Animal models of TBI

Question 1

List long term effects of TBI

Answer 1

• Increase mortality in head injury

- Alzheimer’s increased risk, possibly due to inflammation

Question 2

Why do clinical trials fail?

Answer 2

• Rushing to conduct the trial without sufficient animal data (eg. CRASH study)
• Low number of participants, multicentre trials are better
• Patient selection (confounding factors, sex, one severity group?)
• Endpoint (GCS, impairments, survival)

Question 3

List important factors in animal models

Answer 3

• A signal model can’t reproduce TBI
• But animal models are necessary to identify mechanisms and test therapies
• Face validity, Construct validity, etiological validity, predictive validity and reliability

Question 4

List animal models

Answer 4

• Drosophilia - a fruit fly. Cheap, ethical, fast life cycle, easy genetic modifications. However, low biomechanics and reproducability, limited behaviour tests, no skull.
• Zebrafish - same advantages, with behavioural effects observable, however, they have a different metabolism

Question 5

How are TBI models classified?

Answer 5

• Mechanical force (amplitude, duration, velocity, acceleration). May be direct or indirect
• Focal vs diffuse injury patterns

Question 6

Describe the controlled cortical impact model

Answer 6

• Based on pioneering work in spinal cord injury
• Adapted for brain injury
• Fast compression of the dura and cortex
• Results in a focal contusion in cortical tissue and some of the underlying structures
• Pros: highly reproducible, full control of all biomechanical parameters, severity is mainly governed by impact depth. There is species scalability (rodents, ferret, pig, non-human primate). Age effects. Low mortality
• Cons: complex instruments prone to wear, craniotomy required, pronounce tissue loss possible.
• Evolved to closed head injury/ repeated mild injury to model chronic TBI, using repeated head injury in awake animals

Question 7

Describe fluid precussion

Answer 7

• Fluid wave impacts the brain
• Severity is governed by pressure
• Pros: reprodycible, single severity methods, modelling of oxonal and diffuse injury
• Cons: craniotomy needed, higher mortality, brainstem and ventricular involvement

Question 8

Describe weight drop models

Answer 8

• Developed directly for rodents
• Free falling guided weights hit the exposed dura
• Results in focal, diffuse or mixed injuries
• Pros: easy set up
• Cons: craniotomy necessary, primarily in rodents, higher mortality, less reproducibility

Question 9

Describe the penetrating ballistic-like model

Answer 9

• Projectile penetrating into the bain, eg. air rifle pellets and probes
• Generates a shockwave and a temporary cavity which is larger than the projectile
• Pros: similar biomechanics to penetrating TBI
• Cons: craniotomy, clinically less often seen, reproducibility

Question 10

Describe blast injury model

Answer 10

• Blast exposure is the signature wound of the modern battlefield
• Over pressure followed by negative pressure
• Shock tube or open field explosions
• Diffuse axonal injury, diffuse oedema, significant peripheral effects when the body is exposed
• Pros: similar biomechanics to human blast TBI
• COn: only seen in military setting, difficulty with reproducibility