L15 - Traumatic Brain Injury Flashcards Preview

Seminars in Translational Medicine > L15 - Traumatic Brain Injury > Flashcards

Flashcards in L15 - Traumatic Brain Injury Deck (27):
1

Why is TBI a problem?

common cause of death and morbidity worldwide

Increased incidence of other neurodegenerative conditions

currently no effective pharmacological treatment

poor understanding of complex pathophysiology

2

What happens in TBI?

in particular name some primary and secondary in jury mechanisms

Primary Injury mechanisms (ireversible):
-mechanical tissue disruption
-necrotic cell death
-axonal shearing
-BBB damage

Secondary Injuiry mechanisms
- Neuroinflammation
- H-Tau
-ROS
etc...

Main point: very complex and things aren't independent of each other

3

What kind of patient studies can we do and are they rigourous?

neurophysiological/psychologuical tests

Neuroimagine

Microdialysis/CSF

Post-mortem

Due to technical, methodological, ethical , financial and temporal limitations we cannot rigourously study TBI solely in patients

4

Animal models of TBI allow for...

the rigourous examination of causal factors and underlying mechanisms involved in TBI

5

Describe the Fluid Percussion injury?

controlled cortical impact: gives a focal impact and diffuse injury to mouse

fluid pulse passed onto brain

pendulum can be adjusted

6

true or false

Weight drop can be a small or large, focal or diffuse impact on mouse brain

true

7

Blast injjury is relevant for...

military inferences

8

What are the scientific methods of analysing animal models?

Everything as for patients and more

extensive neuroimaging

behaviour

physiology

molecular

whenever you want with advanced techniques

9

what are the advantages of animal models?

1. Investigate causal pathophysiological factors/mechanisms - allow tight control of parameters

2. Assessment of experimental intervention

3. Avoid temporal and other confounding factors

4. study chronic condition in months versus years/decades

5. cheap!

10

What are the limitations of animal models?

1. interspecies physiological difference

2. There is no perfect model

3. Haven't been used effectively

11

What are inter-species physiological differences relevant for TBI animal research?

different ratios of grey and white matter

metabolic differences

immune system not identical

12

What is a concussion?

subset of mild TBI

complex pathophysiological process induced by mechanical forces to the brain

13

true or false

Repetitive mTBI may have cumulative and chronic neurological effects

true

14

True or false

concussion increases incidence of numerous neurodegenerative diseases
- Alzheimers
- MND
- Chronic Traumatic Encephalopathy (neurodegenerative condition with severe cognitive, emotional and motor symptoms)

true

plus risk factor of depression

15

A translational research approach to TBi involves..

a bidirectional approach to patients studies and animal models

looking a treatments, biomarkers and effects/mechanisms

16

For NRL players long term studies have indentified...

neurophycholigcal outcomes- memory, recall

but these aren't resulting in a deficit or abnormality

so you cannot conlcude that mild brain traumas CAUSE long term neurological deficits and neurodegeneration from it.

17

when you give repetitive injuries you still see significant effect with one but the conditions are ____ with multiple injuries

when you give repetitive injuries you still see significant effect with one but the conditions are worse with multiple injuries

18

true or false

repetitive mTBIs may have long-term neuro effects and may be dure to 2nd mTBI during vulnerable period which means it is important to DIAGNOSE WITH OBJECTIVE BIOMARKERS

true

19

What are 2 non-invasive measures of changes after concussion?

MRI and blood sample

20

Name some behaviour, MRI and blood biomarkers in mice

behaviour
- water maze = cognitive
- Elevated plus = anxiety
- forced swim = depession

MRI
- weighted MRI= structural damage

Blood
- cell death = NSE
- axonla injury = NF-H

21

cognitive deficits in rats with a mFPI (fluid percussion injury) have cognitive deficits recover by day _

5

no overt brain damage on structural MRI

22

In rat studies of mTBI following mFPI what were the study findings?

MRI, blood and behaviour changes post mFBI
- consistnet with human studies

2nd injury after behavioural recovery = exacerbated outcomes

patient studies began in 2015 but remaining hurdles include feasibility, biological relevance

23

true or false

sodium selenate (PP2A tau dephyophylation catalyst) was beneficial after a single severe TBI in rats

true

24

What effect does mTBI have on PP2A?

it decreases

therefore mTBI increases phyosphorylated tau

25

By selenate post TBI increasing PP2A and reducing phyosphorylated tau what is effected?

atrophy, behavioural impairments and axonal injury is reduced

26

Does selenate reprsent a translatable treatment approach?

YES!

but more complimentary approaches are neccessary

27

IN EXAM

What is the awake, closed head model?

A new neuro-model that addresses the confounding craniotomy and anesthetic factors that are present in other mTBI models

Rats are awake when they have their injury