Brain Damage and Neuroplasticity - Causes of Brain Damage

Brain Tumours

• Two main types of primary brain tumours:
  • Originate in the brain.
  • Encapsulated tumours.
    • Example: Meningioma.
    • Grow between the meninges (thin tissue layers between skull and brain).
    • Meninges cushion between the skull and brain tissue.
    • Tumours push brain cells, causing dysfunction.
    • Often benign (grow slowly, don't invade, stick together).
    • Clear boundary, easy to detect on CT scans.
    • Easier to surgically remove with good prognosis (less likely to reoccur).
  • Infiltrating tumours.
    • Example: Glioblastoma.
    • Invade/spread into surrounding brain tissues, harder to treat.
    • Aggressive and grow diffusively (scattered spread).
    • Arise from glial cells (support neurons).
    • Glioblastoma mutation from astrocyte spreads easily.
    • Difficult to remove completely; often reoccur.
    • May require chemo or radiotherapy.
    • More likely in older adults.
• Brain tumours less likely to metastasize due to the blood-brain barrier.
• Metastatic brain tumours: 1 in 10 spread from lung cancer.
• Summary:
  • Encapsulated: kind, stick together, easy to remove, less likely to reoccur.
  • Infiltrating: hard to treat, aggressive, spread, often reoccur.

Stroke

• Sudden onset cerebrovascular event disrupting blood flow, causing tissue damage.
• Leading cause of death and adult disability.
• Statistics (Australia):
  • 45,000 Australians experience a stroke yearly (1 in 11 minutes).
  • 440,000+ Australians live with stroke after-effects.
• Symptoms related to affected brain area:
  • Hippocampus: memory loss.
  • Speech area (Wernicke's/Broca's): aphasia.
  • Motor cortex/basal ganglia: paralysis (opposite side of the body).
  • May mimic psychiatric disorders (disorganized thoughts/speech).
    • Psychosis.
    • Dementia.
    • Coma (spinal cord or subcortical area).
• Causes:
  • Insufficient blood flow.
    • Cerebral haemorrhage: burst blood vessel leaks blood.
    • Cerebral ischemia: blockage of artery cuts off oxygen/glucose.
• Infarct: immediate area of brain cell death (cannot be saved).
• Penumbra: area around the infarct, still has a chance to recover.
  • Goal: reduce penumbra before it becomes infarct.
  • Timely intervention improves outcomes by reducing permanent damage.
• Brain's Protection Mechanism: Circle of Willis.
  • Brain gets oxygen/glucose from four major arteries from the heart through the neck.
    • Two through spinal Two outside.
  • Arteries spread left and right, meet under the brain.
  • Circle of Willis helps arteries support each other; if one is blocked, others compensate.
  • Penumbra receives some blood from nearby vessels.
    • Brain emergency detour system (not perfect).
    • Buys time until treatment restores blood supply.

Cerebral Hemorrhage

• Blood vessel bursts, blood leaks into brain tissue.
• Leaked blood toxic, increases pressure within the skull.
• Causes:
  • External force (e.g., car accident).
  • Aneurysm: ballooning of an artery (congenital or acquired).
    • Risk factors: high blood pressure, high cholesterol, smoking.
    • Rupture causes direct injury to brain cells.
    • Toxic environment induces inflammatory reaction, oxidative stress, chemical damage, excitotoxicity (glutamine overstimulation).
  • Indirect damage:
    • Blood vessel was supplying oxygen.
    • Blood flow is blocked can cause ischaemia elsewhere.
• Arteriovenous Malformation (AVM):
  • Congenital blood vessel abnormality.
    • Artery -> Capillary -> Vein.
  • Capillaries tangled, form weak clusters.
  • Fragile vessels break open without warning.
  • Often asymptomatic until rupture.

Cerebral Ischemia

• Reduced or blocked blood flow, usually due to clot or narrowing.
• Brain cells shut down and die.
• Causes:
  • Thrombosis: clot forms inside blood vessel (plaque).
  • Embolism: clot forms elsewhere, travels, blocks artery.
  • Arteriosclerosis: vessels narrow/harden due to fat buildup.
• Damage not incidental; neuron loss visible in 24-48 hours.
• Neurons in hippocampus and cerebral cortex most sensitive to oxygen loss.

