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TMS exam > 7 - diagnosis and treatment of TBI > Flashcards

7 - diagnosis and treatment of TBI Flashcards

1
Q

treatment for the neurotoxic cascade

A

there is no drug treatment

however cooling slows processes down

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2
Q

why is cooling an effective treatment for neurotoxicity

A

blood is temperature sensitive
cooling slows processes down
e.g. lack of O2 and glutamate transmission
able to restore some function

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3
Q

use of x-ray to diagnose TBI

A

only useful to show bone fractures in the skull

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4
Q

use of CT-scan to diagnose TBI

A

shows bleeding within the skull area

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5
Q

use of MRI scan

A

shows build up of fluid

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6
Q

imaging methods for TBI

A 
x-ray
CT scan
MRI
EEG
PET
DTI
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7
Q

which imaging method shows whether there is damage within the brain

A

DTI

Diffusion Tensor Imaging

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8
Q

features of DTI

A
  • separates axon tracks
  • able to show location of injury and what part of the brain it will affect (where the tracks are headed in relation to the functional areas of the brain)
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9
Q

why is it important to see axons in imaging when diagnosing TBI

A

(axons are shown to be missing in TBI patients)

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10
Q

disadvantage of DTI

A

expensive

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11
Q

cognitive reserve after recovery from acute effects of TBI

A

cognitive recovers to almost original magnitude but not quite

means you are more likely to reach the dementia threshold later on

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12
Q

examples of 4 types of animal model

A

blast injury
fluid percussion injury
weight drop
controlled cortical impact (CCI) injury

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13
Q

blast injury model

A

mimics impact from explosions on soldiers

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14
Q

fluid percussion injury model

A

mimics subdural haemorrhage
fluid injected
behavioural models carried out

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15
Q

2 types of weight drop model

A

Marmarou’s for generalised/diffuse/widespread concussion

Shohami’s for specific area of concussion and localised/focal effects e.g. on occipital lobe

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16
Q

controlled cortical impact (CCI) injury model

A

controlled slow impact on exposed dura of animal to induce TBI
mimics blood brain barrier disruption
measure brain

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17
Q

what does latest TBI research look for

A

changes in microglial or astrocyte activity in animals after impact

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18
Q

optical coherence tomography

A

new technology to detect TBI
look into retina (where glial progenitors are found)
look for early changes due to concussive injuries

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19
Q

benefits of optical coherence tomography

A

most non-invasive method

clearer than CTs or X-rays

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20
Q

which animal models would you use to model a compressed or fractured skull

A

penetrating injury so weight drop or blast injury model

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21
Q

which animal models would you use to model subdural haematomas or stroke

A

use fluid percussion model

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22
Q

3 locations of microglia

A

cortex
corpus callosum
hippocampus

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23
Q

features of cortical microglia

A

ramified
star-like projections
freedom and flexibility for movement

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24
Q

are microglia in corpus callosum ramified

A

no

not much room to develop outward ramifications

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25
Q

activated microglia in chronic/long-term disease

A

enter rod-like state
lay down layers of individual rods for further protection
can inter-loop between amoeboid or hyper-ramified state

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26
Q

activated microglia in acute disease

A

enter amoeboid-like state
pass through hyper-ramified state
phagocytose and mop up damaged cells

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27
Q

which cells activate microglia into M1 polarisation state

A

IL-1B
TNF-A
IFN-Y

Th1 cells

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28
Q

effect of M1 microglia

A

inflammation

neuronal cell death

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29
Q

which cells activate microglia into M2 polarisation state

A

IL-4
Il-13

Th2 and Treg cells involved

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30
Q

effect of M2 microglia

A

release TGF-B
neuroprotective
anti-inflammatory

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31
Q

subtypes of M2 polarisation state

A

M2a, M2b, M2c –> secrete cytokines for generalised anti-inflammatory response
M2d –> secretes VEGF for angiogenesis

