acute stroke-a stage of
stroke starting at the onset of symptoms and last
for a few hours thereafter.
agnosia-a cognitive
disability characterized by ignorance of or
inability to acknowledge one side of the body or one
side of the visual field.
aneurysm -a weak or
thin spot on an artery wall that has stretched or
ballooned out from the wall and filled with blood,
or damage to an artery leading to pooling of blood
between the layers of the blood vessel walls.
anoxia-a state of
almost no oxygen delivery to a cell, resulting in
low energy production and possible death of the cell;
see hypoxia.
anticoagulants-a drug
therapy used to prevent the formation of blood clots
that can become lodged in cerebral arteries and
cause strokes.
antiplatelet agents-a
type of anticoagulant drug therapy that prevents the
formation of blood clots by preventing the
accumulation of platelets that form the basis of
blood clots; some common antiplatelets include
aspirin and ticlopidine; see anticoagulants.
antithrombotics-a type
of anticoagulant drug therapy that prevents the
formation of blood clots by inhibiting the
coagulating actions of the blood protein thrombin;
some common antithrombotics include warfarin and
heparin; see anticoagulants.
aphasia-the inability
to understand or create speech, writing, or language
in general due to damage to the speech centers of
the brain.
apoplexy-a historical,
but obsolete term for a cerebral stroke, most often
intracerebral hemorrhage, that was applied to any
condition that involved disorientation and/or
paralysis.
apoptosis- a form of
cell death involving shrinking of the cell and
eventual disposal of the internal elements of the
cell by the body's immune system. Apoptosis is an
active, non-toxic form of cell suicide that does not
induce an inflammatory response. It is often called
programmed cell death because it is triggered by a
genetic signal, involves specific cell mechanisms,
and is irreversible once initiated.
apraxia-a movement
disorder characterized by the inability to perform
skilled or purposeful voluntary movements, generally
caused by damage to the areas of the brain
responsible for voluntary movement.
arteriography-an X-ray
of the carotid artery taken when a special dye is
injected into the artery.
arteriovenous malformation (AVM)-a
congenital disorder characterized by a complex
tangled web of arteries and veins.
atherosclerosis-a blood
vessel disease characterized by deposits of lipid
material on the inside of the walls of large to
medium-sized arteries which make the artery walls
thick, hard, brittle, and prone to breaking.
atrial fibrillation-irregular
beating of the left atrium, or left upper chamber,
of the heart.
blood-brain barrier-an
elaborate network of supportive brain cells, called
glia, that surrounds blood vessels and protects
neurons from the toxic effects of direct exposure to
blood.
carotid artery-an
artery, located on either side of the neck, that
supplies the brain with blood.
carotid endarterectomy-surgery
used to remove fatty deposits from the carotid
arteries.
central stroke pain (central pain
syndrome)-pain caused by damage to an
area in the thalamus. The pain is a mixture of
sensations, including heat and cold, burning,
tingling, numbness, and sharp stabbing and
underlying aching pain.
cerebral blood flow (CBF)-the
flow of blood through the arteries that lead to the
brain, called the cerebrovascular system.
cerebrospinal fluid (CSF)-clear fluid
that bathes the brain and spinal cord.
cerebrovascular disease-a
reduction in the supply of blood to the brain either
by narrowing of the arteries through the buildup of
plaque on the inside walls of the arteries, called
stenosis, or through blockage of an artery due to a
blood clot.
cholesterol-a waxy
substance, produced naturally by the liver and also
found in foods, that circulates in the blood and
helps maintain tissues and cell membranes. Excess
cholesterol in the body can contribute to
atherosclerosis and high blood pressure.
"clipping"-surgical
procedure for treatment of brain aneurysms,
involving clamping an aneurysm from a blood vessel,
surgically removing this ballooned part of the blood
vessel, and closing the opening in the artery wall.
computed tomography (CT) scan-a
series of cross-sectional X-rays of the brain and
head; also called computerized axial tomography or
CAT scan.
