Brain Damage and Neuroplasticity: Neuronal Response to Damage

Neuronal Degeneration

  • Neuronal degeneration involves the breakdown or death of neurons, occurring in normal development and disease. The process varies based on the cause of damage, neuron activity, and glial cell response.
  • Exotomies, or axon cutting in controlled environments, are used to study degeneration.
  • Two main types of degeneration:
    • Anterograde degeneration: Occurs in the distal part of the axon, away from the cell body. When an axon is cut, the signal from the cell body to the next neuron is disrupted, leading to breakdown in the forward direction. It happens rapidly; the axon part swells within hours and breaks apart in a few days.
    • Retrograde degeneration: Moves backward toward the cell body from the point of signal transmission. It is slower, with changes in the cell body appearing one to two days post-injury.
  • Cell body responses to injury:
    • Degeneration: The cell shrinks, often leading to apoptosis (programmed cell death) or necrosis (uncontrolled cell death).
    • Regeneration: The cell enlarges, indicating an attempt to heal and regrow the axon. However, if the regrowing axon fails to connect with the correct target, the neuron may still die.
  • Transneuronal degeneration: Damage spreads through connected neural networks. It can occur in two directions:
    • Anterograde: Spreads forward to the next neuron.
    • Retrograde: Spreads backward to the preceding neuron.
  • Glutamate cascade: Damaged neurons release excessive glutamate, overstimulating nearby cells. This causes calcium overload and further cell death, exacerbating the original injury.

Neuronal Regeneration

  • Neurons do not regenerate equally across species. Invertebrates regenerate neurons effectively, but mammals, especially adult humans, have limited regeneration capacity.
  • In mammals, the peripheral nerve system (PNS) can sometimes regenerate, while the central nervous system (CNS, i.e., brain and spinal cord) has very limited regeneration.
  • Neurogenesis (new cell growth) can occur in the hippocampus, but this is different from axon regrowth.
  • Peripheral Nerve System (PNS) Regeneration:
    • After axon damage, regrowth starts at the proximal stump within two to three days.
    • If the myelin sheath is intact, the axon can follow it back to the target neurons for reconnection.
    • If myelin is damaged or misaligned, regrowth can go off track or fail.
    • Schwann cells in the PNS clear debris, release growth factors, provide energy and nutrients, and create a pathway for regrowth.
  • Central Nervous System (CNS) Regeneration:
    • Poor regeneration is due to the glial environment.
    • Oligodendrocytes (instead of Schwann cells) release chemicals that inhibit growth.
    • Astrocytes form a glial scar, creating a physical barrier to reconnection.
    • Damaged axons often fail to connect and eventually die rather than regenerate.

Neuronal Reorganization

  • The brain can reorganize itself in response to experience and damage by reassigning functions to new areas when pathways are damaged. This has been shown in both animal and human studies.
  • Echolocation in blind individuals:
    • Blind individuals use clicking sounds to perceive their environment, similar to bats.
    • Brain scans show that the visual cortex, normally used for sight, becomes active during echolocation, processing sound-based spatial information.
    • This demonstrates the brain's ability to repurpose areas for different functions based on need.
  • Mechanisms of neuronal reorganization:
    • Collateral sprouting: A slow, long-term process (days to weeks) where healthy neighboring neurons grow new axon branches to reconnect to damaged areas, forming new synapses and restoring function.
    • Release from inhibition: Rapid rerouting of signals using existing connections. Inhibitory signals that keep certain brain pathways inactive are reduced or lost after injury, allowing previously silent pathways to become active. This occurs within minutes to hours but is limited to nearby areas.
  • Figure 10.19 in textbook: Demonstrates how release from inhibition and collateral sprouting work together.
    • When a nerve from region B is damaged, inhibitory axons release from inhibition.
    • Nearby neurons connected to area A take over available axons and start responding.
    • Over time, these neurons grow new axon branches (sprouts) to cover a wider area, replacing lost connections.

Cognitive Reserve, Brain Reserve, and Adult Neurogenesis

  • Cognitive reserve: A person's ability to cope with brain damage using mental flexibility and problem-solving skills, which is often determined by executive function.
    • Built through life experience, education, occupational skills, general intelligence, cognitive, social, and physical activities.
    • Higher cognitive reserve may lead to better apparent recovery by finding alternative ways to perform tasks.
    • In dementia, high cognitive reserve can delay symptom recognition, leading to later diagnosis and missed early intervention opportunities.
  • Brain reserve: Refers to physical characteristics of the brain that offer protection, such as premorbid brain volume, healthy white matter, and larger brain size.
    • These features may delay the point at which damage causes noticeable problems, providing a buffer zone before functional decline.
  • Adult neurogenesis: Formation of new neurons in the adult brain.
    • Observed in the hippocampus of rat brains after injury, where new neurons can travel and connect with other neurons.
    • In humans, a case study found newly formed neurons in the hippocampus of a stroke patient, but they failed to connect before the patient's death one week later, leaving it unclear if functional neurogenesis occurs in the human brain.

Prevention

  • Focus on preventing or delaying the onset of diseases like Alzheimer's, rather than just treating symptoms post-diagnosis.
  • Risk factors for cognitive decline:
    • Non-modifiable: Age and genetics.
    • Modifiable: Lifestyle, environment, and behaviors like sleep, cognitive activity, physical activity, and diet.
  • Sleep:
    • Deep sleep consolidates memory and clears waste products like amyloid and tau through the glymphatic system.
    • Enhancing slow-wave sleep may prevent Alzheimer's disease; acoustic stimulation is being studied to boost delta wave activities.
    • Deep sleep is a brain maintenance system, and better sleep may protect cognitive health, but more research is needed.
  • Cognitive activities:
    • Mentally stimulating tasks that challenge the brain and promote neural engagement, such as reading, writing, studying, learning a new language, playing musical instruments, solving puzzles, and engaging in social activities.
    • These activities promote synaptic plasticity and may enhance cognitive reserve.
    • Some longitudinal studies suggest that regular cognitive activity is associated with a lower risk of developing Alzheimer's disease.
    • Brain scan studies show that cognitively active older adults tend to have larger gray matter volumes.
    • Cognitive training, which involves computer-based tasks designed to improve specific cognitive functions, shows some promising results for improving performance within the training setting.
  • Physical activity:
    • Animal studies show that physical activity increases hippocampal neurogenesis and brain-derived neurotrophic factor (BDNF), which supports brain health.
    • Exercise supports other brain-friendly factors like better sleep, mood, and heart health.
  • Diet:
    • The effects of diet vary from person to person and depend on overall health and comorbid conditions. Healthy eating is unlikely to be harmful and may be beneficial.
  • Critical Thinking:
    • When evaluating claims about Alzheimer's prevention, assess the supporting evidence and be cautious about advice, even from well-known figures.