Diffuse axonal injury
Encyclopedia
Diffuse axonal injury is one of the most common and devastating types of traumatic brain injury
, meaning that damage occurs over a more widespread area than in focal brain injury. DAI, which refers to extensive lesions in white matter
tracts, is one of the major causes of unconsciousness and persistent vegetative state
after head trauma. It occurs in about half of all cases of severe head trauma
and also occurs in moderate and mild brain injury
.
The outcome is frequently coma
, with over 90% of patients with severe DAI never regaining consciousness. Those who do wake up often remain significantly impaired.
Nowadays, other authors state that DAI can occur in every degree of severity from (very) mild or moderate to (very) severe. Concussion may be a milder type of diffuse axonal injury.
that occurs due to direct impact and deformation of the brain
, DAI is the result of traumatic
shearing forces that occur when the head is rapidly accelerated or decelerated, as may occur in auto accidents, falls, and assaults. It usually results from rotational forces or severe deceleration
. Vehicle accidents are the most frequent cause of DAI; it can also occur as the result of child abuse
such as in shaken baby syndrome
.
The major cause of damage in DAI is the disruption of axons, the neural processes that allow one neuron
to communicate with another. Tracts of axons, which appear white due to myelin
ation, are referred to as white matter
. Acceleration causes shearing injury, which refers to damage inflicted as tissue slides over other tissue. When the brain is accelerated, parts of differing densities and distances from the axis of rotation slide over one another, stretching axons that traverse junctions between areas of different density, especially at junctions between white and grey matter
. Two thirds of DAI lesions occur in areas where grey and white matter meet.
s typically exist in the white matter
of brains injured by DAI; these lesions vary in size from about 1–15 mm and are distributed in a characteristic way. DAI most commonly affects white matter in areas including the brain stem
, the corpus callosum
, and the cerebral hemisphere
s. The lobes of the brain
most likely to be injured are the frontal and temporal lobes. Other common locations for DAI include the white matter in the cerebral cortex
, the corpus callosum
, the superior cerebral peduncle
s, basal ganglia
, thalamus
, and deep hemispheric nuclei. These areas may be more easily damaged because of the difference in density between them and the rest of the brain.
s, which occur in response to the primary injury
(which occurs as the result of mechanical forces at the moment of trauma) and take place hours to days after the initial injury, are largely responsible for the damage to axons.
Though the processes involved in secondary brain injury are still poorly understood, it is now accepted that stretching of axons during injury causes physical disruption to and proteolytic
degradation of the cytoskeleton
. It also opens sodium channels in the axolemma
, which causes voltage-gated calcium channels to open and Ca2+ to flow into the cell. The intracellular presence of Ca2+ unleashes several different pathways, including activating phospholipase
s and proteolytic enzymes, damaging mitochondria and the cytoskeleton, and activating secondary messengers, which can lead to separation of the axon and death of the cell.
can be broken. It is thought that integrin
s connected to the extracellular matrix
outside the cell and to the cytoskeleton
within it can transmit forces from the matrix to the cytoskeleton and cause the latter to tear when the axon is stretched.
Misalignment of cytoskeletal elements after stretch injury can lead to tearing of the axon and death of the neuron. Axonal transport continues up to the point of the break in the cytoskeleton, but no further, leading to a buildup of transport products and local swelling at that point. When it becomes large enough, swelling can tear the axon at the site of the break in the cytoskeleton, causing it to draw back toward the cell body and form a bulb. This bulb is called a retraction ball, the hallmark of diffuse axonal injury.
When the axon is transected, Wallerian degeneration
, in which the part of the axon distal to the break degrades, takes place within one to two days after injury. The axolemma disintegrates, myelin breaks down and begins to detach from cells in an anterograde direction (from the body of the cell toward the end of the axon), and nearby cells begin phagocytic activity, engulfing debris.
occurs as well, causing the influx of Ca2+
into the cell and unleashing a variety of degrading processes. An increase in Ca2+ and Na+
levels and a drop in K+
levels is found within the axon directly after injury. Possible routes of Ca2+ entry include sodium channel
s, pores torn in the membrane during stretch, and failure of ATP-dependent transporters due to mechanical blockage or lack of energy. High levels of intracellular Ca2+, the major cause of post-injury cell damage, destroy mitochondria, contribute to the generation of reactive oxygen species
and trigger phospholipase
s and proteolytic enzyme
s that damage Na+ channels and degrade or alter the cytoskeleton and the axoplasm
. Excess Ca2+ can also lead to damage to the blood brain barrier and swelling of the brain.
