
currentlyexcitatory
under investigation
neurotransmitter.
to prevent
Glutamate
adjacent nerve
or other
cellsneurotransmitters
from succumbingare
to the
normally
neurotoxic
released
release
in small
of glutamate.
amounts
from neurons
These includeas
blocking
a meansthe
ofNMDA
chemical
receptors
communication
that initiate
between
the death-wielding
brain cells. The
excitatory
chain of events
overdose
in response
of glutamate
to glutamate,
from thehalting
damagedthe brain
apoptosis
cells pathway
binds with
thatand
results in self
overexcites execution, neurons.
surrounding and blocking the gap junctions
Specifically, glutamatethat permit
binds withthe Ca 2+
excitatory
receptors
death known as
messenger NMDAtoreceptors,
to spread whichThese
adjacent cells. function as Ca
tactics 2+ channels.
hold As a
much promise
result
for treating
of toxic
strokes,
activation
whichofare
these
thereceptor-channels,
most prevalent cause
theyofremain
adult disability
open for too
and
long,
the permitting
third leading too much
cause Ca2+ to
of death in rush into theStates.
the United affected neighboring
However, to dateneurons.
no new
This elevated intracellular
neuroprotective drugs haveCa 2+ triggers
been thesedocells
found that not to self-destruct.
cause During
serious side this
effects.
process, free radicals are produced. These highly reactive, electron-deficient
particles cause further cell damage by snatching electrons from other molecules.
Adding to the injury, researchers speculate that the Ca 2+ apoptotic signal may

spread from the dying cells to abutting healthy cells through gap junctions, cell-
to-cell conduits that allow Ca2+ and other small ions to diffuse freely between

cells. This action kills even more neuronal victims. Thus, the majority of
neurons that die following a stroke are originally unharmed cells that commit

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