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.[24] It also opens sodium channels in the axolemma, which causes voltage-gated calcium channels to open and Ca2+ to flow into the cell.[24] The intracellular presence of Ca2+ triggers several different pathways, including activating phospholipases 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.[2]