One of the protein
s activated by the presence of calcium
in the cell is calpain
, a Ca2+-dependent non-lysosomal
protease
. About 15 minutes to half an hour after the onset of injury, a process called calpain-mediated spectrin proteolysis, or CMSP, begins to occur. Calpain breaks down a molecule called spectrin
, which holds the membrane onto the cytoskeleton, causing the formation of bleb
s and the breakdown of the cytoskeleton and the membrane, and ultimately the death of the cell. Other molecules that can be degraded by calpains are microtubule
subunits, microtubule-associated protein
s, and neurofilament
s.
Generally occurring one to six hours into the process of post-stretch injury, the presence of calcium in the cell initiates the caspase
cascade, a process in cell injury that usually leads to apoptosis
, or "cell suicide".
Mitochondria, dendrite
s, and parts of the cytoskeleton
damaged in the injury have a limited ability to heal and regenerate, a process which occurs over 2 or more weeks. After the injury, astrocyte
s can shrink, causing parts of the brain
to atrophy.
or the cerebral cortex
. MRI is more useful than CT for detecting characteristics of diffuse axonal injury in the subacute and chronic time frames. Newer studies such as Diffusion Tensor Imaging are able to demonstrate the degree of white matter fiber tract injury even when the standard MRI is negative. Since axonal damage in DAI is largely a result of secondary biochemical cascade
s, it has a delayed onset, so a person with DAI who initially appears well may deteriorate later. Thus injury is frequently more severe than is realized, and medical professionals should suspect DAI in any patients whose CT scans appear normal but who have symptoms like unconsciousness
.
MRI is more sensitive than CT scans, but MRI may also miss DAI, because it identifies the injury using signs of edema
, which may not be present.
DAI is classified into grades based on severity of the injury. In Grade I, widespread axonal damage is present but no focal abnormalities are seen. In Grade II, damage found in Grade I is present in addition to focal abnormalities, especially in the corpus callosum. Grade III damage encompasses both Grades I and II plus rostral brain stem
injury and often tears in the tissue.
DAI currently lacks a specific treatment beyond what is done for any type of head injury
, including stabilizing the patient and trying to limit increases in intracranial pressure
(ICP).
acts as a membrane sealant, and may serve to prevent the aforementioned devastating calcium influx. Rats treated with polyethylene glycol immediately following DAI induction showed no cytotoxic edema on diffusion weighted MRI 7 days later unlike controls.
Traumatic brain injury
Traumatic brain injury , also known as intracranial injury, occurs when an external force traumatically injures the brain. TBI can be classified based on severity, mechanism , or other features...
, meaning that damage occurs over a more widespread area than in focal brain injury. DAI, which refers to extensive lesions in white matter
White matter
White matter is one of the two components of the central nervous system and consists mostly of myelinated axons. White matter tissue of the freshly cut brain appears pinkish white to the naked eye because myelin is composed largely of lipid tissue veined with capillaries. Its white color is due to...
tracts, is one of the major causes of unconsciousness and persistent vegetative state
Persistent vegetative state
A persistent vegetative state is a disorder of consciousness in which patients with severe brain damage are in a state of partial arousal rather than true awareness. It is a diagnosis of some uncertainty in that it deals with a syndrome. After four weeks in a vegetative state , the patient is...
after head trauma. It occurs in about half of all cases of severe head trauma
Head injury
Head injury refers to trauma of the head. This may or may not include injury to the brain. However, the terms traumatic brain injury and head injury are often used interchangeably in medical literature....
and also occurs in moderate and mild brain injury
Acquired brain injury
An acquired brain injury is brain damage caused by events after birth, rather than as part of a genetic or congenital disorder such as fetal alcohol syndrome, perinatal illness or perinatal hypoxia. ABI can result in cognitive, physical, emotional, or behavioural impairments that lead to permanent...
