The document discusses traumatic brain injury (TBI) research using animal models. It describes different TBI models including fluid percussion injury, controlled cortical impact, acceleration injury, and blast injury. Each model has advantages and limitations in mimicking different types of human TBI. The document also summarizes a recent study where deceased pig brains were connected to a system called BrainEx that restarted some cellular functions, raising ethical concerns. While animal models are necessary for brain research, they have limitations due to anatomical differences between species and raise issues regarding the definition of death and harm to animals.

1. Brain
Damage/Abnormal
Behavior/Stereotypic
Behavior
Kaylee Breedlove

2. A “Risky” Operation

3. Traumatic Brain Injury (TBI): Key Concepts/Terminology
- Traumatic Brain Injury (TBI): damage to the brain
resulting from an external mechanical force, such as
that caused by rapid acceleration or deceleration, blast
waves, crush, an impact, or penetration by a projectile
- Can lead to temporary or permanent impairment
of cognitive, physical, and psychosocial functions
★ TBI is the leading cause of death &
disability for people under the age of 45
- *Diffuse Axonal Injury (DAI): a brain injury in which
scattered lesions in both white & gray matter occur
over a widespread area.

4. Traumatic Brain Injury (TBI): Key Concepts/Terminology (contd.)
● Gray Matter: dark areas of brain/spinal
cord; consists of nerve cell bodies and
dendrites
○ Areas of the brain that are dense
with gray matter are heavily involved
with motor & sensory activity
● White Matter: light-colored areas of the
brain/spinal cord that consists mainly of
myelinated axons which function as
connections between cells
● Gyri & Sulci: folds & indentions which
give the brain its wrinkled appearance

5. Animal Brain Anatomy: Humans vs. Animals
● Large vs. small animal brain structure:
○ Rodents: have lissencephalic brains
■ Bony skull with less gyri/sulci → less protection
for the brain upon impact
○ Humans: have gyrencephalic brains
■ More gyri/sulci → more surface area to cover
the brain and provide protection (to an extent)
○ Large animal brain structure is more similar to
human brain structure
■ Example → Pig brains are often used to gain
knowledge about pediatric TBI in humans
● Differences in densities of gray & white matter across
species

6. TBI Animal Research Models
- Most common animal used for brain experimentation = rodents
- However, research is not limited to rodents!
- Significant variation in the species that are selected for brain research
- 4 models for TBI research on non-human animals:
1. Fluid Percussion Injury (FPI)
2. Controlled Cortical Impact (CCI) Injury
3. Acceleration Injury
4. Blast Injury
?: How do experimenters decide which injury model would be most
appropriate to use for their research? Answer: Injury model selection is largely
based on its uniqueness, the extent of data reproducibility, & relevance to
research on TBI in humans

7. 1. ) Fluid Percussion Injury Model (FPI)
● A fluid pulse is driven rapidly into
epidural space, targeting the intact dura
● Used to examine non-fracture/brief
impact TBI injuries
● PRO: pressure exerted by the pendulum
onto the cranium can be manipulated by
the experimenter
Strength (of impact) + location = severity of injury
● CONS:
○ Craniotomy = necessary
○ Mortality rate of subjects is very
high

8. 2.) Controlled Cortical Impact Injury Model (CCI)
● An air (or electromagnetic) driven
piston is used to penetrate the brain
● PROS:
○ Allows experimenter to highly
regulate various factors of the
focal impact (e.g. time, velocity,
depth)
○ Damage can be inflicted onto
multiple areas of the brain
○ Minimal risk for rebound injury =
increased reliability
● CON: craniotomy = necessary

9. 3.) Acceleration (or Weight-Drop) Injury Model
● A free weight is dropped onto the exposed dura
● PROS:
● Allows experimenter to manipulate subject’s
cranium in a way which mimics the impact of a head
rotational injury
■ Examples of human head rotational injuries
include: falls, collisions, and blunt impacts,
**Contact sports!
● Inclusion of rotational component → allows us to
examine the biomechanical forces that produce loss
of consciousness and diffuse axonal injury (DAI)
■ BOTH injuries = common TBI’s experienced by
humans
● Convenience: Simple to perform, CHEAP ($) &
craniotomy = NOT necessary!
● CON: High variability in severity of injury

