Causes of Brain Dysfunction Flashcards
Cause of brain dysfunction
- Stroke
- Tumours, infections, toxins
- Traumatic brain injury and concussion
The brain is highly vulnerable to disturbances in blood supply - what can happen after seconds?
Blood vessels of the brain
neurological symptoms
The brain is highly vulnerable to disturbances in blood supply - what can happen after minutes?
irreversible damage
Cerebral arteries supply specific territories (3)
- Anterior cerebral artery: supplies to the front of the cortex (anterior side)
- Middle cerebral artery: supplying between anterior and posterior
- Posterior cerebral artery: supplying blood to posterior region
Stroke
neurological symptoms or signs resulting from diseases involving blood vessels
What happens to the actual brain tissue following a stroke?
- Infarct = dead or dying tissue (not getting any meaningful blood supply)
- Penumbra = dysfunctional area surrounding the infarct; this tissue may either recover or die
- Increase in infarct can show progressive “dying” of brain tissue
Strokes are the _ leading cause of death in Canada
3rd
_ of people 65+ in Canada have had a stroke
10%
Signs of stroke: F.A.S.T.
- Face
- Arms
- Speech
- Time (to call 911)
Consequences of strokes are varied but include (4)
- memory (amnesia),
- language (aphasia),
- motor function (paralysis),
- consciousness
Stroke risk factors
- High blood pressure
- High cholesterol
- Diabetes
- Smoking
- Cardiovascular conditions
- Psychosocial stress (what happens to you in your life)
What can count as psychosocial stress?
Lack of access to quality food, inadequate public health education, and experiences of discrimination all increase risk and worsen outcomes
Strokes are either
- Ischemic = blockage of a blood vessel
- Hemorrhagic = bleeding from a vessel
Types of ischemic stroke
Ischemic stroke
- Thrombosis
- Embolism
- Arteriosclerosis
Thrombosis
Types of ischemic stroke
Ischemic stroke
Thrombosis: occlusion due to blood clot or other substance
Embolism
Types of ischemic stroke
Ischemic stroke
results from a moving Thrombus; formed from somewhere else (EX: remaining matter - fat, oil, air bubble - from a surgery)
Where can either (thrombosis or embolism) form?
Ischemic stroke
arterial or venous
Arteriosclerosis
Types of ischemic stroke
Ischemic stroke
thickening, hardening, and narrowing of arteries due to fatty plaque build up (associated with high cholesterol) (“artery” + “hardening”)
Damage due to ischemic stroke (3)
Ischemic stroke
- Takes a while to develop (hours to days)
- Some brain areas are more vulnerable (e.g., hippocampus)
- Multiple mechanisms of damage
Multiple mechanisms of damage
Ischemic stroke
- Excitotoxicity
- Cell death signaling
- Neuroinflammation
- Oxidative stress
Excitotoxicity
Multiple mechanisms of damage
excessive glutamate release, which is hard on the cells (binding to NMDA receptors)
Cell death signaling
Multiple mechanisms of damage
triggering a pathway of cell death
Neuroinflammation
Multiple mechanisms of damage
triggers microglia to clean up dead neurons
Oxidative stress
Multiple mechanisms of damage
As cells break apart, they start releasing reactive oxygen species that can damage other cells
Transient ischemic attack (TIA)
- Short-term interruption of blood flow causing neurological symptoms, but no lasting brain damage (sometimes called a “mini-stroke” but this is a little misleading)
- Highly predictive of future stroke
Hemorrhagic stroke
- Opposite of ischemic, where blood would be blocked - rather, blood is escaping from the area where we’d want it to be contained
- Outcome depends on which pocket is being bled into
What can cause a hemorrhagic stroke?
Aneurysm
Aneurysm
- Weakened vessel wall, blown up like a balloon from pressure (a hemorrhagic stroke can happen when aneurisms burst)
- Congenital or may develop from high blood pressure or accumulated damage
- Usually in arteries other than veins
Treatment for aneurysm
- Clipping
- Coiling
3 stroke treatments
- Tissue plasminogen activator (tPA)
- Therapeutic hypothermia
- Many other potential drug targets
Tissue plasminogen activator (tPA)
Stroke treatment
- injection, breaks up blood clots
- Only suitable for an ischemic stroke - breaking up the blockage
Therapeutic hypothermia
Stroke treatment
cooling to slow down/prevent secondary damage
Many other potential drug targets
Stroke treatment
e.g., astrocytes
Tumours
mass of cells growing independently of the rest of the body
Can divide tumours into different growths:
- Encapsulated
- Infiltrating
- Benign
- Malignant
Encapsulated tumor
grow within their own membrane
Infiltrating tumor
not self-contained; difficult to remove or destroy
Benign tumor
surgically removable with little risk of further growth in the body
Malignant tumor
tending to grow and spread; sometimes due to metastasis
3 types of tumors
- Meningiomas
- Glioblastomas
- Metastatic
Meningiomas
grow between the meninges
- Encapsulated
- Benign tumours (usually)
- Relatively positive prognosis
Glioblastomas
usually located in the cerebral cortex
- Infiltrating
- Malignant
- Less positive prognosis
Metastatic tumours
infiltrating tumours that grow from tumour fragments in other parts of the body (commonly breast or lung)
3 types of infections
- Bacterial
- Viral
- Parasitic
When bacteria grow in the brain they often lead to:
Infections
- Inflammation (encephalitis)
- The formation of cerebral abscesses (pockets of pus)
Where in the brain can bacteria infect?
