Module 1 Flashcards
1
Q
Classification of TBI
A
Closed (blunt): dura remains intact - Acceleration/deceleration - Deformation of tissue Open (penetrating): open dura - Bullets, spears etc
2
Q
Primary TBI
A
- Mechanical events occurring at the time of the trauma
- Tears, lacerations, stretch, haemorrhage
- Preventable but not amenable to pharmacological treatment
3
Q
Secondary Injury
A
- Delayed biochemical and physiological events
- Oedema, NTs, ions etc
- Accounts for much of the neurological deficit that occurs after trauma
- The delay makes them a potential target for pharmacological intervention
4
Q
Types of Primary TBIs
A
- Skull fracture
- haemorrhage (space occupying)
- axonal injury: focal and diffuse
- diffuse vascular injury: petechial haemorrhages
5
Q
Primary Focal Vascular Injury (Extradural haemorrhage - haematoma)
A
- Involves arteries
- Form when bleeding occurs between the skull and the dura mater and the normally adherent dura is stripped from the bone
- Space occupying lesion
6
Q
Primary Focal Vascular Injury (Subdural haemorrhage - haemtoma)
A
- Bridging veins are damaged and bleed
- Space occupying lesions -> increased pressure
- Not as quickly as extradural as veins bleed much slpwer than arteries
- Often have a lucid interval -> onset of symptoms much slower
7
Q
Primary Focal Vascular Injury (Subarachnoid haemorrhage)
A
- Most common abnormality seen following head injury, usually minor
8
Q
Primary Focal Vascular Injury (Intracerebral haemorrhage)
A
- Are haematomas 2cm or greater in size, not in contact with the surface of the brain
- Caused by deformation and rupture of intrinsic blood vessels
9
Q
Primary Axonal Injury
A
- Can be focal and diffuse
- Axonal swelling are the histological markers of DAI
- DAI is most common cause of vegetative state, dementia, severe disability
- Most DAI occurs over time (secondary) therefore creating a window for therapeutic interventions
- Can also occur as primary injury due to direct laceration of axons
10
Q
Contusions
A
- ‘Brian Bruises’
- Occurs due to mechanical forces damaging small BVs and other tissue components (glia and nerve cells)
- Damage sets in motion a cascade of events leading to haemorrhage, delayed breakdown of BBB and infarction secondary to thrombotic occlusion of BVs
11
Q
Types of Contusions
A
- Coup: beneath impact site
- Contrecoup: opposite to impact site
- Intermediate coup: middle of brain
- Fracture contusions: occur beneath site of fracture
- Gliding contusions: caused by movement of the brain
12
Q
Lacerations
A
- Disruptions of neural paranchyma occurring at moment of injury
- Direct: penetrating injury from missiles or depressed skull fractures
- Indirect: secondary to tissue deformation by mechanical forces (nothing actually penetrates the skull)
13
Q
Diffuse Vascular Injury (DVI)
A
- Numerous small haemorrhages throughout the brain
- Common in white matter of frontal and temporal lobes
- Very common in patients who die within minutes of a closed head injury
14
Q
Secondary TBIs
A
- Focal or diffuse hypoxic-ischaemic injury
- Focal or diffuse brain swelling
15
Q
Hypoxic-Ischaemic Injury
A
- Is likely whenever there is a reduced content of oxygen in the blood or reduced blood flow to an area in the brain
16
Q
Diffuse brain swelling
A
- Occurs frequently after TBI and may contribute to raising ICP
- Occurs mainly in children and adolescents
17
Q
Post-Traumatic Oedema
A
- Accounts for 50% of all deaths following TBI
18
Q
Treatment for TBI
A
- Immediate surgery to control bleeding
- Monitoring and controlling ICP
- Insuring adequate BF to brain
- currently no effective therapeutic intervention for TBI
19
Q
Glasgow coma scale
A
- Tests for three pateint responses: eye opening, best verbal response, best motor response
- Scale 3 - 15
- 3 - 8: severe head injury
- 9 - 12: moderate head injury
- 13 - 15: mild head injury
- its use may be limited by confounding factors such as intoxication and ongoing medical treatment such as sedation
20
Q
Other Assessments of TBI
A
- In addition to GCS:
- duration of loss of consciousness
- post traumatic amnesia
21
Q
Concussion
A
- Functional rather than a structural impairment
- Two descriptions:
1. Describes a distinct pathophysiological entitiy with its own diagnostic and management implications, mainly seen in the context of sporting injuries
2. Describes a constellation of symptoms that arise after different types of TBI
22
Q
Diagnosis
A
- Usually very subjective, based on self-reports, which can be overstated or concealed
- SCAT3
23
Q
What happens to the brain following a concussion
A
- Mechanical injury
- Indiscriminate release of NTs
- Widespread ionic fluxes
- Ionic environment is the same inside and outside the cell
- > neuron can’t send any APs because there is no way to create an electric current
- > stops the brain from being able to communicate -> loss of consciousness and amnesia - Increased activity of membrane pumps to restore ionic gradient
- Hyperglycoloysis to generate more ATP
- ‘Energy crisis’: around 2-10 days afterward the brain has less glucose as the body isn’t able to keep up with the demand .: period of vulnerability
24
Q
Axonal Events Following a concussion
A
- Neurofilament compaction
- Microtubule disassembly and accumulation of axonally transported organelles
- Axonal swelling
25
Q
Post-Concussion Syndrome
A
- 5-10% of concussions will have symptoms that persist beyond 6 weeks
- There is no known cause for these persistent symptoms
- A prior history of concussions will increase the likelihood of PCS
26
Q
