Primary and secondary brain injury
Encyclopedia
Primary and secondary brain injury are ways to classify the injury processes that occur in brain injury
. In traumatic brain injury
(TBI), 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 gradually and may involve an array of cellular processes. Secondary injury, which is not caused by mechanical damage, can result from the primary injury or be independent of it. The fact that people sometimes deteriorate after brain injury was originally taken to mean that secondary injury was occurring. It is not well understood how much of a contribution primary and secondary injuries respectively have to the clinical manifestations of TBI.
Primary and secondary injuries occur in insults other than TBI as well, such as spinal cord injury
and stroke
.
In TBI, primary injuries result immediately from the initial trauma. Primary injury occurs at the moment of trauma and includes contusion, damage to blood vessel
s, and axonal shearing
, in which the axon
s of neuron
s are stretched and torn. The blood brain barrier and meninges
may be damaged in the primary injury, and neurons may die. Cells are killed in a nonspecific manner in primary injury. Tissues have a deformation threshold: if they are deformed past this threshold they are injured. Different regions in the brain may be more sensitive to mechanical loading due to differences in their properties that result from differences in their makeup; for example, myelin
ated tissues may have different properties than other tissues. Thus some tissues may experience more force and be more injured in the primary injury. The primary injury leads to the secondary injury.
, stroke, and traumatic brain injury
and involves metabolic
cascade
s.
Secondary injury can result from complications of the injury. These include ischemia
(insufficient blood flow); cerebral hypoxia
(insufficient oxygen in the brain); hypotension
(low blood pressure
); cerebral edema
(swelling of the brain); changes in the blood flow to the brain
; and raised intracranial pressure
(the pressure within the skull). If intracranial pressure gets too high, it can lead to deadly brain herniation
, in which parts of the brain are squeezed past structures in the skull.
Other secondary insults include hypercapnia
(excessive carbon dioxide levels in the blood), acidosis
(excessively acidic blood), meningitis
, and brain abscess
. In addition, alterations in the release of neurotransmitter
s (the chemicals used by brain cells to communicate) can cause secondary injury. Imbalances in some neurotransmitters can lead to excitotoxicity
, damage to brain cells that results from overactivation of biochemical receptors for excitatory neurotransmitters (those that increase the likelihood that a neuron
will fire
). Excitotoxicity can cause a variety of negative effects, including damage to cells by free radicals, potentially leading to neurodegeneration
. Another factor in secondary injury is loss of cerebral autoregulation, the ability of the brain's blood vessels to regulate cerebral blood flow
. Other factors in secondary damage are breakdown of the blood–brain barrier, edema, ischemia and hypoxia. Ischemia is one of the leading causes of secondary brain damage
after head trauma. Similar mechanisms are involved in secondary injury after ischemia, trauma, and injuries resulting when a person does not get enough oxygen. After stroke, an ischemic cascade
, a set of biochemical cascade
s takes place.
Thus efforts to reduce disability and death from TBI are thought to be best aimed at secondary injury, because the primary injury is thought to be irreversible.
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...
. In traumatic brain injury
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...
(TBI), 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 gradually and may involve an array of cellular processes. Secondary injury, which is not caused by mechanical damage, can result from the primary injury or be independent of it. The fact that people sometimes deteriorate after brain injury was originally taken to mean that secondary injury was occurring. It is not well understood how much of a contribution primary and secondary injuries respectively have to the clinical manifestations of TBI.
Primary and secondary injuries occur in insults other than TBI as well, such as spinal cord injury
Spinal cord injury
A spinal cord injury refers to any injury to the spinal cord that is caused by trauma instead of disease. Depending on where the spinal cord and nerve roots are damaged, the symptoms can vary widely, from pain to paralysis to incontinence...
and stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
.
