Brain ischemia is a condition in which there is insufficient bloodflow to the brain to meet metabolic demand. This leads to poor oxygen supply or cerebral hypoxia and thus leads to the death of brain tissue or cerebral infarction/ ischemic stroke. 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 consci ...

and

intracerebral hemorrhage Intracerebral hemorrhage (ICH), also known as cerebral bleed, intraparenchymal bleed, and hemorrhagic stroke, or haemorrhagic stroke, is a sudden bleeding into Intraparenchymal hemorrhage, the tissues of the brain, into its Intraventricular hemor ...

. 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 Speech is a human vocal communication using language. Each language uses phonetic combinations of vowel and consonant sounds that form the sound of its words (that is, all English words sound different from all French words, even if they are th ...

. 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 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 functionin ...

, 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 in a v ...

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 b ...

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, vertigo, double vision, or weakness on both sides of the body . Other symptoms include difficulty speaking, slurred speech, and the

loss of coordination Ataxia is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in eye movements. Ataxia is a clinical manifestation indicating dysfunction of ...

. 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 occurs, the symptoms may be permanent. Similar to cerebral hypoxia, severe or prolonged brain ischemia will result in unconsciousness,

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 ...

or death, 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, 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 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 has also been identified as a potential cause for brain ischemia. Moyamoya disease is an extremely rare cerebrovascular condition that limits blood

circulation Circulation may refer to: Science and technology * Atmospheric circulation, the large-scale movement of air * Circulation (physics), the path integral of the fluid velocity around a closed curve in a fluid flow field * Circulatory system, a bio ...

to the brain, consequently leading to oxygen deprivation.

Pathophysiology

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

substrate Substrate may refer to: Physical layers *Substrate (biology), the natural environment in which an organism lives, or the surface or medium on which an organism grows or is attached ** Substrate (locomotion), the surface over which an organism lo ...

. 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 (ATP) drop rapidly, approaching zero within 4 minutes. In the absence of biochemical energy, cells begin to lose the ability to maintain

electrochemical gradients An electrochemical gradient is a gradient of electrochemical potential, usually for an ion that can move across a membrane. The gradient consists of two parts, the chemical gradient, or difference in Concentration, solute concentration across a me ...

. Consequently, there is a massive influx of calcium 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 syn ...

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

protein synthesis Protein biosynthesis (or protein synthesis) is a core biological process, occurring inside Cell (biology), cells, homeostasis, balancing the loss of cellular proteins (via Proteolysis, degradation or Protein targeting, export) through the product ...

. 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. Th ...

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, 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 Cerebral circulation is the movement of blood through a network of cerebral arteries and cerebral veins, veins supplying the brain. The rate of cerebral blood flow in an adult human is typically 750 milliliters per minute, or about 15% of cardiac ...

. 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 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. If sufficient

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 A cerebral infarction is the pathologic process that results in an area of necrotic tissue in the brain (cerebral infarct). It is caused by disrupted blood supply ( ischemia) and restricted oxygen supply ( hypoxia), most commonly due to thromboemb ...

. The cerebral cortex 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 glutamate ...

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 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 Tissue Injury Biomarkers''- S100B, Glial fibrillary acidic protein,

enolase 2 Gamma-enolase, also known as enolase 2 (ENO2) or neuron specific enolase (NSE), is an enzyme that in humans is encoded by the ''ENO2'' gene. Gamma-enolase is a phosphopyruvate hydratase. Gamma-enolase is one of the three enolase isoenzymes found i ...

, Anti-NMDA receptor encephalitis. ''Inflammatory Biomarkers'' - c-reactive protein, Interleukin 6, Tumor necrosis factor α, VCAM-1. ''Coagulation / Thrombosis Biomarkers'' - Fibrinogen, D-dimer, 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 h ...

, 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 Hypoxemia is an abnormally low level of oxygen in the blood. More specifically, it is oxygen deficiency in artery, arterial blood. Hypoxemia has many causes, and often causes Hypoxia (medical), hypoxia as the blood is not supplying enough oxygen ...

and hypercapnia should be avoided. Seizures can induce more damage; accordingly, anticonvulsants should be prescribed and should a seizure occur, aggressive treatment should be undertaken.

Hyperglycaemia Hyperglycemia is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a blood sugar level higher than 11.1 mmol/L (200 mg/dL), but symptoms may not start to become noticeable until even ...

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 or

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 treatm ...

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 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 o ...

Brain 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 o ...

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, 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

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 t ...

. Potential causes of

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 i ...

, carbon monoxide poisoning, severe anemia, and use of drugs such as cocaine and other amphetamines. Other causes associated with brain hypoxia include drowning,

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 hanging ...

, choking, cardiac arrest, head trauma, 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