Brain ischemia, also known as
cerebral ischemia, is a condition in which there is insufficient blood flow to the
brainThe brain is the center of the nervous system in all vertebrate, and most invertebrate, animals. Some primitive animals such as jellyfish and starfish have a decentralized nervous system without a brain, while sponges lack any nervous system at all...
to meet metabolic demand. This leads to poor oxygen supply or
cerebral hypoxiaCerebral hypoxia refers to deprivation of oxygen supply to brain tissue. Mild or moderate cerebral hypoxia is sometimes known as diffuse cerebral hypoxia. It can cause confusion and fainting, but its effects are reversible. Total deprivation of oxygen to the brain is called cerebral anoxia...
and thus to the death of brain tissue or
cerebral infarctionA cerebral infarction is the ischemic kind of stroke due to a disturbance in the blood vessels supplying blood to the brain. It can be atherothrombotic or embolic. From stroke caused by cerebral infarction two other kinds of stroke should be distinguished: cerebral hemorrhage and subarachnoid...
/ ischemic
strokeA stroke is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by thrombosis or embolism or due to a hemorrhage...
. It is a sub-type of stroke along with
subarachnoid hemorrhageA subarachnoid hemorrhage is bleeding into the subarachnoid space—the area between the arachnoid membrane and the pia mater surrounding the brain...
and intracerebral hemorrhage.
Ischemia leads to alterations in brain metabolism, reduction in metabolic rates, and energy crisis.
There are two types of ischemia: focal ischemia, which is confined to a specific region of the brain; and global ischemia, which encompasses wide areas of brain tissue.
The main symptoms involve impairments in
visionVisual perception is the ability to interpret information and surroundings from visible light reaching the eye. The resulting perception is also known as eyesight, sight or vision...
, body movement, and speaking. The causes of brain ischemia vary from sickle cell anemia to congenital heart defects. Symptoms of brain ischemia can include unconsciousness, blindness, problems with coordination, and weakness in the body. Other effects that may result from brain ischemia are
strokeA stroke is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by thrombosis or embolism or due to a hemorrhage...
, cardiorespiratory arrest, and irreversible brain damage.
Background
An interruption of blood flow to the brain for more than ten seconds results in the loss of consciousness and leads to brain ischemia, consequently resulting in irreversible brain damage. The brain is one of the most important organs in the body, regulating all bodily functions and activities. The five essential parts of the brain are the cerebrum,
cerebellumThe cerebellum is a region of the brain that plays an important role in the integration of sensory perception, coordination and motor control...
,
brain stemThe brainstem is the lower part of the brain, adjoining and structurally continuous with the spinal cord. The brain stem provides the main motor and sensory innervation to the face and neck via the cranial nerves...
,
pituitary glandThe pituitary gland, or hypophysis, is an endocrine gland about the size of a pea and weighing 0.5 g . It is a protrusion off the bottom of the hypothalamus at the base of the brain, and rests in a small, bony cavity covered by a dural fold...
, and
hypothalamusThe hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions of the hypothalamus is to link the nervous system to the endocrine system via the pituitary gland ....
. Generally, the proper functioning of all regions of the brain is imperative to normal activity.
History
It was believed for many years that multiple incidents of brain ischemia would eventually lead to irreversible damage . In 1974, Hossmann and
ZimmermanZimmerman derives from the German last name Zimmermann which means carpenter. Within the United States, it is ranked as the 441st-most common surname....
challenged this assumption using animal studies and demonstrated that ischemia induced in mammalian brains for up to an hour can be at least partially recovered. Accordingly, this discovery raised the possibility of intervening after brain ischemia before the damage becomes irreversible.
Classification
The broad term, "
strokeA stroke is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by thrombosis or embolism or due to a hemorrhage...
" can be divided into three categories: brain ischemia,
subarachnoid hemorrhageA subarachnoid hemorrhage is bleeding into the subarachnoid space—the area between the arachnoid membrane and the pia mater surrounding the brain...
and intracerebral hemorrhage. Brain ischemia can be further subdivided, by cause, into
thromboticThrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot, because the first step in repairing it is to prevent loss of blood...