Primary
| Primary | Secondary |
|---|---|
|
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... Metabolism Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories... Cerebral blood flow Cerebral blood flow, or CBF, is the blood supply to the brain in a given time. In an adult, CBF is typically 750 millitres per minute or 15% of the cardiac output. This equates to 50 to 54 millilitres of blood per 100 grams of brain tissue per minute. CBF is tightly regulated to meet the brain's... Excitotoxicity Excitotoxicity is the pathological process by which nerve cells are damaged and killed by excessive stimulation by neurotransmitters such as glutamate and similar substances. This occurs when receptors for the excitatory neurotransmitter glutamate such as the NMDA receptor and AMPA receptor are... |
In TBI, primary injuries result immediately from the initial trauma. Primary injury occurs at the moment of trauma and includes contusion, damage to blood vessel
Blood vessel
The blood vessels are the part of the circulatory system that transports blood throughout the body. There are three major types of blood vessels: the arteries, which carry the blood away from the heart; the capillaries, which enable the actual exchange of water and chemicals between the blood and...
s, and axonal shearing
Shear stress
A shear stress, denoted \tau\, , is defined as the component of stress coplanar with a material cross section. Shear stress arises from the force vector component parallel to the cross section...
, in which the axon
Axon
An axon is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body or soma....
s of 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...
s are stretched and torn. The blood brain barrier and meninges
Meninges
The meninges is the system of membranes which envelopes the central nervous system. The meninges consist of three layers: the dura mater, the arachnoid mater, and the pia mater. The primary function of the meninges and of the cerebrospinal fluid is to protect the central nervous system.-Dura...
may be damaged in the primary injury, and neurons may die. Cells are killed in a nonspecific manner in primary injury. Tissues have a deformation threshold: if they are deformed past this threshold they are injured. Different regions in the brain may be more sensitive to mechanical loading due to differences in their properties that result from differences in their makeup; for example, 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...
ated tissues may have different properties than other tissues. Thus some tissues may experience more force and be more injured in the primary injury. The primary injury leads to the secondary injury.
Secondary
Secondary injury is an indirect result of the insult. It results from processes initiated by the trauma. It occurs in the hours and days following the primary injury and plays a large role in the brain damage and death that results from TBI. Unlike in most forms of trauma a large percentage of the people killed by brain trauma do not die right away but rather days to weeks after the event. In addition, rather than improving after being hospitalized as most patients with other types of injuries do, about 40% of people with TBI deteriorate. This is often a result of secondary injury, which can damage even neurons that were unharmed in the primary injury. It occurs after a variety of brain insults including subarachnoid hemorrhageSubarachnoid hemorrhage
A subarachnoid hemorrhage , or subarachnoid haemorrhage in British English, is bleeding into the subarachnoid space—the area between the arachnoid membrane and the pia mater surrounding the brain...
, stroke, and traumatic brain injury
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...
and involves metabolic
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
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.
Secondary injury can result from complications of the injury. These include ischemia
Ischemia
In medicine, ischemia is a restriction in blood supply, generally due to factors in the blood vessels, with resultant damage or dysfunction of tissue. It may also be spelled ischaemia or ischæmia...
(insufficient blood flow); cerebral hypoxia
Hypoxia (medical)
Hypoxia, or hypoxiation, is a pathological condition in which the body as a whole or a region of the body is deprived of adequate oxygen supply. Variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise...
(insufficient oxygen in the brain); hypotension
Hypotension
In physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
(low blood pressure
Blood pressure
Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...
); cerebral edema
Cerebral edema
Cerebral edema or cerebral œdema is an excess accumulation of water in the intracellular or extracellular spaces of the brain.-Vasogenic:Due to a breakdown of tight endothelial junctions which make up the blood-brain barrier...
(swelling of the brain); changes in the blood flow to the brain
Cerebral blood flow
Cerebral blood flow, or CBF, is the blood supply to the brain in a given time. In an adult, CBF is typically 750 millitres per minute or 15% of the cardiac output. This equates to 50 to 54 millilitres of blood per 100 grams of brain tissue per minute. CBF is tightly regulated to meet the brain's...
; and raised 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...
(the pressure within the skull). If intracranial pressure gets too high, it can lead to deadly brain herniation
Brain herniation
Brain herniation, also known as cistern obliteration, is a deadly side effect of very high intracranial pressure that occurs when the brain shifts across structures within the skull...
