Peripheral nerve injury & degeneration

Question 1

Types of neurons :

1. Pseudounipolar

Answer 1

In the DRG (most sensory neurons)

Question 2

2. Bipolar

Answer 2

Retina and spinal ganglia in the ear

Question 3

3. Multipolar

Answer 3

In the CNS (most common type)

Question 4

Structure of neurons :

Answer 4

Cell body : contain nissel’s bodies (aggregation of RER)
Dendrites : carry info from the periphery to the centre
Axons

Question 5

Structure of the peripheral nerve :

Answer 5

A collection of axons that are supported or myelinated by Schwann cells and connective tissue (endoneurium, perineurium, epineurium )

Question 6

Endoneurium
Perineurium
Epineurium

Answer 6

• connective tissue that surrounds each individual axon
• surrounds bundle of axons
• surrounds the whole peripheral nerve

Question 7

Schwann cell

Answer 7

A supporting cell responsible for myelination, they wrap around the axons and form myelin sheath (myelin sheath is a modified cell membrane which is composed of high amounts of phospholipids)

Question 8

Cell body

Answer 8

Produces all the nutrients that axon needs ( factory of neutrients )

Question 9

Respond to nerve injury :

Answer 9

Changes in the distal segment of the axon below the injury is called : WALLERIAN DEGENERATION, in which the axon is swollen and broken into fragments

( the distal part will be cut off all nutrients from the cell body )

Question 10

Role of macrophages :

Answer 10

Peripheral nerve injury induces distruptiom of axon/Schwann cell nerve unit, and then upregulates a variety of chemokines/cytokines and other factors to recruit monocytes/macrophages. The MQs contribute to Wallerian degeneration by removing the debris (clean up)

Question 11

The entire axon is destroyed within a…

Answer 11

week

Question 12

Changes in the PROXIMAL segment of the axon ABOVE the injury

Answer 12

similar changes to those that take place in the distal segment occur from the site of injury to the NODE OF RANVIER ABOVE the injury. The basal lamina of the Schwan cell, which will surround the degenerative axon will PERSIST.

Question 13

What do we see in a normal neuron ?

Answer 13

Central nucleus w/ a prominent nucleolus and a lot of Nissl’s granules (substances)

Question 14

Change in the neuronal CELL BODY from which the axon arises :

Answer 14

a) Chromatolysis : the cell body becomes fine, granular, dispersed throughout the cytoplasm
b) The nucleus moves towards the periphery of the cell
c) The cell body swells and becomes rounded
d) Synaptic stripping : synaptic terminals are seen to withdraw from the surface of the injured neuronal cell body and its dendrites and they are replaced by Schwan cells in the PNS and astrocytes/microglial cells in the CNS.

Question 15

Both changes in the neuronal cell body and proximal segment are called

Answer 15

Retrograde degeneration

Question 16

Schwann cells will be stimulated to stimulate macrophages to produces another subtype (M2 MQs) ,
What are MQs responsible for ?

Answer 16

Regeneration

• secrete cytokines (antiinflammatory cytokines)
• secrete growth factor
• stimulates Schwann cell proliferation

Question 17

The regeneration will start at the

Answer 17

Proximal segment bcs it is nearer to the cell body, and the schwann cells will proliferate forming a band (guide the sprouting of axons) and the axon starts growing (sprouting) at the direction of the band.

Question 18

Although there is discontinuation between the distal and proximal part,how are the axon and schwann cell are guided to reach the distal segment during regeneration?

Answer 18

The macrophages will secrete VEGF (vascular
endothelial growth factor) that will promote
angiogenesis ,and the capillaries will form a bridge by
the endothelial cells between the two ends, and along
the vascular bridge ,the Schwann cell with the growing
axon will grow into the distal segment,and then the
Schwann cell will start functioning by producing
myelin.

Question 19

What and Where do Schwann cells secrete so that the axon will grow in the correct direction?

Answer 19

In the DISTAL segment, they secrete attractive chemotropic agents

Question 20

Where do we find inhibitory factors and what is their function ?

Answer 20

In the PERINEURIUM, they are important to prevent the growth of axon outside the tract.

Question 21

What’s an important difference between PNS and CNS

Answer 21

Only PNS has the ability to regenerate

Question 22

Role of MQs in peripheral nerve degeneration

Answer 22

they are educated by the local injured microenvironment and are polarized to an anti-inflammatory phenotype (M2), that secret anti-inflammatory/growth supportive cytokines, this includes the regulation of Schwann cell differentiation, the promotion of Schwann cell remyelination, axonal support and angiogenesis, thus promoting peripheral nerve regeneration.

Question 23

Schwann cells proliferate in the

Answer 23

distal segments and become arranged in parallel cords (band) within the persisted basement membrane that create directional tubes that provide a sustaining substrate for axonal regrowth back to their original targets.

Question 24

What is the major cell type of the bridge ?

