Lecturer: Dr Lucy Patston
Girl living with half her brain
Lundy: Chapter 4 Tortura: PDF provided on Moodle Lundy-Ekman. Neuroscience: Fundamentals for Rehabilitation, 4th Edition. W.B. Saunders Company, Kandel et al. Principles of Neural Science, 5 th Edition. McGraw Hill, Tortura & Derrickson. Principles of anatomy and physiology, 13 th Edition. Wiley
What is neuroplasticity Central chromatolysis and Wallerian degeneration Axonal injury in the PNS Mechanisms for recovery in CNS
Be able to discuss cellular processes after injury (central chromatolysis & Wallerian degeneration) Be able to name and discuss two mechanisms of sprouting in the PNS Be able to name and discuss four mechanisms for synaptic recovery in the CNS Be able to explain why there is no repair of damaged axons in the CNS
Capacity of nervous system to adapt to change ◦ Learning ◦ Injury Old thinking – cortical representations static upon reaching adulthood, then: 1992: Canadian researchers discovered epidermal growth factor (EGF) stimulated cells from adult mice brains to proliferate into neurons and astrocytes 1998: Human hippocampus seen to show significant number of new neurons
Now we know – brain is dynamic structure, changing constantly through experience ◦ Use it or lose it! Changes: sprouting new dendrites, synthesis of new proteins, changes in synaptic contacts Despite this, neurons have limited ability to regenerate (replicate and repair themselves) Change can be anatomical, physiological or pharmacological
Anatomical ◦ Studies showing cortical motor maps change upon learning new skill – piano ◦ Recovering from stroke with interventions aimed at motor movement etc. (fMRI studies) Physiological ◦ Refinement of synaptic connections by experience ◦ E.g., music, doing stuff (dancing, swimming), emotional or social development Pharmacological ◦ Adaptation of synapses after damage, injury or toxic insult Forms basis of addiction/withdrawal
Injuries damaging or severing axons may be recoverable Injuries to cell bodies, however, usually cause death of the neuron In PNS damage to dendrites and myelinated axons may be repaired in cell body remains intact and if Schwann cells remain active In CNS little or no repair of damage occurs (even when cell body intact, a severed axon cannot be repaired or regrown) ◦ NB: This is not to say that new neurons/synapses do not grow
hours after injury, cell body undergoes central chromatolysis ◦ parts of the cell body break down/dissolve (Nissl bodies); nucleus moves toward periphery of soma; presynaptic terminals retract Apoptosis (cell death) may then occur
By Day 3-5 after an axon is severed, ◦ part connected to cell body is called proximal segment ◦ Part isolated from cell body is called distal segment Cytoplasm leaks out and segments retract from each other Distal segment then undergoes process called Wallerian degeneration
Axon swells, breaks, terminal buttons degenerate Myelin sheath pulls away (but neurolemma remains intact) Glial cells tidy up debris Schwann cells multiply (mitosis) and grow toward each other and may form a regeneration tube
Regeneration tube acts as protection and guidance for axon to regrow across injury site (if small enough)
Common due to long-range axons not sheltered by skull or vertebral column Axons may be severed by knives, machines etc. Axons may undergo repair if: ◦ 1. cell body is intact ◦ 2. Schwann cells are functional ◦ 3. Scar tissue has not occurred Regrowth of damaged axons called sprouting 1.Collateral (presynaptic death) 2.Regenerative (postsynaptic death)
Functional regeneration of axons occurs more frequently in PNS than CNS Nearly complete lack of neurogenesis in CNS due to ◦ (1) inhibitory influences from glial cells (oligodendrocytes) Possibly mechanism that stops axonal growth in development once target region is reached? (see Development lecture) ◦ (2) absence of nerve growth factor (NGF) by Schwann cells 1-1.5mm growth per day Problematic when new innervation is inappropriate (e.g., wrong muscle) ◦ Unintended movements named synkinesis usually short- lived
Same processes after SCI and TBI ◦ Axonal retraction ◦ Wallerian degeneration (WD) ◦ Central chromatolysis In CNS most damage occurs hours/days afterwards, due to cellular cascade: ◦ Increased permeability of axons ◦ Dysregulation of Na + -Ca 2+ channels causing influx of Ca 2+ Ca 2+ influx -> swelling/breaking/chromatolysis/WD This causes diffuse axonal injury/disconnection SCI: Spinal cord injury TBI: Traumatic brain injury
Glial scars form physically preventing axonal regeneration Astrocytes and microglia release growth- inhibiting factors (Nogo) Oligodendrocytes have no NGF, but Nogo instead! Animal tests have shown that administering a Nogo inhibitor after injury improves sprouting and functioning
Mechanisms for recovery in CNS: 1.Recovery of synaptic effectiveness 2.Denervation hypersensitivity 3.Synaptic hypereffectiveness 4.Unmasking of silent synapses
Swelling that produced pressure on presynaptic cell resolves and normal transmission is resumed
Increased sensitivity to other, nearby, presynaptic cells due to additional receptors
Larger than normal amounts of neurotransmitter released to remaining synapse
Unused synapses are lurched into action!
Cortical maps can be modified by experience ◦ E.g., violinists have enlarged finger representations for the left hand fMRI studies document functional recovery after stroke. ◦ Activity in somatosensory cortex shifts to more bilateral after stroke and then back to lateralised as recovery progresses Reorganisation seen in deaf and blind individuals. ◦ Cochlear implants after age 7 activate non-usual cortical areas. ◦ Congenitally blind ppl use occipital cortex for reading Braille and memory
Intensity and time between injury and rehab influence recovery Prolonged inaction promotes adjacent loss of cells/function ◦ Rat study: “rehab” 5 or 30 days post lesion ◦ 5 day group used impaired forelimb twice as well as 30 day group Task-specific rehab better ◦ Constraint-induced movement therapy (functional arm constrained in sling) shown to be better behaviourally and through imaging