Brain Damage and Neuroplasticity Notes

Causes of Brain Damage

• Part 1 focuses on the causes of brain damage, neurological disorders, and responses to nervous system damage.

• Dr. Seung Jae (Jesse) Lee, Biological Psychology Week 12 2025

Tumours

• Two main types: Encapsulated and Infiltrating.

• Encapsulated Tumours (e.g., Meningiomas)

  • Grow between the meninges.

  • Easy to identify on scans.

  • Surgically removable with minimal risk.

  • Generally good prognosis.

• Infiltrating Tumours (e.g., Glioblastomas)

  • Grow diffusely within the brain.

  • Difficult to treat or remove.

  • Generally poor prognosis.

  • LO1. Two types of brain tumors

Stroke

• Sudden onset cerebrovascular disorders.

• A leading cause of death and adult disability.

• Symptoms vary depending on the affected brain area.

• Infarct: Area of dead/dying tissue due to the stroke.

• Penumbra: Area surrounding the infarct that is affected and becomes dysfunctional; a zone that could still be saved.

• LO2. Two types of Stroke: Hemorrhage and Ischemia

• Brain gets oxygen & glucose from 4 major arteries: 2 vertebral (inside spine), 2 internal carotid (in neck)

• Arteries join at the Circle of Willis

  • Allows backup circulation if one artery is blocked.

  • Helps supply the penumbra with minimal blood flow.

  • Buys critical time for treatment.

Types of Stroke

• Cerebral Haemorrhage: Bleeding in the brain.

  • Commonly caused by a burst aneurysm.

  • Can also be caused by head trauma.

• Cerebral Ischemia: Disruption of blood supply to the brain.

  • Thrombosis: Blood clot, air bubble, etc., that forms and causes a plug.

  • Embolism: A thrombus that has travelled from elsewhere.

  • Arteriosclerosis: Narrowing of blood vessels.

Brain Damage from Ischemia

• Takes a while to develop – substantial neuron loss typically seen 24-48h later.

• Does not occur equally across the brain – some neurons are more susceptible than others.

Glutamate Cascade

1. Neurons stop getting oxygen and glucose.

2. Release glutamate uncontrollably & accumulate in the synapse.

3. Glutamate activation opens Ion channels (e.g., NMDA receptors) & Allow sodium and calcium Influx.

4. Sodium and calcium influx triggers further glutamate release — continuing the cascade.

• Too much of this inflow can overload the cell, leading to swelling, stress, and eventually cell damage or death.

Traumatic Brain Injuries (TBIs)

• Can be penetrating or closed head.

• Closed head TBIs are extremely common – 50% of people will experience at least one.

• In AU there are > 700,000 people with brain injuries affecting their daily function.

• LO3. The two sorts of closed-head traumatic brain injuries (TBIs)

Contusions

• Damage to the cerebral circulatory system resulting in haemorrhaging.

• Occur when the brain hits the inside of the skull.

Mild TBI

• Occur when a blow to the head disrupts consciousness – “concussion”.

• No contusion or structural damage.

• Effects on cognition, motor movements and neurological function can last many years.

Chronic Traumatic Encephalopathy

• Caused by repeated TBIs – often seen in athletes (e.g., professional footballers, fighters).

• Dementia/cognitive impairment and cerebral scarring.

Other Causes of Brain Damage

• Inflammation caused by infection is called encephalitis

  • Can be bacterial (e.g., meningitis, syphilis) or viral (e.g., rabies).

• Neurotoxins (exogenous or endogenous).

• Genetic Factors.

• Apoptosis (Programmed Cell Death) Vs Necrosis :

  • LO4. Describe two different types of infections of the brain

  • LO5. Describe three different types of neurotoxins.

  • LO6. Discuss the symptoms of Down syndrome and what causes this disorder.

  • LO7. Explain the difference between apoptosis and necrosis.

Neurological Diseases

• Part 2 focuses on different neurological diseases such as Alzheimer’s, Huntington’s, Parkinson’s, Epilepsy, and Multiple Sclerosis.

• Dr. Seung Jae (Jesse) Lee, Biological Psychology Week 12 2025

Alzheimer’s Disease

• Most common form of Dementia.

• Affects ~50 million people worldwide.

• Clear genetic vulnerability within families.

• Characterised by:

  • Accumulation of beta amyloid plaques.

  • Accumulation of tau (neurofibrillary tangles).

  • Neuronal degeneration particularly in the hippocampus, amygdala & entorhinal cortex.

  • Declines in memory & cognition.

  • Functional impairment.

  • Confirmed post-mortem.

  • LO12. Describe the symptoms of Alzheimer's disease and evaluate the amyloid hypothesis.

Medical Treatments

• Acetylcholinesterase Inhibitors

  • Individuals with AD have less acetylcholine, which is essential for neuronal signalling.

  • By inhibiting the breakdown of acetylcholine, neuronal function can be improved.

  • Acetylcholinesterase inhibitors can help delay progression of cognitive decline but do not otherwise affect AD trajectory or development.

• Amyloid Treatments such as monoclonal antibody treatments

  • Bind to amyloid to reduce amyloid burden within the brain.

  • Works better in animal models than in human studies.

  • Mixed and underwhelming improvements in cognitive status and brain health.

• Medical treatments rely on diagnosis – is it too late??

• There are many avenues of research investigating prevention.

Parkinson’s Disease

• Progressive motor disorder.

