Editing Concussion (section)

==Mechanism==
[[Image:Gatica1.png|thumb|Rotational force is key in a concussion. Punches in [[boxing]] can deliver more rotational force to the head than the typical impact in [[American football]].<ref name=Pellman/>]]

===Forces===
The [[human brain|brain]] is surrounded by [[cerebrospinal fluid]], which protects it from light trauma. More severe impacts, or the forces associated with rapid acceleration, may not be absorbed by this cushion.<ref name="Shaw02">
{{cite journal | vauthors = Shaw NA | title = The neurophysiology of concussion | journal = Progress in Neurobiology | volume = 67 | issue = 4 | pages = 281–344 | date = July 2002 | pmid = 12207973 | doi = 10.1016/S0301-0082(02)00018-7 | s2cid = 46514293 }}</ref> Concussions, and other [[Head injury|head-related injuries]], occur when external [[force]]s acting on the head are transferred to the [[brain]].<ref name="King_2014">{{cite journal | vauthors = King D, Brughelli M, Hume P, Gissane C | title = Assessment, management and knowledge of sport-related concussion: systematic review | journal = Sports Medicine | volume = 44 | issue = 4 | pages = 449–471 | date = April 2014 | pmid = 24403125 | doi = 10.1007/s40279-013-0134-x | s2cid = 207493127 }}</ref> Such [[force]]s can occur when the head is struck by an object or surface (a 'direct impact'), or when the [[torso]] rapidly changes position (i.e. from a [[Checking (ice hockey)#Body checking|body check]]) and force is transmitted to the head (an 'indirect impact').<ref name="King_2014" />

Forces may cause linear, rotational, or angular movement of the brain or a combination of them.<ref name=sivak/> In rotational movement, the head turns around its center of gravity, and in angular movement, it turns on an axis, not through its center of gravity.<ref name=sivak/> The amount of rotational force is thought to be the major component in concussion<ref name=Poirier/> and its severity.<ref name="AndersonT">{{cite journal |vauthors=Anderson T, Heitger M, Macleod AD |year=2006 |url=http://www.vanderveer.org.nz/research/publications/papers/0344.pdf |title=Concussion and mild head injury |journal=[[Practical Neurology]] |volume=6 |pages=342–57 |doi=10.1136/jnnp.2006.106583 |issue=6 |url-status=dead |archive-url=https://web.archive.org/web/20070701212002/http://www.vanderveer.org.nz/research/publications/papers/0344.pdf |archive-date=2007-07-01 |citeseerx=10.1.1.536.9655 |s2cid=73308864 }}</ref> 
As of 2007, studies with athletes have shown that the amount of force and the location of the impact are not necessarily correlated with the severity of the concussion or its symptoms, and have called into question the threshold for concussion previously thought to exist at around 70–75&nbsp;[[G-force|''g'']].<ref name="Guskiewicz">{{cite journal | vauthors = Guskiewicz KM, Mihalik JP, Shankar V, Marshall SW, Crowell DH, Oliaro SM, Ciocca MF, Hooker DN | display-authors = 6 | title = Measurement of head impacts in collegiate football players: relationship between head impact biomechanics and acute clinical outcome after concussion | journal = Neurosurgery | volume = 61 | issue = 6 | pages = 1244–52; discussion 1252–53 | date = December 2007 | pmid = 18162904 | doi = 10.1227/01.neu.0000306103.68635.1a | s2cid = 32598614 }}</ref><ref name="Gever07">{{cite web |url=http://www.medpagetoday.com/Neurology/GeneralNeurology/tb/7625 |title=Any football helmet hit can cause potential concussion |date=December 7, 2007 |author=Gever D |publisher=[[MedPage Today]] |access-date=2008-02-27 |archive-date=2008-05-17 |archive-url=https://web.archive.org/web/20080517055441/http://www.medpagetoday.com/Neurology/GeneralNeurology/tb/7625 |url-status=live }}</ref>

