Primary and secondary brain 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 (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.cite book|editor = Valadka AB, Andrews BT |author = Scalea TM| chapter= Does it matter how head injured patients are resuscitated? |date = 2005 |title= Neurotrauma: Evidence-Based Answers To Common Questions |publisher = Thieme | isbn= 3131307811 |pages= 3–4 ] Secondary injury, which is not caused by mechanical damage, can result from the primary injury or be independent of it.cite book |author=Gennarelli GA, Graham DI |chapter=Neuropathology |editor= Silver JM, McAllister TW, Yudofsky SC |title=Textbook Of Traumatic Brain Injury |publisher=American Psychiatric Association |location=Washington, DC |year=2005 |pages= 27–33| isbn=1-58562-105-6 |oclc= |doi= |accessdate=2008-06-10 |url =,M1] 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.cite book |author=Porth, Carol |title=Essentials of Pahtophysiology: Concepts of Altered Health States |publisher=Lippincott Williams & Wilkins |location=Hagerstown, MD |year=2007 |pages=838 |isbn=0-7817-7087-4 |oclc= |doi= |accessdate=2008-07-03 |url=] Primary injury occurs at the moment of trauma and includes contusion, damage to blood vessels, and axonal shearing, in which the axons of neurons are stretched and torn. The blood brain barrier and meninges may be damaged in the primary injury, and neurons may die.cite journal |author=Pitkänen A, McIntosh TK |title=Animal models of post-traumatic epilepsy |journal=Journal of Neurotrauma |volume=23 |issue=2 |pages=241–261 |year=2006 |pmid=16503807 |doi=10.1089/neu.2006.23.241] Cells are killed in a nonspecific manner in primary injury.cite book| author = LaPlaca MC, Simon CM, Prado GR, Cullen DR |chapter = CNS injury biomechanics and experimental models |pages= 13–19 |url =,M1 |accessdate=2008-06-10 |title=Neurotrauma: New Insights Into Pathology and Treatment
editor= Weber JT| isbn=0444530177
] 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, myelinated 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 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.cite journal |author=Sullivan PG, Rabchevsky AG, Hicks RR, Gibson TR, Fletcher-Turner A, Scheff SW |title=Dose-response curve and optimal dosing regimen of cyclosporin A after traumatic brain injury in rats |journal=Neuroscience |volume=101 |issue=2 |pages=289–95 |year=2000 |pmid=11074152 |doi= |url= ] 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.cite journal |author=Sauaia A, Moore FA, Moore EE, "et al" |title=Epidemiology of trauma deaths: A reassessment |journal=J Trauma |volume=38 |issue=2 |pages=185–93 |year=1995 |month=February |pmid=7869433 |doi= |url= ] In addition, rather than improving after being hospitalized as most patients with other types of injuries do, about 40% of people with TBI deteriorate.cite journal |author=Narayan RK, Michel ME, Ansell B, "et al" |title=Clinical trials in head injury |journal=J. Neurotrauma |volume=19 |issue=5 |pages=503–57 |year=2002 |month=May |pmid=12042091 |pmc=1462953 |doi=10.1089/089771502753754037 |url=] 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 hemorrhage, stroke, and traumatic brain injury and involves metabolic cascades.

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),cite book |author=Andrews BT |chapter= Head injury management |editor=Andrews BT |title=Intensive Care in Neurosurgery |publisher=Thieme Medical Publishers |location=New York |year=2003 |pages=125 |isbn=1-58890-125-4 |oclc= |doi= |accessdate=2008-06-08 |url =,M1] meningitis, and brain abscess. In addition, alterations in the release of neurotransmitters (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.cite journal |author=Garga N, Lowenstein DH |title=Posttraumatic epilepsy: A major problem in desperate need of major advances |journal=Epilepsy Curr |volume=6 |issue=1 |pages=1-5 |year=2006 |pmid=16477313 |doi=10.1111/j.1535-7511.2005.00083.x |url=] Ischemia is one of the leading causes of secondary brain damage after head trauma.cite book |author=Granacher RP |title=Traumatic Brain Injury: Methods for Clinical & Forensic Neuropsychiatric Assessment, Second Edition |publisher=CRC |location=Boca Raton |year=2007 |pages= 26–32|isbn=0-8493-8138-X |oclc= |doi= |accessdate=2008-07-06 |url=,M1] 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 cascades takes place.


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.cite book |author=Marion DW |chapter= Pathophysiology and treatment of intracranial hypertention |editor=Andrews BT |title=Intensive Care in Neurosurgery |publisher=Thieme Medical Publishers |location=New York |year=2003 |pages=52–53 |isbn=1-58890-125-4 |oclc= |doi= |accessdate=2008-06-08 |url =,M1]

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.cite journal |author=Armin SS, Colohan AR, Zhang JH |title=Traumatic subarachnoid hemorrhage: Our current understanding and its evolution over the past half century |journal=Neurol. Res. |volume=28 |issue=4 |pages=445–52 |year=2006 |month=June |pmid=16759448 |doi=10.1179/016164106X115053]


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