In diffuse axonal injury, most damage unfolds hours to days after impact
It was long assumed that brain fibres snap at the moment of a violent jolt. Researchers now think most axons in diffuse axonal injury are not torn on impact at all. Instead, chemical chain reactions set off by stretching break them down over the following hours and days.
Diffuse axonal injury, or DAI, scatters small lesions across wide areas of the brain's white matter tracts and grey matter. It is one of the most common and serious forms of traumatic brain injury, appearing in roughly half of severe head trauma cases, and a leading reason people remain unconscious or in a persistent vegetative state. Over 90 percent of patients with severe DAI never wake, and survivors are often left seriously impaired. Concussion, by contrast, may be a gentler form of the very same process.
The cause is shearing when the head speeds up or slows down suddenly, most often in vehicle crashes, but also in falls and assaults. Lesions, usually about 1 to 15 mm across, cluster in a recognisable pattern, favouring the corpus callosum, the brain stem and both cerebral hemispheres, with the frontal and temporal lobes the most vulnerable. Regions like the thalamus and basal ganglia may be at extra risk because their density differs from surrounding tissue.
Axons are normally springy, yet a rapid stretch makes them brittle, and their internal scaffolding, the cytoskeleton, can crack. The stretch also opens sodium channels in the cell membrane, which in turn lets calcium pour in. Calcium activates enzymes that damage mitochondria and the cytoskeleton and triggers signalling that can end with the axon separating and the neuron dying. Researchers still do not fully understand these secondary processes.
Transport of materials along the axon carries on up to the break and then stalls, so cargo piles up and the fibre swells. Eventually the swelling can split the axon, which recoils towards the cell body and forms a knob called a retraction ball, the telltale sign under the microscope. The severed far end then decays through Wallerian degeneration. Studies have also tied the damage to twisted microtubules and deposits of tau and amyloid precursor protein.
Source: Diffuse axonal injury