10. 4.) Blast Injury Model
● A blast wave is detonated in
order to induce injury to the brain
● Even MILD blast injury can result
in deficits associated with spatial
memory, motor coordination &
problems with social recognition
CON: significant variability in
experimentation → decrease in
reproducibility
*FUN FACT*
Blast injuries are commonly experienced
by military personnel → Blast model
research is helpful for determining
treatment for blast-induced TBI’s, as well
as generating new treatment methods
for these individuals

11. BrainEx Research Study
- Experiment was conducted by
researchers at Yale School of
Medicine
- 32 pig brains were used…
post-mortem
- Acquired from the U.S. Department of
Agriculture’s slaughterhouse
- Pigs had been deceased for ~4 hours
- Deceased pig brains were
connected to a complex system
called BrainEx
- BrainEx mimics blood flow within the
brain which allows the perfusion
system to take on the functions that are
normally regulated by the organ

12. Well… What Happened to Yale’s “Zombie” Pigs?
● BrainEx → RESTORED blood circulation & oxygen flow to the deceased
pig brains!
○ Some of the pig brains stayed “alive” for up to 36 hours
● However, the researchers did NOT restore consciousness to the pig
brains in any way
With the help of BrainEx, the pig brains were able to begin the process of
restoring normal functions...
❏ The brain cells responded to drugs
❏ Immune system functioning began to regenerate
❏ Brain cells began consuming/metabolizing sugars
❏ Neuron’s could maintain an electrical signal

13. BrainEx: The Aftermath...
What can we learn from the BrainEx experiment?
➢ The power of technology is in the hands of our research
professionals
○ Technological advancements in animal
experimentation will allow researchers to expand
our understanding about the human brain
➢ Animal brain experimentation opens up new doors for
the potential development of new treatment methods
associated with brain-related impairments, diseases, etc.
➢ However, BrainEx & the use of other animal models
continues to raise important ethical questions...
○ E.g. What happens when brain death becomes
readily reversible?

14. Limitations of Current Animal Research Models
➔ Objective differences between animals and humans
◆ Structural variation within the brain between species
● Large animal brains → Generally, are more structurally similar to the human
brain
◆ Sex differences
◆ Differences in muscle mass/structural anatomy
◆ Differences in cerebral blood supply across species
➔ Small-scale differences in experimentation
◆ Variability in craniotomy positioning
● Rotational injury = difficult to model using animals
● In humans: head rotation = critical factor related to loss of consciousness
➔ $$$ → Many experiments are expensive to fund
◆ Rat models = low-cost option as compared to large animal experimentation
◆ HOWEVER, Rodent brains are quite structurally distinct from the human brain

15. Animal Brain Experimentation: Ethical Concerns
● Raises questions about how we should define “death”
○ Inability to medically define “death” could potentially cause massive
disruption/corruption in the way medical professionals handle organ donation
○ Could dramatically decrease the pool of eligible organ donors
● Concerns about the intensity of distress/harm being inflicted onto animal subjects
★ How would one make ethical decisions/judgements about
experimentation involving a brain that is considered to be “active” even
though the animal itself is long since deceased?
★ How could animal injury models be adapted/reconstructed in order to
conduct ethically appropriate human brain experimentation?

16. Conclusions about TBI Animal Research:
TBI research on non-human animals is…
❏ Necessary in order to develop future
advancements in human brain research,
experimentation, technology, and
treatment
❏ Controversial/Ethically Concerning
❏ Highly influenced by technological
advancements

17. Questions?

18. References
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Farahany, N. A., Greely, H. T., & Giattino, C. M. (2019). Part-revived pig brains raise slew of ethical quandaries. Nature, 568(7752),
299–302. https://doi.org/10.1038/d41586-019-01168-9
Vink, R. (2017). Large animal models of traumatic brain injury. Journal of Neuroscience Research, 96(4), 527–535.
https://doi.org/10.1002/jnr.24079
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https://doi.org/10.1038/nrn3407
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10.1016/j.brainres.2009.06.067