.
The outcome is frequently coma
Coma
In medicine, a coma is a state of unconsciousness, lasting more than 6 hours in which a person cannot be awakened, fails to respond normally to painful stimuli, light or sound, lacks a normal sleep-wake cycle and does not initiate voluntary actions. A person in a state of coma is described as...
, with over 90% of patients with severe DAI never regaining consciousness. Those who do wake up often remain significantly impaired.
Nowadays, other authors state that DAI can occur in every degree of severity from (very) mild or moderate to (very) severe. Concussion may be a milder type of diffuse axonal injury.
Mechanism
Unlike brain traumaTraumatic brain injury
Traumatic brain injury , also known as intracranial injury, occurs when an external force traumatically injures the brain. TBI can be classified based on severity, mechanism , or other features...
that occurs due to direct impact and deformation of the brain
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,...
, DAI is the result of traumatic
Physical trauma
Trauma refers to "a body wound or shock produced by sudden physical injury, as from violence or accident." It can also be described as "a physical wound or injury, such as a fracture or blow." Major trauma can result in secondary complications such as circulatory shock, respiratory failure and death...
shearing forces that occur when the head is rapidly accelerated or decelerated, as may occur in auto accidents, falls, and assaults. It usually results from rotational forces or severe deceleration
Acceleration
In physics, acceleration is the rate of change of velocity with time. In one dimension, acceleration is the rate at which something speeds up or slows down. However, since velocity is a vector, acceleration describes the rate of change of both the magnitude and the direction of velocity. ...
. Vehicle accidents are the most frequent cause of DAI; it can also occur as the result of child abuse
Child abuse
Child abuse is the physical, sexual, emotional mistreatment, or neglect of a child. In the United States, the Centers for Disease Control and Prevention and the Department of Children And Families define child maltreatment as any act or series of acts of commission or omission by a parent or...
such as in shaken baby syndrome
Shaken baby syndrome
Shaken baby syndrome is a triad of medical symptoms: subdural hematoma, retinal hemorrhage, and brain swelling from which doctors, consistent with current medical understanding, infer child abuse caused by intentional shaking...
.
The major cause of damage in DAI is the disruption of axons, the neural processes that allow one neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
to communicate with another. Tracts of axons, which appear white due to myelin
Myelin
Myelin is a dielectric material that forms a layer, the myelin sheath, usually around only the axon of a neuron. It is essential for the proper functioning of the nervous system. Myelin is an outgrowth of a type of glial cell. The production of the myelin sheath is called myelination...
ation, are referred to as white matter
White matter
White matter is one of the two components of the central nervous system and consists mostly of myelinated axons. White matter tissue of the freshly cut brain appears pinkish white to the naked eye because myelin is composed largely of lipid tissue veined with capillaries. Its white color is due to...
. Acceleration causes shearing injury, which refers to damage inflicted as tissue slides over other tissue. When the brain is accelerated, parts of differing densities and distances from the axis of rotation slide over one another, stretching axons that traverse junctions between areas of different density, especially at junctions between white and grey matter
Grey matter
Grey matter is a major component of the central nervous system, consisting of neuronal cell bodies, neuropil , glial cells and capillaries. Grey matter contains neural cell bodies, in contrast to white matter, which does not and mostly contains myelinated axon tracts...
. Two thirds of DAI lesions occur in areas where grey and white matter meet.
Characteristics
LesionLesion
A lesion is any abnormality in the tissue of an organism , usually caused by disease or trauma. Lesion is derived from the Latin word laesio which means injury.- Types :...
s typically exist in the white matter
White matter
White matter is one of the two components of the central nervous system and consists mostly of myelinated axons. White matter tissue of the freshly cut brain appears pinkish white to the naked eye because myelin is composed largely of lipid tissue veined with capillaries. Its white color is due to...
of brains injured by DAI; these lesions vary in size from about 1–15 mm and are distributed in a characteristic way. DAI most commonly affects white matter in areas including the brain stem
Brain stem
In vertebrate anatomy the brainstem is the posterior 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...