The meninges (outer layers of wrapping around the brain), producing an inflammation called meningitis
Treatment for meningitis
antibiotics
**
Syphilis
a bacteria that spreads as an STI
What happens if syphillis infects the brain?
If syphilis infects the brain (then called neurosyphilis), it can cause general paresis: a mental disorder characterised by delusions and personality changes
Treatment for Syphilis
antibiotics
2 types of viral infections
- Nervous system-specific
- Indiscriminate
Example of a “nervous system-specific” viral infection
2 types of viral infections
rabies
Example of “indiscriminate” viral infection
2 types of viral infections
e.g., herpes simplex
COVID as a viral infection type:
In-discriminant: affects different systems
Limitations to knowledge about COVID-19
- Long-term effects still unknown
- Heterogeneous waves
- Who becomes a “case”?
What receptor does COVID act upon?
- Acts upon ACE-2 receptor
- Regulates a protein involved with blood pressure and inflammation
Example of a parasitic infection
- Neurocysticercosis: tapeworm in the brain
- Can be due to contact with fecal matter
Treatment for neurocyticercosis
antihelminthic treatments + treat possible resulting epilepsy
Neurotoxins
Toxins
Chemicals destructive to nerve issue
2 examples of neurotoxins:
- Mercury: can accumulate in the brain and produce a toxic psychosis; only dangerous when evaporated and inhaled
- Lead: accumulates in the body over time; exposure to lead can also lead to a toxic psychosis
- Even low levels of lead affect children’s learning and development
Traumatic brain injury:
brain injury caused by an outside force
Common TBI symptoms (the brain takes over many specific roles - therefore, injuries and symptoms depend on the area affected)
- Fatigue/exhaustion
- Headache
- Dizziness
- Nausea or vomiting
- Blurred vision
- Light sensitivity
- Noise sensitivity
Open-head injuries - 3 types
- Penetrating
- Preforating
- Richochet
Open head injuries
- Typically very severe
- High risk of infection and complications
Closed-head injuries - can be caused by all kinds of forces:
- Linear
- Rotational
- Angular
- Blast
- Indirect (e.g., body check to torso)…
What impacts can your brain make when impacting a fixed object?
- Coup (brain hitting front/anterior of skull)
- Countercoup (brain bouncing off and then hitting the back/posterior of skull)
What is a Contusion?
- “bruise” on the brain from slamming the skull
- Damage to the brain’s vasculature by stretching or tearing produces
hemorrhaging & hematoma (pooling blood)
How can axons be damaged due to TBI?
Diffuse axonal injury: injury to axons following a TBI; can be distal to site of injury
- Compression (inwards tug)
- Tension (outwards tug)
- Shearing (ripping from different directions of movement)
Why is the spectrum of TBI severity helpful?
- in differentiating cases
- identifying high/low scores
Aftermath of a single mTBI
usually full recovery within 12 weeks
Aftermath of multiple TBI
can lead to chronic traumatic encephalopathy (CTE)
What 4 clinical presentations can represent early signs of CTE?
Chronic traumatic encephalopathy (CTE)
- Dementia
- Inappropriate behaviours
- Memory problems
- Explosive behaviour
Tau proteins in healthy individuals vs. with CTE
- In healthy individuals, tau proteins stabilize microtubules (part of a healthy cell’s shape)
- In CTE, misfolded tau proteins accumulate (tauopathy) and seed their misfolding to other tau proteins (act as prions)
- Accumulate first in sulci and small vessels
When can CTE be diagnosed?
○ Diagnosed post-mortem (after someone’s death) based on accumulation of abnormal tau proteins
Why might TBI symptoms be delayed? (4)
- Inflammation (swelling) + dysregulated microglia
- Excitotoxicity (excess glutamate) + oxidative stress (unstable molecules) > “destructive cascade” of enzymes > cell death
- Mitochondrial damage > reduced energy generation
- Deafferentation: death of cells that have lost their excitatory inputs
Why does the brain experience mental fatigue after a TBI?
- Occurs because the injured brain is not working efficiently and has to expend extra energy to perform tasks that previously did not deplete reserves.
- The brain becomes overloaded at low threshold and recovery is slowed compared to pre-trauma
