pathology Pathology is the study of the causes and effects of disease or injury. The word ''pathology'' also refers to the study of disease in general, incorporating a wide range of biology research fields and medical practices. However, when used in t ...

and

anatomy Anatomy () is the branch of biology concerned with the study of the structure of organisms and their parts. Anatomy is a branch of natural science that deals with the structural organization of living things. It is an old science, having it ...

the penumbra is the area surrounding an

ischemic Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems wi ...

event such as thrombotic or embolic

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 ...

. Immediately following the event, blood flow and therefore

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 as well ...

transport is reduced locally, leading to hypoxia of the cells near the location of the original insult. This can lead to hypoxic cell death (

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 the ...

) and amplify the original damage from the

ischemia Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems w ...

; however, the penumbra area may remain viable for several hours after an ischemic event due to the collateral arteries that supply the penumbral zone. As time elapses after the onset of stroke, the extent of the penumbra tends to decrease; therefore, in the

emergency department An emergency department (ED), also known as an accident and emergency department (A&E), emergency room (ER), emergency ward (EW) or casualty department, is a medical treatment facility specializing in emergency medicine, the acute care of pat ...

a major concern is to protect the penumbra by increasing oxygen transport and delivery to cells in the danger zone, thereby limiting cell death. The existence of a penumbra implies that salvage of the cells is possible. There is a high correlation between the extent of spontaneous neurological recovery and the volume of penumbra that escapes infarction; therefore, saving the penumbra should improve the clinical outcome.

Definition

One widely accepted definition for penumbra describes the area as "ischemic tissue potentially destined for infarction but it isn't irreversibly injured and the target of any acute therapies." The original definition of the penumbra referred to areas of the brain that were damaged but not yet dead, and offered promise to rescue the brain tissue with the appropriate therapies.

Blood flow

The penumbra region typically occurs when blood flow drops below 20 mL/100 g/min. At this point electrical communication between

neurons A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...

fails to exist. Cells in this region are alive but metabolic pumps are inhibited,

oxidative metabolism Cellular respiration is the process by which biological fuels are oxidised in the presence of an inorganic electron acceptor such as oxygen to produce large amounts of energy, to drive the bulk production of ATP. Cellular respiration may be des ...

is reduced but

may begin to depolarize again. Areas of the brain generally do not become

infarcted 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 the ...

until blood flow to the region drops below 10 to 12 mL/100 g/min. At this point,

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 ...

release becomes unregulated,

ion pumps An ion pump (also referred to as a sputter ion pump) is a type of vacuum pump which operates by sputtering a metal getter. Under ideal conditions, ion pumps are capable of reaching pressures as low as 10−11 mbar. An ion pump first ionizes ga ...

are inhibited and adenosine triphosphate (ATP) synthesis also stops which ultimately leads to the disruption of

intracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...

processes and neuronal death.

Identification by imaging

Positron emission tomography Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in metabolic processes, and in other physiological activities including blood flow, ...

(PET) can quantify the size of the penumbra, but is neither widely available nor rapidly accessible.

Magnetic resonance imaging Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio waves ...

can estimate the size of the penumbra with a combination of two

MRI sequences An MRI sequence in magnetic resonance imaging (MRI) is a particular setting of pulse sequences and pulsed field gradients, resulting in a particular image appearance. A multiparametric MRI is a combination of two or more sequences, and/or includi ...

: *

Perfusion weighted imaging Perfusion MRI or perfusion-weighted imaging (PWI) is perfusion scanning by the use of a particular MRI sequence. The acquired data are then post-processed to obtain perfusion maps with different parameters, such as BV (blood volume), BF (blood fl ...

(PWI) shows decreased blood perfusion in the infarcted core and the penumbra *

Diffusion weighted imaging Diffusion-weighted magnetic resonance imaging (DWI or DW-MRI) is the use of specific MRI sequences as well as software that generates images from the resulting data that uses the diffusion of water molecules to generate contrast in MR images. It ...

(DWI) can estimate the size of the infarcted core. Both of these sequences somewhat overestimates their volumes of interest, but the size of the penumbra can roughly be estimated by subtracting abnormal volume by DWI from abnormal volume by PWI. The penumbral area can also be detected based upon an integration of three factors. These factors include: the site of vessel occlusion, the extent of oligaemia ( hypoperfused area surrounding the penumbra, but not at risk of infarction ) at that moment, and the mismatch between this

perfusion Perfusion is the passage of fluid through the circulatory system or lymphatic system to an organ or a tissue, usually referring to the delivery of blood to a capillary bed in tissue. Perfusion is measured as the rate at which blood is deliver ...

defect and the area of the brain already infarcted.

Clinical relevance

A higher volume of penumbra around a

cerebral 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 ...

means a greater volume of potentially salvageable brain matter by

thrombolysis Thrombolysis, also called fibrinolytic therapy, is the breakdown (lysis) of blood clots formed in blood vessels, using medication. It is used in ST elevation myocardial infarction, stroke, and in cases of severe venous thromboembolism (massive ...

and

thrombectomy Mechanical thrombectomy, or simply thrombectomy, is the interventional procedure of removing a blood clot (thrombus) from a blood vessel. It is commonly performed in the cerebral arteries ( interventional neuroradiology). The effectiveness of thro ...

. Such therapies have a greater effect on regaining functions such as movement after a cerebral infarction. After the initial ischemic event the penumbra transitions from a

tissue remodeling Tissue remodeling is the reorganization or renovation of existing tissues. Tissue remodeling can be either physiological or pathological. The process can either change the characteristics of a tissue such as in blood vessel remodeling, or result i ...

characterized by damage to a remodeling characterized by repair. In the penumbra,

microglia Microglia are a type of neuroglia (glial cell) located throughout the brain and spinal cord. Microglia account for about 7% of cells found within the brain. As the resident macrophage cells, they act as the first and main form of active immune de ...

are thought to exert neuroprotective effects via specialized contacts with neuronal somata, termed somatic junctions. Understanding and supporting these microglial actions could broaden the therapeutic window and lead to higher amount of preserved

nervous tissue Nervous tissue, also called neural tissue, is the main tissue component of the nervous system. The nervous system regulates and controls body functions and activity. It consists of two parts: the central nervous system (CNS) comprising the brain ...

History

The first decade of research focused on physiologic profile of the penumbra tissue after

, mapping the cerebral blood flow, and quantifying oxygen and glucose consumption to define these areas. The second decade revealed the mechanism of the neuronal cell death. As the Biochemical pathways were dissected penumbral science became a rapidly evolving area of molecular biology. The third decade of penumbral research found a transitional leap as using

positron emission tomography Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in metabolic processes, and in other physiological activities including blood flow, ...

(PET) scanning can identify brain tissue with decreased blood flow and

magnetic resonance imaging Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio waves ...

(MRI) has the ability to detect portions of the ischemic tissue that has not yet died. These images have allowed vision into the brain to see the areas of tissue that may be salvaged, the penumbra.

References

* http://www.neurology.org/content/51/3_Suppl_3/S44.short {{DEFAULTSORT:Penumbra (Medicine) Cardiovascular diseases