Cerebral Ischemia Glutamate Cascade

• Blood vessel blockage cuts off oxygen and glucose to neurons.
• Neurons release too much glutamate.
• Glial cells lack energy, cannot clear glutamate from synapses.
• Excess glutamate binds to NMDA receptors.
  • Triggers neuron to open iron gates (sodium/calcium).
  • Ions rush in causing more glutamate release (vicious circle).
    • Over-stimulation.
    • Muscle Spasms (tonic chronic diseases).
• Ion buildup causes neuron to swell, breakdown, and die.

Traumatic Brain Injuries

• Two main types:
  • Penetrating injury: object enters the brain.
    • Phineas Gage Case.
  • Closed head injury: skull intact, internal force injures brain.
    • Sudden acceleration/deceleration (e.g., car accident).
    • Brain cell bumps against inside of the skull.
• Statistics:
  • 1 in 2 people will experience one in their life.
  • 700+ people in Australia live with a brain injury that impacts daily function.
• Types of closed head injuries:
  • Direct impact: fall on the side of the head.
  • Acceleration/deceleration injury.
    • Coup injury: brain hits skull at first impact.
    • Contrecoup injury: brain hits back of skull.
  • Blast injury: pressure wave from explosion damages brain tissue (military setting).

Brain damage due to closed head injury:

• Contusion: brain bruise from hitting the skull.
  * Bruise causes Small hemorrhage inside brain cell.
  * Often happens with direct impact or cool contract cool injuries.
• Diffusive Axonal Injury: White metal track damage. Communication of neurons interrupted, can slow down recovery.
  * Doesn't show up on scan.
  * Affects thinking, attention, memory.
• Mild Traumatic Brain Injury (mTBI):
  * Bump on the head, conscious or loss of consciousness less than 30 minutes.
  * Memory of events before and after.
  * No clear abnormality on scans (CT/MRI).
  * Referred to as concussion or mild traumatic brain injury.
  * Encouraged to call mild traumatic brain injury as they symptoms can stay for quite a time.
• Post-concussion syndrome: prolonged symptoms (blurred vision, headache, slow thinking, attentional difficulties).
  * Inconsistent with injury severity.
  * Experience very severe symptoms even though mild.
• Chronic Traumatic Encephalopathy (CTE):
  * Progressive brain disease caused by repeated head trauma / multiple mild traumatic brain injury over time.
  * Scarring tissues in the brain through the scan.
  * Leads to memory problems, emotional dysregulation, dementia-like symptoms.
  * Found in boxers, rugby players, NFL players.

Other Causes of Brain Damage

• Bacterial infections:
  * Bacteria gets into brain, forms abscesses (pockets of pus).
  * Causes damage to brain and surrounding tissues.
  * Meningitis: PR or arachnoid dura mater brain layer infection, swelling, pressure (life-threatening).
• Viral infections:
  * Viruses (rabies, COVID) cause inflammation/nerve system damage.
  * Causes confusion, seizures, delusional situations.
• Syphilis:
  * Severe end, the syphilis virus Struggled to the brain and actually presented like someone having a severe dementia.
  * Memory problem, confusion and even personality change was occurred.
  * Syphilis virus to the brain (dementia-like symptoms) if left uncontrolled.
  * Well-managed with antibiotics today.
• Neurotoxins:
• Can be two different types:
  • External (exogenous) toxins( Heavy metal like lead or mercury can cause toxic psychosis. Vitamin C deficit. Nitro oxide.
    • This nitro oxide causes permanent damage to spinal cord, weakness of the limbic movement or very jerky or the severe tremor on their arm.
  • Internal toxins (Chronic high cortisol level).
    • Tricky: accumulate slowly, damage may be irreversible before symptoms appear.
• Genetic brain differences:
  * Down syndrome: extra copy of chromosome 21.
  leads to distinct facial features, intellectual disability and delays in development.
  * Williams syndrome: genetic condition with high social skill with social interest in music and but often present with attention deficit and specific learning difficulties.
  * Brains develop differently from the start, not damaged after development.
  * Not all brain changes are due to injury; some are genetic and develop atypically.
• Cell death:
  * Necrosis: messy, only happens when injury happens, involve with Inflammation and damage into nearby cells.
  * Apoptosis: programmed cell test. Just like clear up and control the area.
  * After brain injury, apoptosis can actually help by preventing further spreading of the damage.