The parts of the brain most affected by rotational forces are the [[midbrain]] and [[diencephalon]].<ref name=Pearce/><ref name=NEJM2007/> It is thought that the forces from the injury disrupt the normal [[cell (biology)|cell]]ular activities in the [[reticular activating system]] located in these areas and that this disruption produces the loss of consciousness often seen in concussion.<ref name=NEJM2007/> Other areas of the brain that may be affected include the upper part of the [[brain stem]], the [[fornix of brain|fornix]], the [[corpus callosum]], the [[temporal lobe]], and the [[frontal lobe]].<ref name="biglered">{{cite journal | vauthors = Bigler ED | title = Neuropsychology and clinical neuroscience of persistent post-concussive syndrome | journal = Journal of the International Neuropsychological Society | volume = 14 | issue = 1 | pages = 1–22 | date = January 2008 | pmid = 18078527 | doi = 10.1017/S135561770808017X | doi-access = free }}</ref> [[Angular acceleration]]s of 4600, 5900, or 7900 [[radian|rad]]/s<sup>2</sup> are estimated to have 25, 50, or 80% risk of mTBI respectively.<ref>{{cite journal | vauthors = Rousseau P, Post A, Hoshizaki TB |title=The effects of impact management materials in ice hockey helmets on head injury criteria |journal=Proceedings of the Institution of Mechanical Engineers, Part P: Journal of Sports Engineering and Technology |issn=1754-3371 |issue=4 |volume=223 |year=2009  |pages=159–65 |doi=10.1243/17543371JSET36 |s2cid=137153670 }}</ref>

===Pathophysiology===
In both animals and humans, mTBI can alter the brain's physiology for hours to years,<ref name="Mouzon2014">{{cite journal | vauthors = Mouzon BC, Bachmeier C, Ferro A, Ojo JO, Crynen G, Acker CM, Davies P, Mullan M, Stewart W, Crawford F | display-authors = 6 | title = Chronic neuropathological and neurobehavioral changes in a repetitive mild traumatic brain injury model | journal = Annals of Neurology | volume = 75 | issue = 2 | pages = 241–254 | date = February 2014 | pmid = 24243523 | doi = 10.1002/ana.24064 | s2cid = 20622669 }}</ref><ref name="Smith2013">{{cite journal | vauthors = Smith DH, Johnson VE, Stewart W | title = Chronic neuropathologies of single and repetitive TBI: substrates of dementia? | journal = Nature Reviews. Neurology | volume = 9 | issue = 4 | pages = 211–221 | date = April 2013 | pmid = 23458973 | pmc = 4513655 | doi = 10.1038/nrneurol.2013.29 }}</ref> setting into motion a variety of [[pathology|pathological]] events.<ref name="pmid11910544">{{cite journal | vauthors = McAllister TW, Sparling MB, Flashman LA, Saykin AJ | title = Neuroimaging findings in mild traumatic brain injury | journal = Journal of Clinical and Experimental Neuropsychology | volume = 23 | issue = 6 | pages = 775–791 | date = December 2001 | pmid = 11910544 | doi = 10.1076/jcen.23.6.775.1026 | s2cid = 20266756 }}</ref> As one example, in animal models, after an initial increase in glucose metabolism, there is a subsequent reduced metabolic state which may persist for up to four weeks after injury.<ref name=Peds2010/> Though these events are thought to interfere with neuronal and brain function, the [[metabolism|metabolic]] processes that follow concussion are reversible in a large majority of affected [[brain cell]]s; however, a few cells may die after the injury.<ref name=Iverson2005/>