Coumadin®-a
commonly used anticoagulant, also known as warfarin.
cytokines-small,
hormone-like proteins released by leukocytes,
endothelial cells, and other cells to promote an
inflammatory immune response to an injury.
cytotoxic edema-a state
of cell compromise involving influx of fluids and
toxic chemicals into a cell causing subsequent
swelling of the cell.
detachable coil-a
platinum coil that is inserted into an artery in the
thigh and strung through the arteries to the site of
an aneurysm. The coil is released into the aneurysm
creating an immune response from the body. The body
produces a blood clot inside the aneurysm,
strengthening the artery walls and reducing the risk
of rupture.
duplex Doppler ultrasound-a
diagnostic imaging technique in which an image of an
artery can be formed by bouncing sound waves off the
moving blood in the artery and measuring the
frequency changes of the echoes.
dysarthria-a disorder
characterized by slurred speech due to weakness or
incoordination of the muscles involved in speaking.
dysphagia-trouble
swallowing.
edema-the swelling of a
cell that results from the influx of large amounts
of water or fluid into the cell.
embolic stroke-a stroke
caused by an embolus.
embolus-a free-roaming
clot that usually forms in the heart.
endothelial wall-a flat
layer of cells that make up the innermost lining of
a blood vessel.
excitatory amino acids-a
subset of neurotransmitters; proteins released by
one neuron into the space between two neurons to
promote an excitatory state in the other neuron.
extracranial/intracranial (EC/IC)
bypass-a type of surgery that restores
blood flow to a blood-deprived area of brain tissue
by rerouting a healthy artery in the scalp to the
area of brain tissue affected by a blocked artery.
functional magnetic resonance imaging
(fMRI)-a type of imaging that measures
increases in blood flow within the brain.
glia-also called
neuroglia; supportive cells of the nervous system
that make up the blood-brain barrier, provide
nutrients and oxygen to the vital neurons, and
protect the neurons from infection, toxicity, and
trauma. Some examples of glia are oligodendroglia,
astrocytes, and microglia.
glutamate-also known as
glutamic acid, an amino acid that acts as an
excitatory neurotransmitter in the brain.
hemiparesis-weakness on
one side of the body.
hemiplegia-complete
paralysis on one side of the body.
hemorrhagic stroke-sudden bleeding
into or around the brain.
heparin-a type of
anticoagulant.
high-density lipoprotein (HDL)-also
known as the good cholesterol; a compound consisting
of a lipid and a protein that carries a small
percentage of the total cholesterol in the blood and
deposits it in the liver.
homeostasis-a state of
equilibrium or balance among various fluids and
chemicals in a cell, in tissues, or in the body as a
whole.
hypertension (high blood pressure)-characterized
by persistently high arterial blood pressure defined
as a measurement greater than or equal to 140 mm/Hg
systolic pressure over 90 mm/Hg diastolic pressure.
hypoxia-a state of
decreased oxygen delivery to a cell so that the
oxygen falls below normal levels; see
anoxia.
incidence-the extent or
frequency of an occurrence; the number of specific
new events in a given period of time.
infarct-an area of
tissue that is dead or dying because of a loss of
blood supply.
infarction-a sudden
loss of blood supply to tissue, causing the
formation of an infarct.
interleukins-a group of
cytokine-related proteins secreted by leukocytes and
involved in the inflammatory immune response of the
ischemic cascade.
intracerebral hemorrhage-occurs
when a vessel within the brain leaks blood into the
brain.
ischemia-a loss of
blood flow to tissue, caused by an obstruction of
the blood vessel, usually in the form of plaque
stenosis or a blood clot.
ischemic cascade-a
series of events lasting for several hours to
several days following initial ischemia that results
in extensive cell death and tissue damage beyond the
area of tissue originally affected by the initial
lack of blood flow.
ischemic penumbra-areas
of damaged, but still living, brain cells arranged
in a patchwork pattern around areas of dead brain
cells.
ischemic stroke-ischemia
in the tissues of the brain.
lacunar infarction-occlusion
of a small artery in the brain resulting in a small
area of dead brain tissue, called a lacunar infarct;
often caused by stenosis of the small arteries,
called small vessel disease.
large vessel disease-stenosis
in large arteries of the cerebrovascular system.
leukocytes-blood
proteins involved in the inflammatory immune
response of the ischemic cascade.