Repeated Concussion
A
- Once a person sustains a concussion, they are 4 times more likely to sustain a second one
- After several concussions, it requires less of a blow to cause the injury and requires longer to recover
27
Q
Long Term Effects of Repeated mTBI (concussion)
A
- Mild cognitive impairment
- Depression
- Neurodegeneration: dementia, parkinson’s, ALS, CTE
28
Q
Chronic Traumatic Encephalopathy
A
- Progressive tauopathy characterised by irregular deposition of hyperphyosphorylated (abnormal) tau
- Unique tau deposition observed in superficial cortical layers with epicentre at the base of the sulci (this is where the mechanical forces are concentrated) and surround BVs
- Cerebral atrophy, thinning of white matter pathways
29
Q
Tau
A
- Microtubule associated protein
- Helps with movement of proteins along the microtubule
- when it is bound to the MTs it assists in stability
- tau becomes unbound to allow the protein to move down the MT by addiding a phosphorylated tag to the tau protein
30
Q
Hyperphospharylated Tau
A
- phosphate tags accumulate, cant be taken off the protein -> cant attach to the MTs -> MTs become unstable -> inhibition of axonal transport
- also become sticky -> clump together -> can form neurofibrillary tangles
31
Q
Clinical Features of CTE
A
- One of two major initial presentations:
1. behaviour/mood variant - observed in younger patients (40yrs)
- increased aggression, anxiety and depression
- more impulsive and violent behaviours
2. cognitive variant - observed in older patients
- impaired episodic memory
- ‘dementia like’ symptoms
32
Q
SC Structure
A
- Cell bodies of sensory neurons located in ganglia
- cell bodies of motor neurons located in SC
33
Q
Secondary Injury
A
- delayed and potentially reversible molecular and cellular pathophysiological mechanisms
- these processes are characterised by neuronal cell death, astrocyte activatino, infiltration of peripheral monocytes and activation of resident microglia
34
Q
Secondary Injury: excitotoxicity
A
- Increase in extracellular glutamate following uncontrolled release with neuronal depolarisation
- Accumulation of intracellular calcium activates a number of calcium dependent enzymes, which degrade cellular structures and eventually cause neuronal degeneration
35
Q
Secondary Injury: oxidative stress
A
- caused by an increased production of ROS or decreased degradation (role of antioxidants)
- > disruption of plasma memb
- > oxidation of proteins
- > mutations in DNA
36
Q
Secondary Injury: Neuroinflammation
A
- post traumatic neuroinflammatino is characterised by glial cell activation, leukocyte recruitment and upreg of inflam mediators
- Both protective and detrimental effects for the progression of secondary brain damage have been associated with diff aspects of the immune response
37
Q
Microglia
A
- resident immune cell in the brain
- number of physiological functions: maintenance of tissue homeostasis, synaptic remodelling and secretion of neurotrophic factors
38
Q
Microglia following injury
A
- Among the first responders to cns injuries
- mobilised within the hour and continue to accumulate for over a month
39
Q
Microglial activation
A
- Resting microglia appear ramified with many short, fine processes, which allows them to sense changes in local environment
- Activated microglia appear amoeboid, spherical, lacking processes and containing numerous phagocytic vacuoles
40
Q
Microglia activation states
A
MI: detrimental - role: phagocytose and remove debris - cytotoxicity and tissue injury M2: beneficial - role: turn off immune response and switch to tissue repair - immune suppression and tissue repair Ideally after insult to brain: M1 -> M2
41
Q
Microglial activation: double edged sword
A
Exacerbate tissue damage via: - Pro-inflam cytokines - interferon gamma - oxidative metabolites - MMP-9 Also has beneficial effects: - phagocytose cellular debris and release anti-inflam cytokines
42
Q
Astrocyte function following insult to brain
A
- mount a pro-inflam response: clear debris, promote tissue repair, recruit peripheral leukocytes
- Form a barrier (glial scar) to limit spread of toxic environment created by secondary injury processes
43
Q
Neutrophils following acute brain injury
A
- attempt to clear cell debris by phagocytosis, release growth factor for repair
- also contributes to ongoing tissue injury following initial insult: release of ROS and MMPs -> amplify brain inflam response with more extensive activation of resident cells
44
Q
Inflammatory mediators
A
- Cytokines, chemokines, neuropeptides
- Regulate peripheral immune cell infiltration, microglial and astrocytic activation, apoptotic cell death, repair processes
45
Q
TNF-alpha
A
- Pro-inflam cytokine produced by activated microglia and astrocyte
- TNF knock out mice: do better initially but don’t recover as well later
46
Q
Chemokines
A
- The chemotactic cytokines, or chemokines, comprise a large group of inflammatory mediators that regulate leukocyte activation and migration
47
Q
*** lecture 4 checkpoint
A
do before test!
48
Q
Persistant Inflammation
A
- Following acute injury to the brain a subset of patients develop reactive microgliosis
- Reactive microgliosis can be defined as a microglial activation that occurs in response to neuronal damage, which is then perpetuated by further microglial activation and neurotoxicity
- Thus, a self-propelling and progressive cycle of microglial activation and neuron damage ensues
- May underlie the link between acute brain injury and increased risk of neurodegenerative diseases like AD’s
