Brain ischemia is a condition in which there is insufficient bloodflow to the

brain A brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as Visual perception, vision. I ...

to meet metabolic demand. This leads to poor oxygen supply or

cerebral hypoxia Cerebral hypoxia is a form of hypoxia (reduced supply of oxygen), specifically involving the brain; when the brain is completely deprived of oxygen, it is called ''cerebral anoxia''. There are four categories of cerebral hypoxia; they are, in ...

and thus leads to the death of brain tissue or cerebral infarction/

ischemic stroke A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop funct ...

. It is a sub-type of stroke along with

subarachnoid hemorrhage Subarachnoid hemorrhage (SAH) is bleeding into the subarachnoid space—the area between the arachnoid membrane and the pia mater surrounding the brain. Symptoms may include a severe headache of rapid onset, vomiting, decreased level of cons ...

and

intracerebral hemorrhage Intracerebral hemorrhage (ICH), also known as cerebral bleed, intraparenchymal bleed, and hemorrhagic stroke, or haemorrhagic stroke, is a sudden bleeding into the tissues of the brain, into its ventricles, or into both. It is one kind of bleed ...

. 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 of brain ischemia involve impairments in 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

stroke A stroke is a disease, medical condition in which poor cerebral circulation, blood flow to the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemorr ...

, cardiorespiratory arrest, and irreversible brain damage. An interruption of blood flow to the brain for more than 10 seconds causes unconsciousness, and an interruption in flow for more than a few minutes generally results in irreversible brain damage. In 1974, Hossmann and Zimmermann demonstrated that ischemia induced in

mammalian brain A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ i ...

s 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.

Symptoms and signs

The symptoms of brain ischemia reflect the anatomical region undergoing blood and oxygen deprivation. Ischemia within the arteries branching from the

internal carotid artery The internal carotid artery (Latin: arteria carotis interna) is an artery in the neck which supplies the anterior circulation of the brain. In human anatomy, the internal and external carotids arise from the common carotid arteries, where these ...

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 arteries in the back of the brain may result in symptoms such as

dizziness Dizziness is an imprecise term that can refer to a sense of disorientation in space, vertigo, or lightheadedness. It can also refer to disequilibrium or a non-specific feeling, such as giddiness or foolishness. Dizziness is a common medical c ...

vertigo Vertigo is a condition where a person has the sensation of movement or of surrounding objects moving when they are not. Often it feels like a spinning or swaying movement. This may be associated with nausea, vomiting, sweating, or difficulties w ...

, double vision, 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

infarction Infarction is tissue death ( necrosis) due to inadequate blood supply to the affected area. It may be caused by artery blockages, rupture, mechanical compression, or vasoconstriction. The resulting lesion is referred to as an infarct (from th ...

occurs, the symptoms may be permanent. Similar to

, severe or prolonged brain ischemia will result in

unconsciousness Unconsciousness is a state in which a living individual exhibits a complete, or near-complete, inability to maintain an awareness of self and environment or to respond to any human or environmental stimulus. Unconsciousness may occur as the r ...

brain damage Neurotrauma, brain damage or brain injury (BI) is the destruction or degeneration of brain cells. Brain injuries occur due to a wide range of internal and external factors. In general, brain damage refers to significant, undiscriminating t ...

death Death is the irreversible cessation of all biological functions that sustain an organism. For organisms with a brain, death can also be defined as the irreversible cessation of functioning of the whole brain, including brainstem, and brain ...

, mediated by the ischemic cascade. Multiple cerebral ischemic events may lead to subcortical ischemic depression, 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 tachycardia Ventricular tachycardia (V-tach or VT) is a fast heart rate arising from the lower chambers of the heart. Although a few seconds of VT may not result in permanent problems, longer periods are dangerous; and multiple episodes over a short period ...

, plaque buildup in the arteries, blood clots, extremely low blood pressure as a result of

heart attack A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which ma ...

, and congenital heart defects have a higher predisposition to brain ischemia in comparison to the average population. 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 events that may result in brain ischemia include cardiorespiratory arrest,

, and severe irreversible brain damage. Recently,

Moyamoya disease Moyamoya disease is a disease in which certain arteries in the brain are constricted. Blood flow is blocked by constriction and blood clots (thrombosis). A collateral circulation develops around the blocked vessels to compensate for the blockage, ...

has also been identified as a potential cause for brain ischemia. Moyamoya disease is an extremely rare cerebrovascular condition that limits blood circulation to the brain, consequently leading to oxygen deprivation.

