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What is the difference between Wallerian degeneration AND axonal degeneration?

Wallerian degeneration is within the PNS

Axonal degeneration is within the CNS


The following refers to wallerian degeneration:

  1. The axon ____ to an injury will swell and die back.
  2. In "degeneration", what structure(s) is/are being destroyed?
  3. Macrophages act by doing what?

  1. The axon proximal to the injury will swell and die back.
  2. Only part of the neuron is destroyed, the axon
  3. Macrophages clean up the debris.


Regeneration of a damaged axon requires what?

Intact endoneurial connective tissue sheath


When a damaged axon swells up proximally, you can visualize this change microscopically.

  1. What would you call this structure on a cross section?
  2. What would you call the same structure on a longitudial section?

  1. Cross section = spheroid
  2. Longitudinally = torpedo


Notice the abnormalities within this histo slide of an optic nerve: 

  1. What are the white, empty circles?  
  2. What should be there?  
  3. What would you call the overall process that has occured?

  1. These are dilated axon sheaths
  2. Axons should be here, but they have swelled up and deteriorated
  3. = axonal degeneartion


This is an example of a nerve undergoing axonal degeneration.  The axon has swollen up and retracted back to the cell body.

  1. Based on what you know about wallerian degeneration, what part of the degenerative process is this image illustrating?
  2. What cells are present within the axon sheath?

  1. This image is illustrating macrophages removing the debris left from the degernation of the axon
  2. Microglia


When an axon of a neuron is injured, there is a change that occurs where the Nissl substance is dispersed to the periphery of the cell.

  1. What is this change called?
  2. What type of change is this?  
  3. Is this change reversible or nonreversible?

  1. Central chromatolysis
  2. Sub-lethal change
  3. Reversible


When it comes to demyelination, there is a loss of myelin, but what remains intact?



What are some examples of disease processes that could cause demyelination?

Autoimmune diseases

Canine distemper



  1. What around a nerve produces the connective tissue sheath?
  2. What role does this play in neural trauma?

  1. FIbroblasts
  2. Becuase fibroblasts are involved in the production of the connective tissue sheath, trauma to a nerve can elicit some degree of fibrosis around the nerve


  1. What specific type of trauma is known for causing neural fibrosis?
  2. What problem cam the fibrosis ulimately cause?

  1. Crushing injuries are known for causing fibrosis
  2. The fibrosis can interfere with the ability of the nerve to regrow back through the damaged area


What are the ways in which the PNS responds to injury? (8 ways)


  1. Wallerian degeneration
  2. Central chromatolysis
  3. Demyelination
  4. Neural fibrosis
  5. Neural atrophy
  6. Neuritis
  7. Neuroma
  8. Peripheral nerve sheath tumor


What is polyradiculoneuritis?

Inflammation of the spinal nerve roots


What are the two general causes of neuritis, ganglioneuritis, or polyradiculoneuritis?

Autoimmune mechanism

Infectious agents


  1. What is polyneuritis equi?
  2. Which nerves are most commonly affected?

  1. Polyneuritis equi is an neurological autoimmune disease in horses that causes neuritis, ganglioneuritis, or polyradiculoneuritis
  2. Tends to affect nerves in the cauda equina


What are 2 examples of ascending infectious agents that can enter the body peripherally and ascend into the PNS and CNS?

  1. Rabies
  2. Listeria monocytogenes


How does Listeria monocytogenes most commonly get into the body?

Wounds and lesions, usually in the oral cavity


What might a peripheral nerve sheath tumor be derived from?

Schwann cells




  1. Where on the body might you most commonly encounter a peripheral nerve sheath tumor?
  2. Although these neoplasms can be either malignant or benign, which of the two is more likely?

  1. Subcutis of the limbs  &  Brachial plexus
  2. Benign


A show dog comes in to your clinic with the owner complaining about an odd lump-like nodule on the end of his stumpy tail.  You aspirate the mass for testing and learn that it is non-neoplastic. 

What is one of your differentials associated with the nervous system?


(Non-neoplastic mass due to abnormal regrowth of a nerve)


Explain the process on how a neuroma can develop following neural damage


* Nerve damage * 

-> axon dies back

-> injury cases local fibrosis

-> axon regrows but can NOT reestablish its normal path becuase of the fibrotic tissue now present

-> axon continues to grow regardless

-> balls up

-> forms a NEUROMA


Axonal degeneration in the CNS is similar to what in the PNS?