, embolic, and hypoperfusion. Thrombotic and embolic are generally focal or multifocal in nature while hypoperfusion affects the brain globally.
Focal brain ischemia
Focal brain ischemia occurs when a blood clot has occluded a cerebral vessel. Focal brain ischemia reduces blood flow to a specific brain region, increasing the risk of cell death to that particular area. It can be either caused by
thrombosisThrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot, because the first step in repairing it is to prevent loss of blood...
or embolism.
Global brain ischemia
Global brain ischemia occurs when blood flow to the brain is halted or drastically reduced. This is commonly caused by
cardiac arrestA cardiac arrest, also known as cardiopulmonary arrest or circulatory arrest, is the abrupt cessation of normal circulation of the blood due to failure of the heart to contract effectively during systole....
. If sufficient Circulatory system|circulation is restored within a short period of time, symptoms may be transient. However, if a significant amount of time passes before restoration, brain damage may be permanent. While reperfusion may be essential to protecting as much brain tissue as possible, it may also lead to
reperfusion injuryReperfusion injury refers to damage to tissue caused when blood supply returns to the tissue after a period of ischemia. The absence of oxygen and nutrients from blood creates a condition in which the restoration of circulation results in inflammation and oxidative damage through the induction of...
. Reperfusion injury is classified as the damage that ensues after restoration of blood supply to ischemic tissue.
Symptoms
The symptoms of brain ischemia reflect the anatomical region undergoing blood and oxygen deprivation. Ischemia within the arteries branching from the
internal carotid arteryIn human anatomy, the internal carotid artery is a major artery of the head and neck that helps supply blood to the brain.-Classification:Terminologia Anatomica currently breaks the artery into four parts: "cervical", "petrous", "cavernous", and "cerebral"...
may result in symptoms such as blindness in one eye, weakness in one arm or leg, or weakness in one entire side of the body. Ischemia within the arteries branching from the
vertebral arteriesThe vertebral arteries are branches of the subclavian arteries.The two vertebral arteries and the basilar artery are sometimes together called the vertebrobasilar system, which supplies blood to the posterior part of circle of Willis and anastomoses with blood supplied to the anterior part of the...
in the back of the brain may result in symptoms such as
dizzinessDizziness refers to an impairment in spatial perception and stability. It is considered imprecise. It can be used to mean vertigo, presyncope, disequilibrium, or for a non-specific feeling such as giddiness or foolishness....
,
vertigoVertigo is a specific type of dizziness, a major symptom of a balance disorder. It is the sensation of spinning or swaying while the body is actually stationary with respect to the surroundings.The effects of vertigo may be slight...
,
double visionDiplopia, commonly known as double vision, is the simultaneous perception of two images of a single object. These images may be displaced horizontally, vertically, or diagonally Diplopia, commonly known as double vision, is the simultaneous perception of two images of a single object. These images...
, or weakness on both sides of the body . Other symptoms include, difficulty speaking, slurred speech, and the loss of coordination. The symptoms of brain ischemia range from mild to severe. Further, symptoms can last from a few seconds to a few minutes or extended periods of time. If the brain becomes damaged irreversibly and
infarctionIn medicine, an infarction is the process of tissue death caused by blockage of the tissue's blood supply. The supplying artery may be blocked by an obstruction , may be mechanically compressed , ruptured by trauma , or vasoconstricted In medicine, an infarction is the process of tissue death...
occurs, the symptoms may be permanent.
Similar to
cerebral hypoxiaCerebral hypoxia refers to deprivation of oxygen supply to brain tissue. Mild or moderate cerebral hypoxia is sometimes known as diffuse cerebral hypoxia. It can cause confusion and fainting, but its effects are reversible. Total deprivation of oxygen to the brain is called cerebral anoxia...