Answer 24

Macrophages,
(Check the pic in the note slide 14)
which secrete VEGF that promotes angiogenesis, the bridge has become vascularised and SCs migrate along the vasculature, taking the regrowing axons across the bridge and into the distal stump (c). The regeneration process is complete (d), once the axons reinnervate their original targets and the SCs recognising the axons, redifferentiate and the inflammatory response resolves.

Question 25

Sprouts from the axons grow from the …… stump to the …… stump toward the nerve’s end organs

Answer 25

Proximal , distal

Question 26

Mechanism of regeneration of Axons in the peripheral nerve :

Answer 26

The axons are attracted by chemotropic factors secreted by Schwann cells in the distal stump.
Growth-stimulating factors exist within the distal stump.
Inhibitory factors are present in the perineurium to inhibit the axons from leaving the nerve

Question 27

Degenerative cell body characteristics:

Answer 27

1. Swollen cell body 2.
The nucleus is located in the
periphery 3.
Disappearance of most of the
nissel’s bodies (chromatolysis)

Question 28

Recovery of the neuronal cell body :

Answer 28

Appearance of the clusters of Nissl material. b) Return of the nucleus to the cell center. c)
Decrease in the swelling of the cell body.

Question 29

Whats is the rate of axon growth ?

Answer 29

0.5-3 mm/day

Question 30

What happens when the axon does not penentrate the cord of Schwann cells ?

Answer 30

Its growth is not organized

Question 31

What happens when the axon fails to reach the target ?

Answer 31

The muscle will be more atrophic and may lose its function

Question 32

Where is the lower motor neuron located ?

Answer 32

Anterior horn of spinal cord and in the motor nuclei of the cranial nerves.

Question 33

Cranial nerves :

Answer 33

They are considered as peripheral nerves and the supply the head & neck.

Question 34

Factors affecting functional recovery of the peripheral nerve :

Answer 34

• 1) If the injury is crushed or cut or compression
)According to the type of injury, different types of regeneration and recovery will occur).
• 2) The site of crushed injury (if affecting the blood supply) Regeneration won’t be
is
normal.
• 3)The distance between the proximal and distal stump. The bigger the distance - the harder the regeneration
• 4) If the nerve is mixed. In a mixed nerve,the motor fiber will go to the sensory or the opposite ,so the regeneration may not be perfect in a mixed nerve.
• 5) The presence of infection at the site of injury. Infection affects the proliferation of Schwann cells and the anti-inflammatory function of macrophages
• 6) Inadequate physiotherapy to paralyzed muscles (physiotherapy is needed for the recovery of atrophic muscle otherwise it won’t return to its normal function).

Question 35

Complete cord transaction

syndrome

Answer 35

Loss of everything below the site of injury in both sides

Question 36

Poliomyelitis

Answer 36

Affect only the anterior horn (ex. LMN injury)

Question 37

ALS

Answer 37

Affect both UMN & LMN (mixed)

Question 38

Anterior cord syndrome

Answer 38

1- due to injury of the anterior spinal artery (supplies 2/3 of the anterior part of spinal cord).
2- Most of the sensation in both sides will be lost except proprioception bcs its in the posterior column (gracilis and cuneatus will be spared)
3. There will be an UMN lesion in both sides bcs the lateral corticospinal tract is affected.
4. Sensation of temperature, light touch, and pain will be lost in both sides

Question 39

Bone sequard syndrome :

Answer 39

1.
Total loss of all sensations - Ipsilateral hypotonic
paralysis which indicate LMN lesion (at the site of
lesion)
2.
IPSILATERAL loss of proprioception below the site of
injury ( the gracilis and cuneatus, which are
responsible of proprioception, carries inf from the
same side since they cross in the MEDULLA not the
spinal cord )
3.
CONTRALATERAL loss of pain and temperature
sensations (the spinothalamic tract, which is
responsible of these sensations carries info from
the opposite site)

Question 40

Syringomyelia

Answer 40

the development of a fluid-filled cyst (syrinx)
in the central canal within the spinal cord. Overtime, the cyst can enlarge and expand compressing the crossing of lamina 1 and 5 (spinothalamic tract) So pain, temperature, and light touch sensations are lost on BOTH SIDES. #Note: most of the time - it occurs in the cervical region

Question 41

Lesion to the corticospinal tract From the cerebral cortex to the pyramid Above the motor decussation →

Answer 41

UMN lesion of the contralateral side Example: vascular lesion of the cerebral cortex (Haemorrhagic lesion, thrombosis)(The cortex controls the opposite side of the body, so we will have contralateral paralysis)

Question 42

Weber’s syndrome

Answer 42

Occlusion of a branch of posterior cerebral artery -

supplies the midbrain

Question 43

Lesion of the lateral corticospinal Tract (in the spinal cord)–>

Answer 43

UMN lesion of ipsilateral side

Question 44

damage to the anterior corticospinal tract

Answer 44

No obvious weakness

Question 45

Lesion above the decussation (above medulla):

Answer 45

contralateral UMN lesion

Question 46

Lesion after crossing

Answer 46

UMN lesion Ipsilateral