Included in the cascade of events unleashed in the brain by concussion is impaired [[neurotransmission]], loss of regulation of [[ion]]s, deregulation of energy use and cellular metabolism, and a reduction in [[cerebral blood flow]].<ref name=Iverson2005/> Excitatory [[neurotransmitter]]s, chemicals such as [[glutamate]] that serve to stimulate nerve cells, are released in excessive amounts.<ref name=Team/> The resulting cellular excitation causes [[action potential|neurons to fire]] excessively.<ref name="GizaHovda">{{cite journal | vauthors = Giza CC, Hovda DA | title = The Neurometabolic Cascade of Concussion | journal = Journal of Athletic Training | volume = 36 | issue = 3 | pages = 228–235 | date = September 2001 | pmid = 12937489 | pmc = 155411 }}</ref> This creates an imbalance of ions such as [[potassium in biology|potassium]] and [[calcium in biology|calcium]] across the cell membranes of neurons (a process like [[excitotoxicity]]).<ref name=Iverson2005/>

At the same time, cerebral blood flow is relatively reduced for unknown reasons,<ref name=Bowen03/> though the reduction in blood flow is not as severe as it is in [[ischemia]].<ref name=Iverson2005/> Thus cells get less glucose than they normally do, which causes an "energy crisis".<ref name=Bowen03/>

Concurrently with these processes, the activity of [[Mitochondrion|mitochondria]] may be reduced, which causes cells to rely on [[anaerobic metabolism]] to produce energy, increasing levels of the byproduct [[lactic acid|lactate]].<ref name=Iverson2005/>

For a period of minutes to days after a concussion, the brain is especially vulnerable to changes in [[intracranial pressure]], blood flow, and [[hypoxia (medical)|anoxia]].<ref name=Bowen03/> According to [[animal study|studies performed on animals]] (which are not always applicable to humans), large numbers of neurons can die during this period in response to slight, normally innocuous changes in blood flow.<ref name=Bowen03/>

Concussion involves [[Focal and diffuse brain injury|diffuse (as opposed to focal) brain injury]], meaning that the dysfunction occurs over a widespread area of the brain rather than in a particular spot.<ref name="Hardman02">
{{cite journal | vauthors = Hardman JM, Manoukian A | title = Pathology of head trauma | journal = Neuroimaging Clinics of North America | volume = 12 | issue = 2 | pages = 175–87, vii | date = May 2002 | pmid = 12391630 | doi = 10.1016/S1052-5149(02)00009-6 }}</ref> It is thought to be a milder type of [[diffuse axonal injury]], because [[axon]]s may be injured to a minor extent due to stretching.<ref name=sivak/> [[Animal experimentation|Animal studies]] in which rodents were concussed have revealed lifelong neuropathological consequences such as ongoing axonal degeneration and [[neuroinflammation]] in subcortical white matter tracts.<ref name="pmid29376093"/> Axonal damage has been found in the brains of concussion patients who died from other causes, but inadequate blood flow to the brain due to other injuries may have contributed.<ref name="Rees03">{{cite journal | vauthors = Rees PM | title = Contemporary issues in mild traumatic brain injury | journal = Archives of Physical Medicine and Rehabilitation | volume = 84 | issue = 12 | pages = 1885–1894 | date = December 2003 | pmid = 14669199 | doi = 10.1016/j.apmr.2003.03.001 }}</ref> Findings from a study of the brains of deceased NFL athletes who received concussions suggest that lasting damage is done by such injuries. This damage, the severity of which increases with the cumulative number of concussions sustained, can lead to a variety of other health issues.<ref name="cnn">{{cite news | work = CNN |url=http://www.cnn.com/2009/HEALTH/01/26/athlete.brains/index.html |title=Dead Athletes Brains Show Damage From Concussions |location=Boston University |publisher=Center for the Study of Traumatic Encephalopathy |access-date=2009-01-28 |date=2009-01-27 |archive-date=2017-01-07 |archive-url=https://web.archive.org/web/20170107181426/http://www.cnn.com/2009/HEALTH/01/26/athlete.brains/index.html |url-status=live }}</ref>