Wallerian degeneration


Regarding demyelination:

  1. Which cells are being lost in the PNS?
  2. Which cells are being lost in the CNS?

  1. PNS = Schwann cells
  2. CNS = Oligodendrocytes


What are the 2 general forms of demyelination in the CNS?





  1. What is specifically injured in primary CNS demyelination?
  2. What is specially injured in secondary CNS demyelination?

  1. Primary demyelination = injury to the OLIGODENDROCYTES
  2. Secondary demyelination = injury to the AXON & MYELIN SHEATH


  1. What type of disease process might cause primary demyelination in the CNS?
  2. What might cause secondary demyelination?

  1. Autoimmune diseases --> primary demyelination
  2. Inflammation --> secondary demyelination


  1. To review, what is central chromatolysis?
  2. Would you be more likely to observe central chromatolysis earlier in an injurious process or later?

  1. Central chromatolysis is a neural response to injury where the Nissel substance is dispersed to the periphery of the neuronal cell body
  2. Early


  1. What is hydropic degeneration?
  2. Explain indepthly the neural defect/problem that causes this change.

  1. Hydropic degeneration is a swelling due to imparied ion pumps
  2. The cells take in fluid due to an impairment in the ion pumps that maintain equilibrium, particularly between sodium and potassium.  When the ion pumps are impaired, sodium comes into a cells, bringing water with it.  The cell swells.


Is hydropic degeneration a sub-lethal or lethal change?



Explain the difference between apoptosis and necrosis in the CNS.

  1. Apoptosis 
    • Single cell "programmed death"
    • NO inflammation
  2. Necrosis
    • 1 + cells dying in response to injury
    • YES inflammation


Answer the following questions regarding spongiform change in the CNS:

  1. What does TSE stand for?
  2. What causes this disease?
  3. What will form in the neurons?

  1. Transmissible spongiform encephalopathy 
  2. Prions (infectious protien particles)
  3. Vacules will form in neurons


  1. Neural intracellular accumulation of substrates is caused by a deficiency in what?
  2. What is the most common way in which animals get this storage disease?

  1. Enzyme deficiency
  2. Most often inherited 


What is the difference between wallerian/axonal degeneration and demyelination?

Degeneration = breakdown of axon & myelin sheath

Demyelination = breakdown of myelin ONLY


  1. What changes do you notice in this neural tissue?
  2. What would you call this change if it were in the CNS?

  1. Changes present:
    • Dilation of axon sheaths
    • Some swollen axons
    • Some debris
  2. This is called AXONAL DEGENERATION


Describe the changes that have developed in each circled area (within 1 to 2 words):

Blue =

Green =

Yellow = 

Blue = Dilated axon sheath

Green = Debris 

Yellow = Swollen axon


  1. What type of neural change would canine distemper cause?
  2. What type of neural change would toxicosis cause?

  1. Demyelination (Axons are still intact)
  2. Toxicosis = same thing


This is neural tissue from a dog with canine distemper.

What do you call what is circled?


Intranuclear inclusion body

(Characteristic of this virus)


What are 3 characteristics of a necrotic neuron?



+/- pyknotic nuclei



What inflammatory changes would you see with neuronal necrosis?

Phagocytosis by microglial cells


Enlargement of astrocytes


What are 4 causes of neuronal necrosis?

  1. Hypoxia/ischemia
  2. Toxins
  3. Excitotoxins
  4. Viruses


  1. What is the most common cause of neuronal necrosis?
  2. What example of a neural toxin was given?
  3. What examples of excitotoxins were given?

  1. Most common cause = hypoxia/ischemia
  2. Toxins = cyanide, CO
  3. Excitotoxins = glutamate, aspartate, & analogs


True or False:

  1. West Nile and Rabies specifically target neurons.
  2. Viruses like West Nile and Rabies will cause neural necrosis.

If #1 is true, what is a term to describe that attraction? 

  1. TRUE
  2. TRUE
  3. Neurotropism


True or False:

When neurons of the CNS are lost due to necrosis, they can often be replaced.


Lost neurons are not typically replaced


  1. What structure is circled in orange?
  2. What is abnormal about that structure?
  3. What is this change called?

  1. Orange = a neuron
  2. The neuron is (1) shrunken and (2) hypereosinophilic
  3. This is called neural necrosis


  1. What structure is circled in purple?
  2. What change does this structure typically undergo during neuronal necrosis?

  1. Purple = astrocyte
  2. Astrocytes will tend to enlarge during necrosis


What are examples of prion-induced disease in the following animals:

  1. Sheep
  2. Cattle
  3. Elk, deer

  1. Scrapie (sheep)
  2. Bovine spongiform encephalopathy (cattle)
  3. Chronic wasting disease (elk, deer)


  1. Which prion causes TSE?
  2. What change causes this prion to be "bad"?
  3. What does this change make the prion resistant to?