, the corpus callosum
Corpus callosum
The corpus callosum , also known as the colossal commissure, is a wide, flat bundle of neural fibers beneath the cortex in the eutherian brain at the longitudinal fissure. It connects the left and right cerebral hemispheres and facilitates interhemispheric communication...
, and the cerebral hemisphere
Cerebral hemisphere
A cerebral hemisphere is one of the two regions of the eutherian brain that are delineated by the median plane, . The brain can thus be described as being divided into left and right cerebral hemispheres. Each of these hemispheres has an outer layer of grey matter called the cerebral cortex that is...
s. The lobes of the brain
Lobes of the brain
Brain lobes were originally a purely anatomical classification, but have been shown also to be related to different brain functions. The telencephalon , the largest portion of the human brain, is divided into lobes, but so is the cerebellum...
most likely to be injured are the frontal and temporal lobes. Other common locations for DAI include the white matter in the cerebral cortex
Cerebral cortex
The cerebral cortex is a sheet of neural tissue that is outermost to the cerebrum of the mammalian brain. It plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness. It is constituted of up to six horizontal layers, each of which has a different...
, the corpus callosum
Corpus callosum
The corpus callosum , also known as the colossal commissure, is a wide, flat bundle of neural fibers beneath the cortex in the eutherian brain at the longitudinal fissure. It connects the left and right cerebral hemispheres and facilitates interhemispheric communication...
, the superior cerebral peduncle
Cerebral peduncle
Mainly, the three common areas that give rise to the cerebral peduncles are the cortex, the spinal cord and the cerebellum. The cerebral peduncle, by most classifications, is everything in the mesencephalon except the tectum. The region includes the midbrain tegmentum, crus cerebri and pretectum...
s, basal ganglia
Basal ganglia
The basal ganglia are a group of nuclei of varied origin in the brains of vertebrates that act as a cohesive functional unit. They are situated at the base of the forebrain and are strongly connected with the cerebral cortex, thalamus and other brain areas...
, thalamus
Thalamus
The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...
, and deep hemispheric nuclei. These areas may be more easily damaged because of the difference in density between them and the rest of the brain.
Histological characteristics
DAI is characterized by axonal separation, in which the axon is torn at the site of stretch and the part distal to the tear degrades. While it was once thought that the main cause of axonal separation was tearing due to mechanical forces during the trauma, it is now understood that axons are not typically torn upon impact; rather, secondary biochemical cascadeBiochemical cascade
A biochemical cascade is a series of chemical reactions in which the products of one reaction are consumed in the next reaction. There are several important biochemical cascade reactions in biochemistry, including the enzymatic cascades, such as the coagulation cascade and the complement system,...
s, which occur in response to the primary injury
Primary and secondary brain injury
Primary and secondary brain injury are ways to classify the injury processes that occur in brain injury. In traumatic brain injury , primary injury occurs during the initial insult, and results from displacement of the physical structures of the brain. On the other hand, secondary injury occurs...
(which occurs as the result of mechanical forces at the moment of trauma) and take place hours to days after the initial injury, are largely responsible for the damage to axons.
Though the processes involved in secondary brain injury are still poorly understood, it is now accepted that stretching of axons during injury causes physical disruption to and proteolytic
Proteolysis
Proteolysis is the directed degradation of proteins by cellular enzymes called proteases or by intramolecular digestion.-Purposes:Proteolysis is used by the cell for several purposes...
degradation of the cytoskeleton
Cytoskeleton
The cytoskeleton is a cellular "scaffolding" or "skeleton" contained within a cell's cytoplasm and is made out of protein. The cytoskeleton is present in all cells; it was once thought to be unique to eukaryotes, but recent research has identified the prokaryotic cytoskeleton...
. It also opens sodium channels in the axolemma
Axolemma
The axolemma is the cell membrane surrounding an axon. It is responsible for maintaining the membrane potential of the neuron, and it contains ion channels through which ions can flow. When this occurs, the voltage inside the axon changes, and depolarization or hyperpolarization of the membrane can...