, severe or prolonged brain ischemia will result in
unconsciousnessUnconsciousness, more appropriately referred to as loss of consciousness or lack of consciousness, is a dramatic alteration of mental state that involves complete or near-complete lack of responsiveness to people and other environmental stimuli. Being in a comatose state or coma is an illustration...
,
brain damageBrain damage, or acquired brain injury, is the destruction or degeneration of brain cells.-Causes:Brain damage may occur due to a wide range of conditions, illnesses, injuries, and as a result of iatrogenesis...
or
deathDeath is the termination of the biological functions that define a living organism. It refers to both a particular event and to the condition that results thereby. The true nature of the latter has for millennia been a central concern of the world's religious traditions and of philosophical...
, mediated by the
ischemic cascadeThe ischemic cascade is a series of biochemical reactions that take place in the brain and other aerobic tissues after seconds to minutes of ischemia . This is typically secondary to stroke, injury, or cardiac arrest due to heart attack. Most ischemic neurons that die do so due to the activation...
.
Multiple cerebral ischemic events may lead to
subcortical ischemic depressionSubcortical ischemic depression, also known as vascular depression is a medical condition most commonly seen in elderly depressed patients. Late onset depression is increasingly seen as a distinct variety of depression, and is commonly detected with an MRI...
, also known as vascular depression. This condition is most commonly seen in elderly depressed patients. Late onset depression is increasingly seen as a distinct sub-type of depression, and can be detected with an MRI.
Causes
Brain ischemia has been linked to a variety of diseases or abnormalities. Individuals with sickle cell anemia, compressed blood vessels,
ventricular tachycardiaVentricular tachycardia is a tachycardia, or fast heart rhythm, that originates in one of the ventricles of the heart...
, plaque buildup in the arteries, blood clots, extremely low blood pressure as a result of heart attack, and congenital heart defects have a higher predisposition to brain ischemia in comparison their healthy counterparts.
Sickle cell anemia may cause brain ischemia associated with the irregularly shaped blood cells. Sickle shaped blood cells clot more easily than normal blood cells, impeding blood flow to the brain.
Compression of blood vessels may also lead to brain ischemia, by blocking the arteries that carry oxygen to the brain. Tumors are one cause of blood vessel compression.
Ventricular tachycardia represents a series of irregular heartbeats that may cause the heart to completely shut down resulting in cessation of oxygen flow. Further, irregular heartbeats may result in formation of blood clots, thus leading to oxygen deprivation to all organs.
Blockage of arteries due to plaque buildup may also result in ischemia. Even a small amount of plaque build up can result in the narrowing of passageways, causing that area to become more prone to blood clots. Large blood clots can also cause ischemia by blocking blood flow.
A heart attack can also cause brain ischemia due to the correlation that exists between heart attack and low blood pressure. Extremely low blood pressure usually represents the inadequate oxygenation of tissues. Untreated heart attacks may slow blood flow enough that blood may start to clot and prevent the flow of blood to the brain or other major organs. Extremely low blood pressure can also result from drug overdose and reactions to drugs. Therefore, brain ischemia can result from events other than heart attacks.
Congenital heart defects may also cause brain ischemia due to the lack of appropriate artery formation and connection. People with congenital heart defects may also be prone to blood clots.
Other pathological events that may result in brain ischemia include, cardiorespiratory arrest,
strokeA stroke is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by thrombosis or embolism or due to a hemorrhage...
, and severe irreversible brain damage.
Recently, Moyamoya disease has also been identified as a potential cause for brain ischemia. Moyamoya disease is an extremely rare cerebrovascular condition that limits blood
circulation- [Headline text]--75.137.171.242 01:21, 21 October 2009 :bThe circulatory system is an organ system that passes nutrients , gases, hormones, blood cells, nitrogen waste products, etc. to and from cells in the body to help fight diseases and help stabilize body temperature and pHb to maintain...
to the brain, consequently leading to oxygen deprivation.