lipoprotein-small
globules of cholesterol covered by a layer of
protein; produced by the liver.
low-density lipoprotein (LDL)-also
known as the bad cholesterol; a compound consisting
of a lipid and a protein that carries the majority
of the total cholesterol in the blood and deposits
the excess along the inside of arterial walls.
magnetic resonance angiography (MRA)-an
imaging technique involving injection of a contrast
dye into a blood vessel and using magnetic resonance
techniques to create an image of the flowing blood
through the vessel; often used to detect stenosis of
the brain arteries inside the skull.
magnetic resonance imaging (MRI) scan-a
type of imaging involving the use of magnetic fields
to detect subtle changes in the water content of
tissues.
mitochondria-the energy
producing organelles of the cell.
mitral annular calcification-a
disease of the mitral valve of the heart.
mitral valve stenosis-a
disease of the mitral heart valve involving the
buildup of plaque-like material on and around the
valve.
necrosis-a form of cell
death resulting from anoxia, trauma, or any other
form of irreversible damage to the cell; involves
the release of toxic cellular material into the
intercellular space, poisoning surrounding cells.
neuron-the main
functional cell of the brain and nervous system,
consisting of a cell body, an axon, and dendrites.
neuroprotective agents-medications
that protect the brain from secondary injury caused
by stroke.
oxygen-free radicals-toxic
chemicals released during the process of cellular
respiration and released in excessive amounts during
necrosis of a cell; involved in secondary cell death
associated with the ischemic cascade.
plaque-fatty
cholesterol deposits found along the inside of
artery walls that lead to atherosclerosis and
stenosis of the arteries.
plasticity-the ability
to be formed or molded; in reference to the brain,
the ability to adapt to deficits and injury.
platelets-structures
found in blood that are known primarily for their
role in blood coagulation.
prevalence-the number
of cases of a disease in a population at any given
point in time.
recombinant tissue plasminogen
activator (rt-PA)-a genetically
engineered form of t-PA, a thrombolytic,
anti-clotting substance made naturally by the body.
small vessel disease-a
cerebrovascular disease defined by stenosis in small
arteries of the brain.
stenosis-narrowing of
an artery due to the buildup of plaque on the inside
wall of the artery.
stroke belt-an area of
the southeastern United States with the highest
stroke mortality rate in the country.
stroke buckle-three
southeastern states, North Carolina, South Carolina,
and Georgia, that have an extremely high stroke
mortality rate.
subarachnoid hemorrhage-bleeding
within the meninges, or outer membranes, of the
brain into the clear fluid that surrounds the brain.
thrombolytics-drugs
used to treat an ongoing, acute ischemic stroke by
dissolving the blood clot causing the stroke and
thereby restoring blood flow through the artery.
thrombosis-the
formation of a blood clot in one of the cerebral
arteries of the head or neck that stays attached to
the artery wall until it grows large enough to block
blood flow.
thrombotic stroke-a
stroke caused by thrombosis.
tissue necrosis factors-chemicals
released by leukocytes and other cells that cause
secondary cell death during the inflammatory immune
response associated with the ischemic cascade.
total serum cholesterol-a
combined measurement of a person's high-density
lipoprotein (HDL) and low-density lipoprotein (LDL).
t-PA-see recombinant
tissue plasminogen activator.
transcranial magnetic stimulation
(TMS)-a small magnetic current
delivered to an area of the brain to promote
plasticity and healing.
transient ischemic attack (TIA)-a
short-lived stroke that lasts from a few minutes up
to 24 hours; often called a mini-stroke.
vasodilators-medications
that increase blood flow to the brain by expanding
or dilating blood vessels.
vasospasm-a dangerous
side effect of subarachnoid hemorrhage in which the
blood vessels in the subarachnoid space constrict
erratically, cutting off blood flow.
vertebral artery-an
artery on either side of the neck; see
carotid artery.
warfarin-a commonly
used anticoagulant, also known as Coumadin®.