Pathophysiology

During brain ischemia, the brain cannot perform aerobic metabolism due to the loss of

oxygen Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements ...

and substrate. The brain is not able to switch to anaerobic metabolism and, because it does not have any long term energy stored, the levels of

adenosine triphosphate Adenosine triphosphate (ATP) is an organic compound that provides energy to drive many processes in living cells, such as muscle contraction, nerve impulse propagation, condensate dissolution, and chemical synthesis. Found in all known forms ...

(ATP) drop rapidly, approaching zero within 4 minutes. In the absence of biochemical energy, cells begin to lose the ability to maintain electrochemical gradients. Consequently, there is a massive influx of

calcium Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar ...

into the cytosol, a massive release of

glutamate Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can synt ...

from synaptic vesicles, lipolysis, calpain activation, and the arrest of

protein synthesis Protein biosynthesis (or protein synthesis) is a core biological process, occurring inside cells, balancing the loss of cellular proteins (via degradation or export) through the production of new proteins. Proteins perform a number of critical ...

. Additionally, 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. An area called a

penumbra The umbra, penumbra and antumbra are three distinct parts of a shadow, created by any light source after impinging on an opaque object. Assuming no diffraction, for a collimated beam (such as a point source) of light, only the umbra is cast. T ...

may result, wherein neurons do not receive enough blood to communicate, however do receive sufficient oxygenation to avoid cell death for a short period of time.

Diagnosis

Classification

The broad term, "

" can be divided into three categories: brain ischemia,

and

. Brain ischemia can be further subdivided, by cause, into thrombotic,

embolic An embolism is the lodging of an embolus, a blockage-causing piece of material, inside a blood vessel. The embolus may be a blood clot (thrombus), a fat globule (fat embolism), a bubble of air or other gas (gas embolism), amniotic fluid (amniot ...

, 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 A thrombus (plural thrombi), colloquially called a blood clot, is the final product of the blood coagulation step in hemostasis. There are two components to a thrombus: aggregated platelets and red blood cells that form a plug, and a mesh of cr ...

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

thrombosis Thrombosis (from Ancient Greek "clotting") is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (th ...

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 arrest Cardiac arrest is when the heart suddenly and unexpectedly stops beating. It is a medical emergency that, without immediate medical intervention, will result in sudden cardiac death within minutes. Cardiopulmonary resuscitation (CPR) and possi ...

. If sufficient 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 injury. Reperfusion injury is classified as the damage that ensues after restoration of blood supply to ischemic tissue. Due to different susceptibility to ischemia of various brain regions, a global brain ischemia may cause focal brain infarction. The

cerebral cortex The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. The cerebral cortex mostly consists of the six-layered neocortex, with just 10% consisting o ...

and

striatum The striatum, or corpus striatum (also called the striate nucleus), is a nucleus (a cluster of neurons) in the subcortical basal ganglia of the forebrain. The striatum is a critical component of the motor and reward systems; receives gluta ...

are more susceptible than the thalamus, and the thalamus in turn is more sensitive than the brainstem. Partial cerebral cortex infarction from global brain ischemia typically manifests as watershed stroke.

Biomarker

Use of

biomarker In biomedical contexts, a biomarker, or biological marker, is a measurable indicator of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal biological processes, p ...

is one method that has been evaluated to predict the risk of stroke, diagnose stroke and its causes, predict stroke severity and outcome, and guide prevention therapy. Blood Biomarkers: Many proteins and RNA biomarkers identified are connected to ischemic stroke pathophysiology includes ''

Central Nervous System The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...

Tissue Injury Biomarkers''- S100B,

Glial fibrillary acidic protein Glial fibrillary acidic protein (GFAP) is a protein that is encoded by the ''GFAP'' gene in humans. It is a type III intermediate filament (IF) protein that is expressed by numerous cell types of the central nervous system (CNS), including astro ...

, enolase 2, Anti-NMDA receptor encephalitis. ''Inflammatory Biomarkers'' - c-reactive protein,

Interleukin 6 Interleukin 6 (IL-6) is an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine. In humans, it is encoded by the ''IL6'' gene. In addition, osteoblasts secrete IL-6 to stimulate osteoclast formation. Smooth ...

, Tumor necrosis factor α, VCAM-1. ''Coagulation /

Thrombosis Thrombosis (from Ancient Greek "clotting") is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (th ...

Biomarkers'' - Fibrinogen,

D-dimer D-dimer (or D dimer) is a fibrin degradation product (or FDP), a small protein fragment present in the blood after a blood clot is degraded by fibrinolysis. It is so named because it contains two D fragments of the fibrin protein joined by a cros ...

