With the thought ofclinicians underdiagnosing mTBI, it became apparent to researchers that theeffects of biomechanical forces on the brain are to be measured at themicroscale since most cellular network responses are scalable to the complexfunctions of a tissue 4, 6. In order to model such effects, forces are to beapplied over an elapsed time of approximately 50 milliseconds to replicate the rapidand impulsive dynamic loading of the brain onto the skull 3, 4. Pulsedhigh-intensity focused ultrasound (pHIFU) has become a preferential gatewayinto modelling this scenario because the 50 ms bursts of acoustic shockwavesthat impinge on the surface of a neuronal cell culture can cause them to deform8. Moreover, in vitro cell modelsare relatively quick and efficient to study morphological change, a primarydeterminant that initiates a cascade of events leading to excitotoxic cell death,programmed cell death and post-synaptic receptor modifications 4, 6, 7.1.
1.1Injuring the brainTwo categories that are prominentin understanding the mechanism to induce TBI are contact and inertial forces4. When an individual strikes their head against a blunt surface, both forcesare observed in a process called impact loading4. On the other hand, when the head undergoes a series of impulsive motionsin the absence of being physically struck, only inertial loading occurs 4.
Given that injuries associated withcontact forces, which involve skull depression or fracture, strongly correlatewith moderate and severe TBI, they are, however, absent in mTBI 1, 4. Hypothesizingthat inertial forces motivate mTBI, investigators in the 1940s and 1950s deducedthat peak linear load was linked to a transient increase in peak pressure at asingle location within the brains of their animal subjects 4. Illustrated inFig. 1.1, it was also found that another form of inertial loading is rotational acceleration, defined as thecerebral hemispheres rotating about the midbrain and thalamus in theanterior-posterior plane 3.
Since brain is ultimately composed of water, itis a relatively soft biologic material that resists anatomic change in thepresence of an applied momentary load 4. Nonetheless, brain is readily susceptibleto deformation under the application of shearing forces, the resultant responseto rotational head loading 4. Shear deformation has become known as theforemost factor in predicting concussions because in the absence of forcefullyrotating the brain, traumatic unconsciousness is unprocurable 4. With themidbrain and diencephalic region experiencing the greatest exertion ofrotational forces while consisting of the most alert neurons, interpreting theirelectrophysiological and biochemical responses upholds the ability to properlydiagnose the severity of a TBI event 3, 4, 6.