, which causes voltage-gated calcium channels to open and Ca2+ to flow into the cell. The intracellular presence of Ca2+ unleashes several different pathways, including activating phospholipase
Phospholipase
A phospholipase is an enzyme that hydrolyzes phospholipids into fatty acids and other lipophilic substances. There are four major classes, termed A, B, C and D, distinguished by the type of reaction which they catalyze:*Phospholipase A...
s and proteolytic enzymes, damaging mitochondria and the cytoskeleton, and activating secondary messengers, which can lead to separation of the axon and death of the cell.
Cytoskeleton disruption
Axons are normally elastic, but when rapidly stretched they become brittle, and the axonal cytoskeletonCytoskeleton
The cytoskeleton is a cellular "scaffolding" or "skeleton" contained within a cell's cytoplasm and is made out of protein. The cytoskeleton is present in all cells; it was once thought to be unique to eukaryotes, but recent research has identified the prokaryotic cytoskeleton...
can be broken. It is thought that integrin
Integrin
Integrins are receptors that mediate attachment between a cell and the tissues surrounding it, which may be other cells or the ECM. They also play a role in cell signaling and thereby regulate cellular shape, motility, and the cell cycle....
s connected to the extracellular matrix
Extracellular matrix
In biology, the extracellular matrix is the extracellular part of animal tissue that usually provides structural support to the animal cells in addition to performing various other important functions. The extracellular matrix is the defining feature of connective tissue in animals.Extracellular...
outside the cell and to the cytoskeleton
Cytoskeleton
The cytoskeleton is a cellular "scaffolding" or "skeleton" contained within a cell's cytoplasm and is made out of protein. The cytoskeleton is present in all cells; it was once thought to be unique to eukaryotes, but recent research has identified the prokaryotic cytoskeleton...
within it can transmit forces from the matrix to the cytoskeleton and cause the latter to tear when the axon is stretched.
Misalignment of cytoskeletal elements after stretch injury can lead to tearing of the axon and death of the neuron. Axonal transport continues up to the point of the break in the cytoskeleton, but no further, leading to a buildup of transport products and local swelling at that point. When it becomes large enough, swelling can tear the axon at the site of the break in the cytoskeleton, causing it to draw back toward the cell body and form a bulb. This bulb is called a retraction ball, the hallmark of diffuse axonal injury.
When the axon is transected, Wallerian degeneration
Wallerian degeneration
Wallerian degeneration is a process that results when a nerve fiber is cut or crushed, in which the part of the axon separated from the neuron's cell body degenerates distal to the injury. This is also known as anterograde degeneration, or orthograde degeneration...
, in which the part of the axon distal to the break degrades, takes place within one to two days after injury. The axolemma disintegrates, myelin breaks down and begins to detach from cells in an anterograde direction (from the body of the cell toward the end of the axon), and nearby cells begin phagocytic activity, engulfing debris.
Calcium influx
While sometimes only the cytoskeleton is disturbed, frequently disruption of the axolemmaAxolemma
The axolemma is the cell membrane surrounding an axon. It is responsible for maintaining the membrane potential of the neuron, and it contains ion channels through which ions can flow. When this occurs, the voltage inside the axon changes, and depolarization or hyperpolarization of the membrane can...
occurs as well, causing the influx of Ca2+
Calcium
Calcium 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 gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
into the cell and unleashing a variety of degrading processes. An increase in Ca2+ and Na+
Sodium
Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...
levels and a drop in K+
Potassium
Potassium is the chemical element with the symbol K and atomic number 19. Elemental potassium is a soft silvery-white alkali metal that oxidizes rapidly in air and is very reactive with water, generating sufficient heat to ignite the hydrogen emitted in the reaction.Potassium and sodium are...
levels is found within the axon directly after injury. Possible routes of Ca2+ entry include sodium channel
Sodium ion channel
Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions through a cell's plasma membrane. They are classified according to the trigger that opens the channel for such ions, i.e...
s, pores torn in the membrane during stretch, and failure of ATP-dependent transporters due to mechanical blockage or lack of energy. High levels of intracellular Ca2+, the major cause of post-injury cell damage, destroy mitochondria, contribute to the generation of reactive oxygen species
Reactive oxygen species
Reactive oxygen species are chemically reactive molecules containing oxygen. Examples include oxygen ions and peroxides. Reactive oxygen species are highly reactive due to the presence of unpaired valence shell electrons....
