<P> Lesions typically exist in the white matter of brains injured by DAI; these lesions vary in size from about 1--15 mm and are distributed in a characteristic way . DAI most commonly affects white matter in areas including the brain stem, the corpus callosum, and the cerebral hemispheres . </P> <P> The lobes of the brain most likely to be injured are the frontal and temporal lobes . Other common locations for DAI include the white matter in the cerebral cortex, the superior cerebral peduncles, basal ganglia, thalamus, and deep hemispheric nuclei . These areas may be more easily damaged because of the difference in density between them and the rest of the brain . </P> <P> DAI is characterized by axonal separation, in which the axon is torn at the site of stretch and the part distal to the tear degrades . While it was once thought that the main cause of axonal separation was tearing due to mechanical forces during the trauma, it is now understood that axons are not typically torn upon impact; rather, secondary biochemical cascades, which occur in response to the 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 . </P> <P> 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 . It also opens sodium channels in the axolemma, which causes voltage - gated calcium channels to open and Ca to flow into the cell . The intracellular presence of Ca unleashes 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 . </P>

When do symptoms of axon damage show up