With of biomechanical forces on the brain are

With the thought of
clinicians underdiagnosing mTBI, it became apparent to researchers that the
effects of biomechanical forces on the brain are to be measured at the
microscale since most cellular network responses are scalable to the complex
functions of a tissue 4, 6. In order to model such effects, forces are to be
applied over an elapsed time of approximately 50 milliseconds to replicate the rapid
and impulsive dynamic loading of the brain onto the skull 3, 4. Pulsed
high-intensity focused ultrasound (pHIFU) has become a preferential gateway
into modelling this scenario because the 50 ms bursts of acoustic shockwaves
that impinge on the surface of a neuronal cell culture can cause them to deform
8. Moreover, in vitro cell models
are relatively quick and efficient to study morphological change, a primary
determinant that initiates a cascade of events leading to excitotoxic cell death,
programmed cell death and post-synaptic receptor modifications 4, 6, 7.

1.1.1
Injuring the brain

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Two categories that are prominent
in understanding the mechanism to induce TBI are contact and inertial forces
4. When an individual strikes their head against a blunt surface, both forces
are observed in a process called impact loading
4. On the other hand, when the head undergoes a series of impulsive motions
in the absence of being physically struck, only inertial loading occurs 4. Given that injuries associated with
contact forces, which involve skull depression or fracture, strongly correlate
with moderate and severe TBI, they are, however, absent in mTBI 1, 4.

            Hypothesizing
that inertial forces motivate mTBI, investigators in the 1940s and 1950s deduced
that peak linear load was linked to a transient increase in peak pressure at a
single location within the brains of their animal subjects 4. Illustrated in
Fig. 1.1, it was also found that another form of inertial loading is rotational acceleration, defined as the
cerebral hemispheres rotating about the midbrain and thalamus in the
anterior-posterior plane 3. Since brain is ultimately composed of water, it
is a relatively soft biologic material that resists anatomic change in the
presence of an applied momentary load 4. Nonetheless, brain is readily susceptible
to deformation under the application of shearing forces, the resultant response
to rotational head loading 4. Shear deformation has become known as the
foremost factor in predicting concussions because in the absence of forcefully
rotating the brain, traumatic unconsciousness is unprocurable 4. With the
midbrain and diencephalic region experiencing the greatest exertion of
rotational forces while consisting of the most alert neurons, interpreting their
electrophysiological and biochemical responses upholds the ability to properly
diagnose the severity of a TBI event 3, 4, 6.