The debate over whether concussion is a functional or structural phenomenon is ongoing.<ref name=McCrory/> Structural damage has been found in the mildly traumatically injured brains of animals, but it is not clear whether these findings would apply to humans.<ref name=Pearce/> Such changes in brain structure could be responsible for certain symptoms such as visual disturbances, but other sets of symptoms, especially those of a psychological nature, are more likely to be caused by reversible pathophysiological changes in cellular function that occur after concussion, such as alterations in neurons' biochemistry.<ref name=AndersonT/> These reversible changes could also explain why dysfunction is frequently temporary.<ref name=McCrory/> A task force of head injury experts called the Concussion In Sport Group met in 2001 and decided that "concussion may result in neuropathological changes but the acute clinical symptoms largely reflect a functional disturbance rather than structural injury."<ref name="aubry">{{cite journal | vauthors = Aubry M, Cantu R, Dvorak J, Graf-Baumann T, Johnston K, Kelly J, Lovell M, McCrory P, Meeuwisse W, Schamasch P | display-authors = 6 | title = Summary and agreement statement of the First International Conference on Concussion in Sport, Vienna 2001. Recommendations for the improvement of safety and health of athletes who may suffer concussive injuries | journal = British Journal of Sports Medicine | volume = 36 | issue = 1 | pages = 6–10 | date = February 2002 | pmid = 11867482 | pmc = 1724447 | doi = 10.1136/bjsm.36.1.6 }}
</ref>

Using animal studies, the pathology of a concussion seems to start with mechanical [[Shearing (physics)|shearing]] and stretching forces disrupting the cell membrane of nerve cells through "mechanoporation".<ref name="Romeu-Mejia_2019">{{cite journal | vauthors = Romeu-Mejia R, Giza CC, Goldman JT | title = Concussion Pathophysiology and Injury Biomechanics | journal = Current Reviews in Musculoskeletal Medicine | volume = 12 | issue = 2 | pages = 105–116 | date = June 2019 | pmid = 30820754 | pmc = 6542913 | doi = 10.1007/s12178-019-09536-8 }}</ref> This results in potassium outflow from within the cell into the extracellular space with the subsequent release of excitatory neurotransmitters including glutamate which leads to enhanced potassium extrusion, in turn resulting in sustained depolarization, impaired nerve activity and potential nerve damage.<ref name="Romeu-Mejia_2019" /> Human studies have failed to identify changes in glutamate concentration immediately post-mTBI, though disruptions have been seen 3 days to 2 weeks post-injury.<ref name="Romeu-Mejia_2019" /> In an effort to restore ion balance, the sodium-potassium ion pumps increase activity, which results in excessive ATP ([[adenosine triphosphate]]) consumption and glucose utilization, quickly depleting glucose stores within the cells.<ref name="Barkhoudarian_2016">{{cite journal | vauthors = Barkhoudarian G, Hovda DA, Giza CC | title = The Molecular Pathophysiology of Concussive Brain Injury - an Update | journal = Physical Medicine and Rehabilitation Clinics of North America | volume = 27 | issue = 2 | pages = 373–393 | date = May 2016 | pmid = 27154851 | doi = 10.1016/j.pmr.2016.01.003 }}</ref> Simultaneously, inefficient [[oxidative metabolism]] leads to [[anaerobic metabolism]] of glucose and increased lactate accumulation.<ref name="Barkhoudarian_2016" /> There is a resultant local [[acidosis]] in the brain and increased cell [[membrane permeability]], leading to local swelling.<ref name="Barkhoudarian_2016" /> After this increase in glucose metabolism, there is a subsequent lower metabolic state which may persist for up to 4 weeks after injury. A completely separate pathway involves a large amount of calcium accumulating in cells, which may impair oxidative metabolism and begin further biochemical pathways that result in cell death. Again, both of these main pathways have been established from animal studies and the extent to which they apply to humans is still somewhat unclear.<ref name=Peds2010/>