Pathophysiology
During brain ischemia, the brain cannot perform aerobic metabolism due to the loss of
oxygenOxygen Oxygen Oxygen (acid, literally "sharp", from the taste of acids) and -γενής (-genēs) (producer, literally begetter) is the element with atomic number 8 and represented by the symbol O...
and
substrateIn biochemistry, a substrate is a molecule upon which an enzyme acts. Enzymes catalyze chemical reactions involving the substrate. In the case of a single substrate, the substrate binds with the enzyme active site, and an enzyme-substrate complex is formed. The substrate is transformed into one or...
. The brain is not able to switch to anaerobic metabolism because it does not have any long term energy stored. Thus, the levels of
adenosine triphosphateAdenosine-5'-triphosphate is a multifunctional nucleotide that plays an important role in cell biology as a coenzyme, that is, the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
(ATP) drop rapidly. In the absence of biochemical energy, cells begin to lose the ability to maintain electrochemical gradients. Consequently, there is a massive influx of
calciumCalcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft grey alkaline earth metal, and is the fifth most abundant element by mass in the Earth's crust...
into the
cytosolThe cytosol or intracellular fluid is the liquid found inside cells. In eukaryotes this liquid is separated by cell membranes from the contents of the organelles suspended in the cytosol, such as the mitochondrial matrix inside the mitochondrion...
, a massive release of glutamate from synaptic vesicles,
lipolysisLipolysis is the breakdown of fat stored in fat cells. During this process, free fatty acids are released into the bloodstream and circulate throughout the body. Ketones are produced, and are found in large quantities in ketosis...
,
calpainCalpains are a family of calcium-dependent, non-lysosomal cysteine proteases expressed ubiquitously in mammals and many other organisms. Calpains constitute the C2 family of protease clan CA in the MEROPS database. The calpain proteolytic system includes the calpain proteases, the small...
activation, and the arrest of
protein synthesis. Additinoally, removal of metabolic wastes is slowed. The interruption of blood flow to the brain for ten seconds results in the immediate loss of consciousness. The interruption of blood flow for twenty seconds results in the stopping of electrical activity.
Treatment
The outcome of brain ischemia is influenced by the quality of subsequent supportive care. Systemic blood pressure (or slightly above) should be maintained so that cerebral blood flow is restored. Also, hypoxaemia and
hypercapniaHypercapnia or hypercapnea , also known as hypercarbia, is a condition where there is too much carbon dioxide in the blood...
should be avoided. Seizures can induce more damage; accordingly, anticonvulsants should be prescribed and should a seizure occur, aggressive treatment should be undertaken. Hyperglycaemia should also be avoided during brain ischemia.
Management
When someone presents with an ischemic event, treatment of the underlying cause is critical for prevention of further episodes.
Anticoagulation with
warfarinWarfarin is an anticoagulant. It was initially marketed as a pesticide against rats and mice and is still popular for this purpose, although more potent poisons such as brodifacoum have since been developed...
or
heparinHeparin, a highly-sulfated glycosaminoglycan, is widely used as an injectable anticoagulant, and has the highest negative charge density of any known biological molecule. It can also be used to form an inner anticoagulant surface on various experimental and medical devices such as test tubes and...
may be used if the patient has
atrial fibrillationAtrial fibrillation is the most common cardiac arrhythmia and involves the two upper chambers of the heart. Its name comes from the fibrillating of the heart muscles of the atria, instead of a coordinated contraction...
.
Operative procedures such as
carotid endarterectomyCarotid endarterectomy is a surgical procedure used to prevent stroke, by correcting stenosis in the carotid artery. Endarterectomy is the removal of material on the inside of an artery....
may be performed if the patient has a significant amount of plaque in the carotid arteries associated with the local ischemic events.
Research
A study published in the British Medical Journal established, from the results of animal studies, a correlation between the effects of brain ischemia and the type of ischemia involved.