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32
Q

cytokines secreted by M2 subtypes

A

M2a: Il-4
M2b - IgG
M2c - IL-10

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33
Q

M0 polarisation state

A

resting state

secretes BDNF and IGF-1

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34
Q

what does DAM stand for

A

disease associated microglia

35
Q

what are disease associated microglia

A

new protective microglia
commonly identified in people with ALS
CX3CR1 receptor

36
Q

function of DAM

A

makes area surrounding insult (plaque deposition) secrete anti-inflammatory cytokines to prevent further damage

37
Q

microgliosis/astrogliosis overview

A

over reactiveness of glia after resting state

38
Q

what characterises TBI neuro-inflammation

A

reactive gliosis

39
Q

drug to change polarisation state from M1 to M2

A

bexarotene

enhances APOE protein
enhances IL-4 and IL-10
inhibits ROS and TNF-a

40
Q

TSPO

A

radio-ligand that gives indication of microglia activity in vivo using PET imaging

41
Q

benefits of TSPO

A

very specific marker for microglia

microglia express the protein in membrane

42
Q

GFAP

A

marker in imaging for astrocytes

astrocytes express the protein- so it is stained

43
Q

examples of therapeutics targeting M1/M2 subtypes

A

minocycline
lipid lowering drugs
HDAC inhibitors

44
Q

HDAC inhibitors mechanism of action

A

prevent removal of acetyl group on histones
histone wrapping is relaxed/less condensed
gene transcription is activated

45
Q

lipid lowering drugs function

A

important for immunomodulation

46
Q

minocycline

A

target microglia and inhibit their activation to suppress innate immune response
also down-regulate release of pro-inflammatory cytokines (e.g. TNF-a)

47
Q

genetic biomarkers for prediction of vulnerability for TBI

A

APOE
TREM2
BDNF

48
Q

BDNF

A

growth factor actively secreted by microglia

49
Q

benefits of CCI model

A

different parameters of injury (depth, velocity of impact) can be controlled to change the severity of the TBI induced

no rebound concussive events –> results are reliable

mimics concussion, axonal damage and BBB disruption

50
Q

disadvantage of CCI model

A

craniotomy (surgical opening into the
skull) is needed –> requires technical expertise

invasive

51
Q

method of Marmarou’s weight drop model

A
  • animal’s skull exposed by midline incision so a steel disc can be fixed on (to prevent bone fracture)
  • rats placed onto deep foam bed
  • a column of brass weights falls from a designated height through a tube onto the steel disc
52
Q

method ofl:

A

animal is anesthetized
midline incision is made exposing skull
stainless steel disc is attached in a central location
animals are then placed on a foam bed
impact is generated by free-falling weights
weight drop is delivered to one side of the unprotected skull

53
Q

injury produced by Shohami’s weight drop mode

A

reproduces neuronal and axonal pathology that is scattered throughout the cerebrum and brainstem. Depending on the severity of the injury, the induced brain injury results in hemorrhages, neuronal cell death, astrogliosis, diffuse axonal injury, and cytotoxic brain edema.

54
Q

advantages of weight drop model

A

cheap
easy to set up
good replicability
severity of the injury can be manipulated based on changing pre-impact parameters such as varying the weights and weight height

55
Q

limitations of weight drop model

A

control of parameters is less than CCI

more accidental deaths of rodents

56
Q

aim of fluid percussion model

A

to mimic non-fracture TBIs

57
Q

how is TBI induced using fluid percussion model

A 
a pressure pulse is targeted at the intact dura via a craniotomy
the pulse (or “percussion”) is generated
when a pendulum strikes the piston of a reservoir of fluid

injury induced can cause contra-lateral or unilateral damage

58
Q

limitations of fluid percussion injury model

A

use of fluid means less control over strength of parameters
high incident of accidental death of rodents
altered ionic homeostasis (increase in Ca2+)
EEG depression, motor and cognitive deficits induced

59
Q

aim of blast injury model

A

to investigate how military blast waves affect the brain by inducing mainly diffuse injuries

military personnel often suffer from TBI without any external injuries

60
Q

consequences of injuries from blast waves

A

often lead to motor coordination, spatial memory and social recognition impairments

