L15 - Traumatic Brain Injury Flashcards
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
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
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
Animal models of TBI allow for…
the rigourous examination of causal factors and underlying mechanisms involved in TBI
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
true or false
Weight drop can be a small or large, focal or diffuse impact on mouse brain
true
Blast injjury is relevant for…
military inferences
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
what are the advantages of animal models?
- Investigate causal pathophysiological factors/mechanisms - allow tight control of parameters
- Assessment of experimental intervention
- Avoid temporal and other confounding factors
- study chronic condition in months versus years/decades
- cheap!
What are the limitations of animal models?
- interspecies physiological difference
- There is no perfect model
- Haven’t been used effectively
What are inter-species physiological differences relevant for TBI animal research?
different ratios of grey and white matter
metabolic differences
immune system not identical
What is a concussion?
subset of mild TBI
complex pathophysiological process induced by mechanical forces to the brain
true or false
Repetitive mTBI may have cumulative and chronic neurological effects
true
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
A translational research approach to TBi involves..
a bidirectional approach to patients studies and animal models
looking a treatments, biomarkers and effects/mechanisms
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.
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
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
What are 2 non-invasive measures of changes after concussion?
MRI and blood sample
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
cognitive deficits in rats with a mFPI (fluid percussion injury) have cognitive deficits recover by day _
5
no overt brain damage on structural MRI
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
true or false
sodium selenate (PP2A tau dephyophylation catalyst) was beneficial after a single severe TBI in rats
true
What effect does mTBI have on PP2A?
it decreases
therefore mTBI increases phyosphorylated tau