Therapeutic hypothermiaTherapeutic hypothermia is a medical treatment that lowers a patient's body temperature in order to help reduce the risk of the ischemic injury to tissue following a period of insufficient blood flow. Periods of insufficient blood flow may be due to cardiac arrest or the occlusion of an artery by...
has been attempted to improve results post brain ischemia . This procedure was suggested to be beneficial based on its effects post cardiac arrest. Evidence supporting the use of therapeutic hypothermia after brain ischemia, however, is limited.
A closely related disease to brain ischemia is brain hypoxia. Brain hypoxia is the condition in which there is a decrease in the oxygen supply to the brain even in the presence of adequate
blood flowBlood flow is the flow of blood in the cardiovascular system.It can be calculated by dividing the vascular resistance into the pressure gradient.-Physics:...
. If hypoxia lasts for long periods of time,
comaIn medicine, a coma is a profound state of unconsciousness. A comatose person cannot be awakened, fails to respond normally to pain or light, does not have sleep-wake cycles, and does not take voluntary actions....
, seizures, and even
brain deathBrain death is a legal definition of death that refers to the irreversible end of all brain activity due to total necrosis of the cerebral neurons following loss of blood flow and oxygenation. It should not be confused with a persistent vegetative state...
may occur. Symptoms of brain hypoxia are similar to ischemia and include, inattentiveness, poor judgment,
memory lossMemory loss can have many causes:*Alzheimer's disease is an illness which can cause mild to severe memory loss.*Parkinson's disease is a genetic defect which may result in memory loss....
, and a decrease in
motor coordinationMotor coordination is a term used to refer to the coordination of movements, usually between different subsequent parts of the same movement or movements of several limbs or even several actors.Motor coordination arise from a complex coordination between:...
. Potential causes of brain hypoxia are
suffocationSuffocation is the process of being asphyxiated.It may also refer to:* Suffocation, death metal band.* "Suffocate", a song by the post-grunge band Finger Eleven from their 2000 album The Greyest of Blue Skies....
,
carbon monoxide poisoningCarbon monoxide poisoning occurs after enough inhalation of carbon monoxide . Carbon monoxide is a toxic gas, but, being colorless, odorless, tasteless, and non-irritating, it is very difficult for people to detect...
, severe
anemiaAnemia is a decrease in normal number of red blood cells or less than the normal quantity of hemoglobin in the blood...
, and use of drugs such as
cocaineCocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system and an appetite suppressant...
and other amphetamines. Other causes associated with brain hypoxia include
drowningDrowning is death from suffocation caused by a liquid entering the lungs and preventing the absorption of oxygen leading to cerebral hypoxia and myocardial infarction...
,
stranglingStrangling is compression of the neck that may lead to unconsciousness or death by causing an increasingly hypoxic state in the brain. Fatal strangling typically occurs in cases of violence, accidents, and as the mechanism of suicide in hangings...
,
chokingChoking is the mechanical obstruction of the flow of air from the environment into the lungs. Choking prevents breathing, and can be partial or complete, with partial choking allowing some,although inadequate, flow of air into the lungs...
,
cardiac arrestA cardiac arrest, also known as cardiopulmonary arrest or circulatory arrest, is the abrupt cessation of normal circulation of the blood due to failure of the heart to contract effectively during systole....
, head trauma, and complications during general
anesthesiaAnesthesia, or anaesthesia , has traditionally meant the condition of having sensation blocked or temporarily taken away. This allows patients to undergo surgery and other procedures without the distress and pain they would otherwise experience...
. Treatment strategies for brain hypoxia vary depending on the original cause of injury.
Further reading
- An extensive review of mechanisms by which ischemia damages the nervous system has been published by Peter Lipton.
- Chang, Steven; Doty, James; Skirboll, Stephen; Steinberg, Gary. Cerebral ischemia . cgi.stanford.edu. URL last accessed February 26 2006.
- Ramirez, Robert; Gulli, Laith. Encyclopedia of Neurological Disorders: Hypoxia. health.enotes.com. URL last accessed February 26 2006. (PDF format)