Experimental autoimmune encephalomyelitis
Encyclopedia
Experimental autoimmune encephalomyelitis, sometimes Experimental Allergic Encephalomyelitis (EAE) is an animal model of brain
inflammation
. It is an inflammatory demyelinating disease of the central nervous system (CNS). It is mostly used with rodent
s and is widely studied as an animal model of the human CNS demyelinating diseases, including the disease
s multiple sclerosis
and acute disseminated encephalomyelitis
(ADEM). EAE is also the prototype for T-cell-mediated autoimmune disease in general.
EAE was motivated by observations during the convalescence
from viral
diseases by Thomas M. Rivers, D. H. Sprunt and G. P. Berry in 1933. Their findings upon a transfer of inflamed patient tissue to primate
s was published in the Journal of Experimental Medicine
article (Vol. 58, No. 1, pp. 39–56). An acute monophasic illness, it has been suggested that EAE is far more similar to ADEM than MS.
EAE can be induced in a number of species, including mice, rats, guinea pigs, rabbits and primates. The most commonly used antigens in rodents are spinal cord homogenate (SCH), purified myelin, myelin protein such as MBP, PLP and MOG
, or peptides of these proteins, all resulting in distinct models with different disease characteristics regarding both immunology and pathology . It may also be induced by the passive transfer of T cells specifically reactive to these myelin antigens.
Depending on the antigen used and the genetic make-up of the animal, rodents can display a monophasic bout of EAE, a relapsing-remitting form , or chronic EAE . The typical susceptible rodent will debut with clinical symptoms around two weeks after immunization and present with a relapsing-remitting disease. The archetypical first clinical symptom is weakness of tail tonus that progresses to paralysis of the tail, followed by a progression up the body to affect the hind limbs and finally the forelimbs. However, similar to MS, the disease symptoms reflect the anatomical location of the inflammatory lesions, and may also include emotional liability, sensory loss, optic neuritis, difficulties with coordination and balance (ataxia), and muscle weakness and spasms. Recovery from symptoms can be complete or partial and the time varies with symptoms and disease severity. Depending on the relapse-remission intervals, rats can have up to 3 bouts of disease within an experimental period.
), or peptides from such protein emulsified in an adjuvant such as complete Freund's adjuvant
. The presence of the adjuvant allows the generation of inflammatory responses to the protein/peptides. In many protocols, mice are coinjected with pertussis toxin to break down the Blood-brain barrier
and allow immune cells access to the CNS tissue. This immunisation leads to multiple small disseminated lesions of demyelination (as well as micro-necroses) in the brain and spinal cord and the onset of clinical symptoms.
Although sharing some features, mostly demyelination, this model, first introduced in 1930s, differs from human MS in several ways. EAE either kills animals or leaves them with permanent disabilities, animals with EAE also suffer severe nerve inflammation, and the time course of EAE is entirely different from MS, being the main antigen (MBP) in charge.
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
. It is an inflammatory demyelinating disease of the central nervous system (CNS). It is mostly used with rodent
Rodent
Rodentia is an order of mammals also known as rodents, characterised by two continuously growing incisors in the upper and lower jaws which must be kept short by gnawing....
s and is widely studied as an animal model of the human CNS demyelinating diseases, including the disease
Disease
A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...
s multiple sclerosis
Multiple sclerosis
Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...
and acute disseminated encephalomyelitis
Acute disseminated encephalomyelitis
Acute disseminated encephalomyelitis is an immune mediated disease of the brain. It usually occurs following a viral infection but may appear following vaccination, bacterial or parasitic infection, or even appear spontaneously. As it involves autoimmune demyelination, it is similar to multiple...
(ADEM). EAE is also the prototype for T-cell-mediated autoimmune disease in general.
EAE was motivated by observations during the convalescence
Convalescence
Convalescence is the gradual recovery and of health and strength after illness. It refers to the later stage of an infectious disease or illness when the patient recovers and returns to normal, but may continue to be a source of infection even if feeling better...
from viral
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
diseases by Thomas M. Rivers, D. H. Sprunt and G. P. Berry in 1933. Their findings upon a transfer of inflamed patient tissue to primate
Primate
A primate is a mammal of the order Primates , which contains prosimians and simians. Primates arose from ancestors that lived in the trees of tropical forests; many primate characteristics represent adaptations to life in this challenging three-dimensional environment...
s was published in the Journal of Experimental Medicine
Journal of Experimental Medicine
The Journal of Experimental Medicine is a peer-reviewed academic journal published by the Rockefeller University Press that publishes research papers and commentaries on the physiological, pathological, and molecular mechanisms that encompass the host response to disease...
article (Vol. 58, No. 1, pp. 39–56). An acute monophasic illness, it has been suggested that EAE is far more similar to ADEM than MS.
EAE can be induced in a number of species, including mice, rats, guinea pigs, rabbits and primates. The most commonly used antigens in rodents are spinal cord homogenate (SCH), purified myelin, myelin protein such as MBP, PLP and MOG
Myelin oligodendrocyte glycoprotein
Myelin Oligodendrocyte Glycoprotein ' is a glycoprotein believed to be important in the process of myelinization of nerves in the central nervous system . In humans this protein is encoded by the MOG gene...
, or peptides of these proteins, all resulting in distinct models with different disease characteristics regarding both immunology and pathology . It may also be induced by the passive transfer of T cells specifically reactive to these myelin antigens.
Depending on the antigen used and the genetic make-up of the animal, rodents can display a monophasic bout of EAE, a relapsing-remitting form , or chronic EAE . The typical susceptible rodent will debut with clinical symptoms around two weeks after immunization and present with a relapsing-remitting disease. The archetypical first clinical symptom is weakness of tail tonus that progresses to paralysis of the tail, followed by a progression up the body to affect the hind limbs and finally the forelimbs. However, similar to MS, the disease symptoms reflect the anatomical location of the inflammatory lesions, and may also include emotional liability, sensory loss, optic neuritis, difficulties with coordination and balance (ataxia), and muscle weakness and spasms. Recovery from symptoms can be complete or partial and the time varies with symptoms and disease severity. Depending on the relapse-remission intervals, rats can have up to 3 bouts of disease within an experimental period.
EAE in mice
Demyelination is produced by injection of brain extracts, CNS proteins (such as myelin basic proteinMyelin basic protein
Myelin basic protein is a protein believed to be important in the process of myelination of nerves in the central nervous system .MBP was initially sequenced in 1971 after isolation from myelin membranes...
), or peptides from such protein emulsified in an adjuvant such as complete Freund's adjuvant
Freund's adjuvant
Freund's adjuvant is a solution of antigen emulsified in mineral oil and used as an immunopotentiator . The complete form, Freund's Complete Adjuvant, is composed of inactivated and dried mycobacteria , whereas the incomplete form lacks the mycobacterial components...
. The presence of the adjuvant allows the generation of inflammatory responses to the protein/peptides. In many protocols, mice are coinjected with pertussis toxin to break down the Blood-brain barrier
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...
and allow immune cells access to the CNS tissue. This immunisation leads to multiple small disseminated lesions of demyelination (as well as micro-necroses) in the brain and spinal cord and the onset of clinical symptoms.
Although sharing some features, mostly demyelination, this model, first introduced in 1930s, differs from human MS in several ways. EAE either kills animals or leaves them with permanent disabilities, animals with EAE also suffer severe nerve inflammation, and the time course of EAE is entirely different from MS, being the main antigen (MBP) in charge.