, in which parts of the brain are squeezed past structures in the skull.
Other secondary insults include hypercapnia
Hypercapnia
Hypercapnia or hypercapnea , also known as hypercarbia, is a condition where there is too much carbon dioxide in the blood...
(excessive carbon dioxide levels in the blood), acidosis
Acidosis
Acidosis is an increased acidity in the blood and other body tissue . If not further qualified, it usually refers to acidity of the blood plasma....
(excessively acidic blood), meningitis
Meningitis
Meningitis is inflammation of the protective membranes covering the brain and spinal cord, known collectively as the meninges. The inflammation may be caused by infection with viruses, bacteria, or other microorganisms, and less commonly by certain drugs...
, and brain abscess
Brain abscess
Brain abscess is an abscess caused by inflammation and collection of infected material, coming from local or remote infectious sources, within the brain tissue...
. In addition, alterations in the release of neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
s (the chemicals used by brain cells to communicate) can cause secondary injury. Imbalances in some neurotransmitters can lead to excitotoxicity
Excitotoxicity
Excitotoxicity is the pathological process by which nerve cells are damaged and killed by excessive stimulation by neurotransmitters such as glutamate and similar substances. This occurs when receptors for the excitatory neurotransmitter glutamate such as the NMDA receptor and AMPA receptor are...
, damage to brain cells that results from overactivation of biochemical receptors for excitatory neurotransmitters (those that increase the likelihood that a 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...
will fire
Action potential
In physiology, an action potential is a short-lasting event in which the electrical membrane potential of a cell rapidly rises and falls, following a consistent trajectory. Action potentials occur in several types of animal cells, called excitable cells, which include neurons, muscle cells, and...
). Excitotoxicity can cause a variety of negative effects, including damage to cells by free radicals, potentially leading to neurodegeneration
Neurodegeneration
Neurodegeneration is the umbrella term for the progressive loss of structure or function of neurons, including death of neurons. Many neurodegenerative diseases including Parkinson’s, Alzheimer’s, and Huntington’s occur as a result of neurodegenerative processes. As research progresses, many...
. Another factor in secondary injury is loss of cerebral autoregulation, the ability of the brain's blood vessels to regulate cerebral blood flow
Cerebral blood flow
Cerebral blood flow, or CBF, is the blood supply to the brain in a given time. In an adult, CBF is typically 750 millitres per minute or 15% of the cardiac output. This equates to 50 to 54 millilitres of blood per 100 grams of brain tissue per minute. CBF is tightly regulated to meet the brain's...
. Other factors in secondary damage are breakdown of the blood–brain barrier, edema, ischemia and hypoxia. Ischemia is one of the leading causes of secondary brain damage
Brain damage
"Brain damage" or "brain injury" is the destruction or degeneration of brain cells. Brain injuries occur due to a wide range of internal and external factors...
after head trauma. Similar mechanisms are involved in secondary injury after ischemia, trauma, and injuries resulting when a person does not get enough oxygen. After stroke, an ischemic cascade
Ischemic cascade
The ischemic cascade is a series of biochemical reactions that are initiated in the brain and other aerobic tissues after seconds to minutes of ischemia . This is typically secondary to stroke, injury, or cardiac arrest due to heart attack. Most ischemic neurons that die do so due to the...
, a set of 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 takes place.
Prevention
Since primary injury occurs at the moment of trauma and is over so rapidly, little can be done to interfere with it other than prevention of the trauma itself. However, since secondary injury occurs over time, it can be prevented in part by taking measures to prevent complications such as hypoxia. Furthermore, secondary injury presents opportunities for researchers to find drug therapies to limit or prevent the damage. Since a variety of processes occur in secondary injury, any treatments that are developed to halt or mitigate it will need to address more than one of these mechanisms.Thus efforts to reduce disability and death from TBI are thought to be best aimed at secondary injury, because the primary injury is thought to be irreversible.