Traumatic brain injury (TBI) is the most frequent neurological disorder worldwide. Over 1.7 Million individuals suffer a TBI each year with an incidence of 235–556/100,000. In severe TBI cases, fatality rates mount up to 40%, and in survival disability rate, it is as high as 55–77%, leading to reduce in the quality of life. TBI is caused by head trauma, including the more typical closed head injury, in which rapid acceleration or deceleration induces shearing to the cerebral tissue and produces other forces in the brain and impacts against the frontal and temporal fossae of the skull. TBI is associated with the later onset of neurodegenerative disorders. One of the most common across all ...view middle of the document...
A dynamic stretch injury in vitro model has been used to show the evidence of primary mechanical damage to axons. Within seconds of dynamic axonal stretch, the axons lose their elasticity and they are exposed to cytoskeleton disruption to become undulated. Undulated axons are common features of TBI; therefore, it suggested that the primary cytoskeletal failure is due to mechanical trauma.
Recently, in vitro models, studies have shown that post-traumatic axonal undulation is followed by primary breaking of axonal microtubules. Misalignment and twisting of microtubules along the injured axons at multiple sites can impede the elasticity of axons. This interrupts axonal transport and induces swelling and axonal degeneration.
However, the question about how these differences are related to the structural variation between these populations of neurons is still unknown.
B. Secondary Chemical Cascades
During TBI, all the axons in the white matter undergo dynamic deformation, but a small percentage even in severe TBI goes to be well due to the transportation interruption. The remaining axons may suffer pathophysiological changes, which leads to axonal dysfunction. One of these changes is ionic balance. Injured axons have elevation of intra-axonal Ca2+ levels. Maxwell and others found indirect evidence of post-traumatic calcium influx into axons via changes in calcium-ATPase activity after optic nerve stretch injury (Johnson et al., 2013, p.38).
Calcium influx rises immediately following trauma. In both vitro and vivo models, there is an increase in Ca2+ activates Calpine, which leads to proteolysis of both target and non-target proteins and irreversible tissue damage. Active Calpin breaks down cytoskeleton, microtubules, neurofilament and ion channels such as sodium channels under axonal stretch injury. Damage of sodium ion channel leads to influx of Na+, which, in turn, leads to depolarization and influx more calcium.
C. DIA genesis / Models
Experimental animals’ models have been used to confirm that the rotational acceleration of the brain is the responsible mechanical force of DAI, resulting from unrestricted movement of the head inducing dynamic shear and compressive strains within the tissue. Different models have been designed to stimulate the dynamics of DAI and study the causes that lead to DIA in human brain.
Instant Rotational Injury Model
Instant Rotational Injury Model of DAI was developed in 1980s. They used nonhuman primates, due to their large size of brain, with extensive white matter similar to human brain. This model uses a pneumatic shock tester in order to generate a non-impact and controlled single rotation. The...