61
Q

what is the acute function of activated microglia in TBI

A

to remove cellular and molecular debris to restore normal neuronal environment

62
Q

DAMPs

A

damage associated molecular patterns

stimuli released by damaged cells which can stimulate pro-inflammatory events –> further tissue damage

63
Q

phenotype shift of microglia in chronic TBI

A

microglia polarisation phenotype shifts from M2 to M1 in chronic TBi

64
Q

noxious stimuli released from activated microglia

A

ROS
pro-inflammatory cytokines
nitrogen species
excitatory neurotransmitters (e.g. glutamate) –> neurotoxicity

65
Q

development of assistive technology for TBI patients

A

talking clock/calendar –> announces date and time at push of a button

large print calendar or checklist to help with daily routine and activities or appointment reminders

ultra key seeker to help locate lost keys

shake awake –> vibrating alarm clock

pill alert –> alarm feature for taking medication

66
Q

importance of HLA subtype

A

HLA subtype can affect vulnerability of developing autoimmune diseases (TBI has autoimmune effects)

67
Q

use of diuretics to treat TBI

A

reduce the amount of fluid in tissues and increase urine output
Diuretics given intravenously help reduce pressure inside the brain.

68
Q

vorinostat

A

ahistone deacetylase (HDAC) inhibitor.

inducing iNOS/Nrf2/ARE pathway reduces the amount of oxidative stress and therefore has neuroprotective effects.

69
Q

anti-seizure drugs

A

seizures common for TBI patients during the first week after their injury.
drugs may be given during the first week to avoid any additional brain damage that might be caused by a seizure.

70
Q

coma-inducing drugs

A

a brain in a temporary coma needs less oxygen to function

71
Q

why might putting a patient with TBI into a coma be useful

A

blood vessels are often compressed by increased pressure in the brain
therefore are unable to supply brain cells with required amounts of nutrients and oxygen

72
Q

what is PU.1

A

transcription factor expressed by microglia in the brain

controls microglia development and function

73
Q

glasgow coma scale

A

Measures a persons functioning:

Ability to speak
Ability to open eyes
Ability to move

74
Q

identifying features of severe TBI

A

person unconscious for more than 24 hours

memory loss lasts more than a week

75
Q

identifying features of moderate TBI

A

person unconscious from 30 minute up to 24 hours

memory loss lasts between 24 hours and 1 week

76
Q

identifying features of mild TBI

A

person not unconscious or for less than 30 minutes

memory loss lasts less than 24hours

77
Q

advantage of x-ray

A

small radiation dose

78
Q

method of ct scan

A

Computerised tomography

Scan takes X-rays from many angles to create a complete 3D picture

79
Q

pros/cons of ct scan

A

+
Can quickly show bleeding in the brain,
bruised brain tissue and other damage

-
Radiation dose exposure higher than
xray
Still lacks some detail

80
Q

disadvantage of MRI

A

takes too long

however good detail

81
Q

what is an EEG

A

electroencephalogram (measures electrical activity using electrodes)

82
Q

pros/cons of EEG

A

Non invasive and no radiation
higher sensitivity

Doesn’t give such a good image of where the damage is and to what extent it has reached

83
Q

problems which require surgical treatment

A

Haematoma –> bleeding puts further pressure on the brain, damaging tissue (remove haematoma)

skull fracture –> removal of pieces of
skull in the brain

Bleeding in the brain –> surgery in order to stop it

pressure inside skull –> relieved by draining accumulated
CSF or making a window

84
Q

supportive care methods for CTE as there is no cure or treatment

A

Calming environment –> Reducing clutter and distracting noise makes it easier for patients to focus and function, reducing confusion and frustration.

Reassuring responses –> Avoid correcting or quizzing the patient. Reassurance and validate their concerns.

Modify tasks –> Break tasks into easier steps and
concentrate on success, not failure. Create structure &
routine in their day to reduce confusion.

Regular exercise –> Promotes sleep, motor skills, lessens
depression, creates calming effect.

Games and thinking activities –>Helps slow cognitive
decline

Night-time rituals –> Establish calming bedtime rituals as behaviour is often worse at night. Leave night light on to prevent disorientation

TMS exam (22 decks)

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