Primary versus Secondary Injury

Dr Nicole Bye:
We're now going to describe the injury that is occurring within the brain itself. Specifically,
we'll discuss how brain injury results from both immediate and ongoing mechanisms, which
are called primary and secondary injury, respectively, and then we'll describe the two main
types of primary TBI: focal, and diffuse.

Primary injury is the initial damage that occurs at the time of the head injury. This is damage
results directly from the mechanical forces affecting the brain tissue, such as the force of a
blow to the head, or acceleration and deceleration forces.

Following the primary injury, there's an ongoing period of secondary damage. This starts
within seconds after injury and can continue for many months. Secondary injury includes a
series of steps of cellular, chemical, tissue, and blood vessel changes in the brain that
contribute to further ongoing destruction of the brain tissue. The types and extent of
secondary insults that arise depend on the type and severity of the primary injury. We'll talk
in more detail about secondary injury mechanisms in later modules.

The primary brain injury occurring as a direct result of head injury is classified as two
different types: focal and diffuse. Focal injury is tissue damage that's localised to a particular
spot within the brain, often called a contusion or lesion - like a bruising of the brain. Diffuse
injury, on the other hand, is spread more globally throughout the brain and predominantly
affects the long axons that comprise the white matter connecting the different brain
regions. Focal lesions are easy to identify with standard imaging techniques and may even
be surgically removed to aid in recovery, but diffuse brain injury is often very difficult to
detect. While we often describe primary brain injury as predominantly focal or diffuse, it's
very important to understand that these two injury types very often coexist, especially in
severely injured patients. So, we'll now describe these two types of brain injury in more
detail.

Focal traumatic brain injury is produced by collision forces of the brain impacting on the
skull and resulting in compression of the tissue underneath the cranium. The location and
severity of the impact ultimately determine the extent of brain damage and neurological
dysfunction. These collision forces can lead to different types of focal lesions, including
contusions and lacerations. The force of collision can also tear blood vessels causing
bleeding into the brain which then also contributes to focal injury.

In this animation of a closed head injury that we saw earlier, we can see that focal brain
damage is produced by collision forces of the brain impacting on the skull and resulting in
compression of the tissue at the site of impact, and also at the opposite side. This results in

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two contusion injuries often called coup and contrecoup. A contusion is the result of the
direct damage to the neurons, glial cells, and blood vessels exposed to the compression
forces.

Lacerations are another type of focal brain injury that involve tearing of the brain tissue as
the brain rotates across the rough ridges inside the skull. Lacerations are also caused during
open head injury by an object penetrating the brain.

This primary focal injury to the brain initiates numerous secondary processes such as
swelling - which we call oedema, and also the release of toxic molecules from damaged
cells. These events then trigger the ongoing degeneration and death of neurons in the
affected area, which we call secondary brain injury.

In addition to contusions and lacerations a third type of focal injury following TBI is when
bleeding (or haemorrhaging) occurs within the brain, or between the brain and the skull,
resulting in an accumulation of blood called an intracranial hematoma. There are multiple
types of hematomas that form within the head based on the region in which the blood
vessels have ruptured. Importantly hematomas can cause contusion injuries by compressing
the brain, causing a lack of oxygen and swelling in the affected tissue.

The second type of primary brain injury is diffuse brain injury. Diffuse brain injury is caused
by those rotational and linear acceleration/deceleration forces experienced by the brain
during violent motions of the head. Diffuse brain injury entails widely distributed damage to
axons - those long fragile projections connecting the different brain regions, and this
damage is called diffuse axonal injury. A second pathology of diffuse brain injury is the
damage to very fine blood vessels causing microbleeds throughout the brain.

The damage to the axons, or diffuse axonal injury, is caused by shearing forces that are
generated within the brain tissue when certain segments of the brain move at a faster rate
than others. For example, as illustrated here, the grey matter of the cortex is composed of
the neuronal cell bodies and is a different density than the white matter, which is composed
of the long thin axonal projections. Following a sudden violent movement of the head this
difference in tissue density causes shearing forces at the grey and white matter interface
which directly damages the axons along a plane of cleavage. If the forces experienced by the
brain are even more severe, blood vessels in this region may also be injured causing
bleeding into the brain.

Areas of the brain most susceptible to traumatic axonal injury are the grey and white matter
interface, as well as the long white matter projections of the corpus callosum and the
brainstem.

An important secondary injury event that occurs following diffuse brain injury is global
oedema, or swelling throughout the whole brain. This leads to increased intracranial
pressure, which can cause further damage to neurons.

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In this video we've learned about the differences between the two types of primary injury
that occur at the time of trauma: focal and diffuse. We've also introduced the concept of
secondary injury mechanisms that contribute to the ongoing damage in the brain. An
interesting distinction between primary and secondary injuries is that the primary injury -
whether focal or diffuse - cannot be altered once it has occurred, however its severity can
be controlled by preventative and safety measures, such as wearing helmets or seat belts.
The ongoing mechanisms driving secondary injuries on the other hand are potentially
treatable, and considerable research effort is being made to investigate these processes as
possible targets for therapeutic intervention and treatment of traumatic brain injury.

These concepts of primary and secondary injury will be discussed in more detail in future
modules focusing on specific categories of brain injury, including concussion and moderate
to severe TBI.

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