and trigger phospholipase
Phospholipase
A phospholipase is an enzyme that hydrolyzes phospholipids into fatty acids and other lipophilic substances. There are four major classes, termed A, B, C and D, distinguished by the type of reaction which they catalyze:*Phospholipase A...
s and proteolytic enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s that damage Na+ channels and degrade or alter the cytoskeleton and the axoplasm
Axoplasm
Axoplasm is the cytoplasm within the axon of a neuron. Neural processes contain about 99.6% of the cell’s cytoplasm, and 99.7% of that is in the axons....
. Excess Ca2+ can also lead to damage to the blood brain barrier and swelling of the brain.
One of the protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s activated by the presence of calcium
Calcium
Calcium 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 gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
in the cell is calpain
Calpain
A calpain is a protein belonging to the 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...
, a Ca2+-dependent non-lysosomal
Lysosome
thumb|350px|Schematic of typical animal cell, showing subcellular components. [[Organelle]]s: [[nucleoli]] [[cell nucleus|nucleus]] [[ribosomes]] [[vesicle |vesicle]] rough [[endoplasmic reticulum]]...
protease
Protease
A protease is any enzyme that conducts proteolysis, that is, begins protein catabolism by hydrolysis of the peptide bonds that link amino acids together in the polypeptide chain forming the protein....
. About 15 minutes to half an hour after the onset of injury, a process called calpain-mediated spectrin proteolysis, or CMSP, begins to occur. Calpain breaks down a molecule called spectrin
Spectrin
Spectrin is a cytoskeletal protein that lines the intracellular side of the plasma membrane of many cell types in pentagonal or hexagonal arrangements, forming a scaffolding and playing an important role in maintenance of plasma membrane integrity and cytoskeletal structure...
, which holds the membrane onto the cytoskeleton, causing the formation of bleb
Bleb (medicine)
In medicine, a bleb is a large blister filled with serous fluid. Blebs can form in a number of tissues due to different pathologies, including frostbitten tissues, and as a cause of spontaneous pneumothorax. In the lungs, a bleb is a collection of air within the layers of the visceral pleura...
s and the breakdown of the cytoskeleton and the membrane, and ultimately the death of the cell. Other molecules that can be degraded by calpains are microtubule
Microtubule
Microtubules are a component of the cytoskeleton. These rope-like polymers of tubulin can grow as long as 25 micrometers and are highly dynamic. The outer diameter of microtubule is about 25 nm. Microtubules are important for maintaining cell structure, providing platforms for intracellular...
subunits, microtubule-associated protein
Microtubule-associated protein
In cell biology, microtubule-associated proteins are proteins that interact with the microtubules of the cellular cytoskeleton.-Function:...
s, and neurofilament
Neurofilament
Neurofilaments are the 10 nanometer intermediate filaments found specifically in neurons. They are a major component of the cell's cytoskeleton, and provide support for normal axonal radial growth...
s.
Generally occurring one to six hours into the process of post-stretch injury, the presence of calcium in the cell initiates the caspase
Caspase
Caspases, or cysteine-aspartic proteases or cysteine-dependent aspartate-directed proteases are a family of cysteine proteases that play essential roles in apoptosis , necrosis, and inflammation....
cascade, a process in cell injury that usually leads to apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
, or "cell suicide".
Mitochondria, dendrite
Dendrite
Dendrites are the branched projections of a neuron that act to conduct the electrochemical stimulation received from other neural cells to the cell body, or soma, of the neuron from which the dendrites project...
s, and parts of the cytoskeleton
Cytoskeleton
The cytoskeleton is a cellular "scaffolding" or "skeleton" contained within a cell's cytoplasm and is made out of protein. The cytoskeleton is present in all cells; it was once thought to be unique to eukaryotes, but recent research has identified the prokaryotic cytoskeleton...
damaged in the injury have a limited ability to heal and regenerate, a process which occurs over 2 or more weeks. After the injury, astrocyte
Astrocyte
Astrocytes , also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord...
s can shrink, causing parts of the brain
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,...
to atrophy.