The Ischemic Cascade
The brain is the most complex
organ in the human body. It contains hundreds of
billions of cells that interconnect to form a
complex network of communication. The brain has
several different types of cells, the most important
of which are neurons. The organization of
neurons in the brain and the communication that
occurs among them lead to thought, memory, cognition,
and awareness. Other types of brain cells are
generally called glia (from the Greek word
meaning "glue"). These supportive cells of the
nervous system provide scaffolding and support for
the vital neurons, protecting them from infection,
toxins, and trauma. Glia make up the blood-brain
barrier between blood vessels and the substance of
the brain.
Stroke is the sudden onset of paralysis caused by
injury to brain cells from disruption in blood flow.
The injury caused by a blocked blood vessel can
occur within several minutes and progress for hours
as the result of a chain of chemical reactions that
is set off after the start of stroke symptoms.
Physicians and researchers often call this chain of
chemical reactions that lead to the permanent brain
injury of stroke the ischemic cascade.
Primary Cell Death
In the first stage of the ischemic cascade, blood
flow is cut off from a part of the brain (ischemia).
This leads to a lack of oxygen (anoxia) and lack of
nutrients in the cells of this core area. When the
lack of oxygen becomes extreme, the mitochondria,
the energy-producing structures within the cell, can
no longer produce enough energy to keep the cell
functioning. The mitochondria break down, releasing
toxic chemicals called oxygen-free radicals
into the cytoplasm of the cell. These toxins poison
the cell from the inside-out, causing destruction of
other cell structures, including the nucleus.
The lack of energy in the cell causes the gated
channels of the cell membrane that normally maintain
homeostasis to open and allow toxic amounts
of calcium, sodium, and potassium ions to flow into
the cell. At the same time, the injured ischemic
cell releases excitatory amino acids, such as
glutamate, into the space between neurons, leading
to overexcitation and injury to nearby cells. With
the loss of homeostasis, water rushes into the cell
making it swell (called cytotoxic edema) until the
cell membrane bursts under the internal pressure. At
this point the nerve cell is essentially permanently
injured and for all purposes dead (necrosis
and infarction). After a stroke starts, the
first cells that are going to die may die within 4
to 5 minutes. The response to the treatment that
restores blood flow as late as 2 hours after stroke
onset would suggest that, in most cases, the process
is not over for at least 2 to 3 hours. After that,
with rare exceptions, most of the injury that has
occurred is essentially permanent.
Secondary Cell Death
Due to exposure to excessive amounts of glutamate,
nitric oxide, free radicals, and excitatory amino
acids released into the intercellular space by
necrotic cells, nearby cells have a more difficult
time surviving. They are receiving just enough
oxygen from cerebral blood flow (CBF) to stay
alive. A compromised cell can survive for several
hours in a low-energy state. If blood flow is
restored within this narrow window of opportunity,
at present thought to be about 2 hours, then some of
these cells can be salvaged and become functional
again. Researchers funded by the NINDS have learned
that restoring blood flow to these cells can be
achieved by administrating the clot-dissolving
thrombolytic agent t-PA within 3 hours of the start
of the stroke.
Inflammation and the Immune Response
While anoxic and necrotic brain cells are doing
damage to still viable brain tissue the immune
system of the body is injuring the brain through an
inflammatory reaction mediated by the vascular
system. Damage to the blood vessel at the site of a
blood clot or hemorrhage attracts inflammatory blood
elements to that site. Among the first blood
elements to arrive are leukocytes, white
blood cells that are covered with immune system
proteins that attach to the blood vessel wall at the
site of the injury. After they attach, the
leukocytes penetrate the endothelial wall, move
through the blood-brain barrier, and invade the
substance of the brain causing further injury and
brain cell death. Leukocytes called monocytes and
macrophages release inflammatory chemicals (cytokines,
interleukins, and tissue necrosis factors)
at the site of the injury. These chemicals make it
harder for the body to naturally dissolve a clot
that has caused a stroke by inactivating anti-clotting
factors and inhibiting the release of natural tissue
plasminogen activator. NINDS researchers are
currently working to create interventional therapies
that will inhibit the effects of cytokines and other
chemicals in the inflammatory process during stroke.
These brain cells that survive the loss of blood
flow (ischemia) but are not able to function make up
the ischemic penumbra. These areas of still-viable
brain cells exist in a patchwork pattern within and
around the area of dead brain tissue (also called an
infarct).
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