, Von Willebrand factor ''Other Biomarkers''-

PARK7 Protein deglycase DJ-1, also known as Parkinson disease protein 7, is a protein which in humans is encoded by the ''PARK7'' gene. Structure Gene The gene ''PARK7'', also known as ''DJ-1'', encodes a protein of the peptidase C56 family. The ...

, B-type neurotrophic growth factor.

Treatment

Alteplase (t-PA) is an effective medication for acute ischemic stroke. When given within 3 hours, treatment with tpa significantly improves the probability of a favourable outcome versus treatment with placebo. 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

hypercapnia Hypercapnia (from the Greek ''hyper'' = "above" or "too much" and ''kapnos'' = "smoke"), also known as hypercarbia and CO2 retention, is a condition of abnormally elevated carbon dioxide (CO2) levels in the blood. Carbon dioxide is a gaseous p ...

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 Anticoagulants, commonly known as blood thinners, are chemical substances that prevent or reduce coagulation of blood, prolonging the clotting time. Some of them occur naturally in blood-eating animals such as leeches and mosquitoes, where the ...

with

warfarin Warfarin, sold under the brand name Coumadin among others, is a medication that is used as an anticoagulant (blood thinner). It is commonly used to prevent blood clots such as deep vein thrombosis and pulmonary embolism, and to prevent st ...

heparin Heparin, also known as unfractionated heparin (UFH), is a medication and naturally occurring glycosaminoglycan. Since heparins depend on the activity of antithrombin, they are considered anticoagulants. Specifically it is also used in the treat ...

may be used if the patient has atrial fibrillation. Operative procedures such as carotid endarterectomy and carotid stenting may be performed if the patient has a significant amount of plaque in the carotid arteries associated with the local ischemic events.

Research

Therapeutic hypothermia 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 flow. If hypoxia lasts for long periods of time,

coma A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to respond normally to painful stimuli, light, or sound, lacks a normal wake-sleep cycle and does not initiate voluntary actions. Coma patients exhi ...

seizures An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with lo ...

, and even

brain death Brain death is the permanent, irreversible, and complete loss of brain function which may include cessation of involuntary activity necessary to sustain life. It differs from persistent vegetative state, in which the person is alive and some aut ...

may occur. Symptoms of brain hypoxia are similar to ischemia and include inattentiveness, poor judgment, memory loss, and a decrease in

motor coordination Motor coordination is the orchestrated movement of multiple body parts as required to accomplish intended actions, like walking. This coordination is achieved by adjusting kinematic and kinetic parameters associated with each body part involved in ...

. Potential causes of brain hypoxia are

suffocation Asphyxia or asphyxiation is a condition of deficient supply of oxygen to the body which arises from abnormal breathing. Asphyxia causes generalized hypoxia, which affects primarily the tissues and organs. There are many circumstances that can ...

carbon monoxide poisoning Carbon monoxide poisoning typically occurs from breathing in carbon monoxide (CO) at excessive levels. Symptoms are often described as " flu-like" and commonly include headache, dizziness, weakness, vomiting, chest pain, and confusion. Large ...

, severe

anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, t ...

, and use of drugs such as

cocaine Cocaine (from , from , ultimately from Quechua: ''kúka'') is a central nervous system (CNS) stimulant mainly used recreationally for its euphoric effects. It is primarily obtained from the leaves of two Coca species native to South Am ...

and other

amphetamines Substituted amphetamines are a class of compounds based upon the amphetamine structure; it includes all derivative compounds which are formed by replacing, or substituting, one or more hydrogen atoms in the amphetamine core structure with sub ...

. Other causes associated with brain hypoxia include

drowning Drowning is a type of suffocation induced by the submersion of the mouth and nose in a liquid. Most instances of fatal drowning occur alone or in situations where others present are either unaware of the victim's situation or unable to offer as ...

strangling Strangling 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 is one of two main ways that hangin ...

choking Choking, also known as foreign body airway obstruction (FBAO), is a phenomenon that occurs when breathing is impeded by a blockage inside of the respiratory tract. An obstruction that prevents oxygen from entering the lungs results in oxygen dep ...

head trauma A head injury is any injury that results in trauma to the skull or brain. The terms ''traumatic brain injury'' and ''head injury'' are often used interchangeably in the medical literature. Because head injuries cover such a broad scope of inju ...

, and complications during general

anesthesia Anesthesia is a state of controlled, temporary loss of sensation or awareness that is induced for medical or veterinary purposes. It may include some or all of analgesia (relief from or prevention of pain), paralysis (muscle relaxation), ...

. Treatment strategies for brain hypoxia vary depending on the original cause of injury, primary and/or secondary.

References

Bibliography

External links

{{Hemodynamics Vascular diseases Stroke Ischemia