Degeneration and Regeneration in PNS and CNS

Question 1

What is the perineurium? Significance?

Answer 1

CT sheath surrounding a bundle of axons making up a fascicle which the surgeon can suture together to encourage regeneration

Question 2

What is the alternate name for Schwann cell?

Answer 2

Neurolemmal cell

Question 3

What is an internodal segment vs myelin sheath?

Answer 3

Internodal segment - Innervation via one Schwann cell between nodes of Ranvier
Myelin sheath - the aggregate of the internodal segments covering the whole axon

Question 4

What is the clinical difference between a crush and transection injury?

Answer 4

Functionally they have the same defects.

Transection injuries have worse prognosis, however, as the continuity of the connective tissue sheath is interrupted.

Question 5

What portion of the axon degenerates in Wallerian degeneration?

Answer 5

Portion of axons distal to site of injury (no longer connected to CNS)

Question 6

What is the timeline of axonal breakup + phagocytosis in Wallerian degeneration for both CNS / PNS?

Answer 6

Entire length of axon distal to injury swells and looks beaded after 24 hours. Breaks apart within 3-5 days. Cell proliferation begins within neurolemmal sheath, which is the guide for regeneration of axons.

PNS: Phagocytosis of both axon and myelin is done by Schwann cells, with aid from macrophages, a process which can take months.

CNS: Site of lesion is walled off by hypertrophied astrocytes “astroglial reaction”, forming cysts that isolate the lesioned area from the rest of the CNS. Phagoytosis is done by microglia (resident macrophages), but astrocytes also help.

Question 7

What is the timeline for myelin degradation after injury?

Answer 7

1. Myelin retracts away from site of degeneration within 24-48 hours.
2. Myelin sheaths assume an abnormal heterogeneous morphology, with some thick and some thin spots.
3. Digestion by microglia / astrocytes in CNS, or macrophages + Schwann cells in PNS

Question 8

What are the three layers around myelinated axons in the PNS, from inside to outside?

Answer 8

1. Myelin sheath
2. Neurolemmal sheath - Cytoplasm of Schwann cell + basement membrane
3. External lamina / endoneurium connective tissue, around all axons

Question 9

What is chromatolysis? When does this occur and what else happens?

Answer 9

Breakdown of Nissl bodies in soma of neuron. Occurs in Wallerian degeneration, as nucleus moves eccentrically away from axon hillock. Nissl substance (RER) is dispersed into polyribosomes / free ribosomes. Cells are only basophilic along periphery of cell body.

Neuron will maintain this appearance until regeneration is complete.

Question 10

How can you tell if a neuron in Wallerian degradation is dying?

Answer 10

Nissl bodies disappear

Question 11

What is terminal sprouting? How can this lead to a problem?

Answer 11

Growth of many axons from end of transected axons (3-25). Crush injuries will have fewer since the myelin stays intact. Majority of branches will degenerate.

Sometimes these branches can double back on themselves for sensory input and cause a painful neuroma.

Question 12

When does myelination proceed? What determines this?

Answer 12

Within one week after axon regeneration is initiated, starts as a thin sheath first, growing away from center. Factors stimulating myelination are known, and do not necessarily depend on the size of the axon.

Question 13

What are four factors preventing total functional recovery of PNS?

Answer 13

1. Scar tissue - i.e. a gap between the two ends of the nerve so they can’t be pulled together
2. Incorrect reinnervation
3. Collateral sprouting
4. Rate of regeneration - muscles may atrophy before nerves can regenerate, as the rate of growth is only 1mm / day.

Question 14

What is meant by incorrect reinnervation?

Answer 14

Since terminal sprouting is random, axons can reinnervate the wrong structures (fast vs slow twitch muscle fibers)

Leads to complete anatomical regeneration without functional recovery

Question 15

What is meant by collateral sprouting? How does this help in ALS?

Answer 15

Normal nerves can also synapse on muscle terminals of damaged nerves. Allows a single nerve to take over the function of other nerve fibers that need to be regenerated. Not functionally the same, however.

ALS = loss of some nerve fibers, but maintenance of some others. Collateral sprouting can slow the progression of the condition.

Question 16

Why is the CNS not as good at regeneration as the PNS?

Answer 16

There is no difference in the intrinsic ability to regenerate between CNS / PNS. HOWEVER:

There are no neurolemmal / endoneurial sheaths in CNS to guide axon regen. Scar tissue / astroglial reaction is worse. CNS is too compact for regeneration. The level of synaptic interactions is much more complex.