Diagnosis and treatment
DAI is difficult to detect since it does not show up well on CT scans or with other macroscopic imaging techniques, though it shows up microscopically. However, there are characteristics typical of DAI that may or may not show up on a CT scan. Diffuse injury has more microscopic injury than macroscopic injury and is difficult to detect with CT and MRI, but its presence can be inferred when small bleeds are visible in the corpus callosumCorpus callosum
The corpus callosum , also known as the colossal commissure, is a wide, flat bundle of neural fibers beneath the cortex in the eutherian brain at the longitudinal fissure. It connects the left and right cerebral hemispheres and facilitates interhemispheric communication...
or the cerebral cortex
Cerebral cortex
The cerebral cortex is a sheet of neural tissue that is outermost to the cerebrum of the mammalian brain. It plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness. It is constituted of up to six horizontal layers, each of which has a different...
. MRI is more useful than CT for detecting characteristics of diffuse axonal injury in the subacute and chronic time frames. Newer studies such as Diffusion Tensor Imaging are able to demonstrate the degree of white matter fiber tract injury even when the standard MRI is negative. Since axonal damage in DAI is largely a result of secondary biochemical cascade
Biochemical cascade
A biochemical cascade is a series of chemical reactions in which the products of one reaction are consumed in the next reaction. There are several important biochemical cascade reactions in biochemistry, including the enzymatic cascades, such as the coagulation cascade and the complement system,...
s, it has a delayed onset, so a person with DAI who initially appears well may deteriorate later. Thus injury is frequently more severe than is realized, and medical professionals should suspect DAI in any patients whose CT scans appear normal but who have symptoms like unconsciousness
Unconsciousness
Unconsciousness is the condition of being not conscious—in a 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 a type of unconsciousness. Fainting due to a drop in blood pressure and a...
.
MRI is more sensitive than CT scans, but MRI may also miss DAI, because it identifies the injury using signs of edema
Edema
Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...
, which may not be present.
DAI is classified into grades based on severity of the injury. In Grade I, widespread axonal damage is present but no focal abnormalities are seen. In Grade II, damage found in Grade I is present in addition to focal abnormalities, especially in the corpus callosum. Grade III damage encompasses both Grades I and II plus rostral brain stem
Brain stem
In vertebrate anatomy the brainstem is the posterior 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...
injury and often tears in the tissue.
DAI currently lacks a specific treatment beyond what is done for any type of head injury
Head injury
Head injury refers to trauma of the head. This may or may not include injury to the brain. However, the terms traumatic brain injury and head injury are often used interchangeably in medical literature....
, including stabilizing the patient and trying to limit increases in intracranial pressure
Intracranial pressure
Intracranial pressure is the pressure inside the skull and thus in the brain tissue and cerebrospinal fluid . The body has various mechanisms by which it keeps the ICP stable, with CSF pressures varying by about 1 mmHg in normal adults through shifts in production and absorption of CSF...
(ICP).
Potential Treatments
Polyethylene glycolPolyethylene glycol
Polyethylene glycol is a polyether compound with many applications from industrial manufacturing to medicine. It has also been known as polyethylene oxide or polyoxyethylene , depending on its molecular weight, and under the tradename Carbowax.-Available forms:PEG, PEO, or POE refers to an...
acts as a membrane sealant, and may serve to prevent the aforementioned devastating calcium influx. Rats treated with polyethylene glycol immediately following DAI induction showed no cytotoxic edema on diffusion weighted MRI 7 days later unlike controls.
History
The idea of DAI first came about as a result of studies by Sabina Strich on lesions of the white matter of individuals who had suffered head trauma years before. Strich first proposed the idea in 1956, calling it diffuse degeneration of white matter, but that was too long so they just call it, "Diffuse axonal injury", or DAI for short. Strich was researching the relationship between dementia and head trauma and asserted in 1956 that DAI played an integral role in the eventual development of dementia due to head trauma. The term DAI was introduced in the early 1980s.External links
- Diffuse Axonal Injury MRI and CT Images