Editing Diffuse axonal injury (section)

===Histological characteristics===
DAI is characterized by axonal separation, in which the axon is torn at the site of stretch and the part [[Anatomical terms of location#Proximal and distal|distal]] to the tear degrades by a process known as [[Wallerian degeneration]]. While it was once thought that the main cause of axonal separation was tearing due to mechanical forces during the trauma event, it is now understood that axons are not typically torn upon impact; rather, secondary [[biochemical cascade]]s, which occur in response to the [[Primary and secondary brain injury|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.<ref name="Wolf">{{cite journal |vauthors=Wolf JA, Stys PK, Lusardi T, Meaney D, Smith DH |year=2001 |url=http://www.jneurosci.org/cgi/content/abstract/21/6/1923 |title=Traumatic axonal injury induces calcium influx modulated by tetrodotoxin-sensitive sodium channels |journal=Journal of Neuroscience |volume=21 |issue=6 |pages=1923–1930|doi=10.1523/JNEUROSCI.21-06-01923.2001 |pmid=11245677 |pmc=6762603 }}<!--♦♦♦primary♦♦♦--></ref><ref>{{cite journal | pmid = 15371512 | doi=10.1523/JNEUROSCI.1362-04.2004 | volume=24 | title=Vulnerability of central neurons to secondary insults after in vitro mechanical stretch | date=September 2004 | vauthors=Arundine M, Aarts M, Lau A, Tymianski M | journal=Journal of Neuroscience | issue=37 | pages=8106–23| pmc=6729801 }}</ref><ref name="Mouzon2012">{{cite journal | vauthors = Mouzon B, Chaytow H, Crynen G, Bachmeier C, Stewart J, Mullan M, Stewart W, Crawford F | title = Repetitive mild traumatic brain injury in a mouse model produces learning and memory deficits accompanied by histological changes | journal = Journal of Neurotrauma | volume = 29 | issue = 18 | pages = 2761–2173 | date = December 2012 | pmid = 22900595 | doi = 10.1089/neu.2012.2498 | url = http://eprints.gla.ac.uk/72680/7/72680.pdf }}</ref>

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 [[proteolysis|proteolytic]] degradation of the [[cytoskeleton]].<ref name="Iwata">{{cite journal |vauthors=Iwata A, Stys PK, Wolf JA, Chen XH, Taylor AG, Meaney DF, Smith DH |year=2004 |url=http://www.jneurosci.org/cgi/content/abstract/24/19/4605 |title=Traumatic axonal injury induces proteolytic cleavage of the voltage-gated sodium channels modulated by tetrodotoxin and protease inhibitors |journal=The Journal of Neuroscience |volume=24 |issue=19 |pages=4605–4613|doi=10.1523/JNEUROSCI.0515-03.2004 |pmid=15140932 |pmc=6729402 }}<!--♦♦♦primary♦♦♦--></ref> It also opens [[sodium channel]]s in the [[axolemma]], which causes [[voltage-gated calcium channel]]s to open and Ca<sup>2+</sup> to flow into the cell.<ref name="Iwata"/> The intracellular presence of Ca<sup>2+</sup> triggers several different pathways, including activating [[phospholipase]]s and [[proteolytic enzyme]]s damaging [[mitochondria]] and the cytoskeleton, and activating [[secondary messenger]]s, which can lead to separation of the axon and death of the cell.<ref name="Wolf"/>