• Occurs in 1% of the population over 55.

• More often in males.

• No single cause.

• Symptoms include:

  • Tremor or stiffness in fingers.

  • Tremor at rest.

  • Muscular rigidity.

  • Slowness of movement.

  • Mask-like face.

  • Severe cognitive deficits not guaranteed.

  • Parkinson’s Disease with Dementia.

  • LO9. Describe the symptoms of Parkinson’s disease and some treatments for this disorder.

• Degeneration of dopamine neurons in the substantia nigra.

• Lewy bodies: clumps of alpha-synuclein.

• Treatment is with L-DOPA, which helps alleviate symptoms but does not improve disease progression.

• Deep brain stimulation of subthalamic nucleus for medication resistant symptoms.

Huntington’s Disease

• Progressive motor disorder.

• Clear genetic basis:

  • Single mutated dominant gene: Huntingtin.

  • First symptoms appear ~ age 40.

  • Huntingtin protein accumulates in the striatum (caudate and putamen).

  • Cell death.

  • Destroyed connections with the cortex.

  • Neuronal loss/brain changes 10y prior to clinical diagnosis.

  • Chorea: Impairments in involuntary and voluntary movements.

  • Cognitive deficits.

  • Psychiatric symptoms.

  • LO 10.10 Describe the symptoms of Huntington’s disease and explain its genetic basis.

Responses to Nervous System Damage

• Part 3 focuses on responses to nervous system damage, including degeneration, regeneration, reorganization, recovery, and prevention.

• Dr. Seung Jae (Jesse) Lee, Biological Psychology Week 12 2025

Neuronal Degeneration

• Neuronal degeneration is a complex process influenced by the cause of the degeneration, the activity of the degenerating cells, and by the nearby glial cells.

• In the laboratory, cutting axons results in two kinds of degeneration:

  • Anterograde degeneration.

  • Retrograde degeneration.

• Degeneration can spread to other neurons linked by synapses: Transneuronal degeneration.

  • Can also be anterograde or retrograde.

  • LO15. Explain the various types of neural degeneration that ensue following axotomy.

Neuronal Regeneration

• Regeneration of neurons:

  • Occurs more readily in invertebrates

  • Sometimes occurs in the mammalian PNS

  • Almost* non-existent in the mammalian CNS

Peripheral Regeneration:

• Begins from proximal stump

• Regrowth through intact myelin sheath

• If myelin is damaged, regrowth is more difficult

• Schwann cells myelinate the axons and are integral to regeneration

Central Nervous System Regeneration:

• Oligodendroglia myelinate axons – these actively block regeneration

• Reorganisation instead of regeneration

• *Neurogenesis in the hippocampus is possible

• LO16 Compare neural regeneration within the CNS vs. the PNS.

Neuronal Reorganisation

• In the CNS, reorganisation can occur after damage to certain areas or pathways

• This has been demonstrated in human and non-human models

Two potential mechanisms:

1. Collateral sprouting

2. Release from inhibition

   • LO17 Describe three examples of cortical reorganization following damage to the brain

Cognitive & Brain Reserve

• Cognitive Reserve: Educational & occupational attainment, general cognitive ability or intelligence, and engagement in activities that are cognitively, socially, and physically stimulating enable cognitive processes to be resilient to brain damage, neurodegeneration etc.

• Brain Reserve: structural characteristics of the brain at a given point in time (e.g., premorbid brain volume, white matter integrity)

• May protect against age and disease-related brain changes by impacting the threshold at which cognitive or functional decline emerge

Alzheimer’s Disease – Treatment Vs Prevention

• Medical treatments rely on diagnosis – is it too late??

• There are many avenues of research investigating prevention

• There are many factors that may offer protection against cognitive decline and dementia – modifiable and non-modifiable risk factors

  • Cognitive reserve

  • Lifestyle factors:

    • Cognitive activity

    • Physical activity

    • Diet

    • Sleep

Sleep and Alzheimer’s Disease

• Slow wave sleep (deep sleep) is linked to:

  • Memory and cognitive function

  • Clearance of brain toxins related to Alzheimer’s Disease

• In animals:

  • CSF and ISF continuously interchange

  • CSF influx is greatly increased during sleep

  • Glymphatic clearance of amyloid and tau from the brain

  • Amyloid and tau cleared from the brain into CSF during slow wave sleep

• In humans – much harder to study directly

Sleep Enhancement

• CAN WE ENHANCE SLOW WAVE SLEEP TO PREVENT AD?

  • Acoustic stimulation selectively enhances delta power in SWS

  • Not everyone shows the same response

  • SWS enhancement associated with cognitive improvement

  • Is acoustic stimulation effective in older adults?

  • Can this be effective for improving glymphatic clearance of brain toxins?

  • Who would benefit most from acoustic stimulation?

  • At what point is it “too late”? Diep et al (2020) Sleep

• https://youtu.be/NcFdAVrYfns - Cognitive Activities & Alzheimer’s Disease

Physical Activity

• Physical Activity has been linked to neuroplasticity and neurogenesis

• Treadmill exercise can increase hippocampal neurogenesis in mice

• Brain Derived Neurotrophic Factor (BDNF) is involved in neuroplasticity, neurogenesis and neuronal survival, and is increased with exercise

• Physical activity improves cognition in mouse models of Alzheimer’s, Parkinson’s and Huntington’s

• Exercise interventions in humans have had varied efficacy