  1. PrPsc - protease resistant prion protein
  2. Normal cellular prion protein (PrPc) becomes mis-folded
  3. This mis-folding inhibits digestion and degradation of the protein, which then accumulates in neurons


Which variant of spongiform encephalopathy is thought to be the result of human infection from cattle with BSE?

Creutzfeldt-Jakob disease


How are transmissible spongiform encephalopathies transmitted?

Oral transmission


  1. Where do TSEs replicate in the body?
  2. How do they get to the CNS?
  3. Which part of the CNS should be sampled on necropsy for TSEs?

  1. Replicate in lymphoid tissue
  2. Get to the CNS by leukocyte traffic or retrograde migration up cranial nerves
  3. Obex should always be sampled!


This is neural tissue from a sheep:

  1. What neural change has occurred at the end of the pointers?
  2. Where specifically do these changes occur?
  3. What is your diagnosis?

  1. Spongiform change (large vacules)
  2. In the neurons
  3. Scrapie


Concerning specific storage diseases, answer the following questions:

  1. Which condition is associated with a deficiency in galactocerebrosidase?
  2. A deficiency in which enzyme causes Beta-Mannosidosi?

  1. Galactocerebrosidosis
  2. Beta-Mannosidase


From studying SO hard, you know that most storage diseases are inherited; however, I want to talk about Swainsonine, an acquired storage disease.

  1. What plant causes this specific storage disease?
  2. What enxyme does this inhibit?

  1. Swainosonine is a toxic alkaloid in Locoweeds
  2. This inhibits alpha mannosidase  


  1. What neural change has occurred at the end of the arrows?
  2. What disease process causes this?

  1. Swollen neurons
  2. Lysosomal storage diseases cause this


Which type of parenchymal swelling in the CNS is typically associated with an inflammatory process?

Increased vascular permeability


What 3 changes can cause parenchymal swelling of the CNS?

Cytotoxic edema

Increased vascular permeability (associated with inflammation)



What are 3 causes of hemorrhage in the CNS?





  1. In which 2 general parts of the CNS might hemorrhage develop?
  2. Hemorrhage is toxic to the neuropil, leading to what progressive changes?
  3. What is progressive hemorrhage of the spinal cord called?

  1. Subdural and in the parenchyma
  2. Progressive hemorrhage & necrosis
  3. Hematomyelia


This is part of the spinal cord:

  1. What do you call the progressive change that has occurred?
  2. What's another term for this condition?

1.  Hematomyelia

(Definition: progressive hemorrhage of the spinal cord)

2.  Hemorrhagic myelomalacia


This is a histologic slide of a spinal cord:

What term(s) do you use for the change depicted at the end of the blue arrow?


(AKA hemorrhagic myelomacia)


This is neural tissue from a dog.

  1. List 2 abnormalities.
  2. What is this condition called?

  1. Hemorrhage & dilated axon sheaths
  2. Hematomyelia 


This is an image of the dorsal brain:

What would you call this?


Subdural hemorrhage


  1. With hemorrhage in the leptomeninges, what type of tissue tends to build up?
  2. The change being referred to can lead to adhesions, which can then lead to what?

  1. Fibrous tissue
  2. Seizure activity


Where is subdural hemorrhage located?

Beneath the dura mater


What can cause subdural hemorrhage?

Rupture of veins or arteries within the leptomeninges due to trauma such as being whacked on the head


What are 2 general causes of malformations of the CNS?

  1. Genetic defects
  2. Injury to the brain/spinal cord during development
    • In utero viral infection
      • BVD
    • Toxins/poisonous plants eaten by the dam


  1. What is hydrocephalus?
  2. What causes internal hydrocephalus?
  3. What causes external hydrocelphalus?

  1. Hydrocephalus : dilation of the ventricular system of the brain in association with accumulation of CSF
  2. Internal hydrocephalus : obstruction of the ventricular system
  3. External hydrocephalus : failure to absorb CSF by arachnoid villi


Which is most common, internal or external hydrocephalus?

Internal hydrocephalus


True or False:

  1. Hydranencephaly is a CSF-filled cavity within the neuropil of the brain.
  2. The cavity formed within the neurophil of the brain is lined by ependymal cells.

  1. TRUE
  2. FALSE

Hydranencephaly : a CSF-filled cavity within the neurophil of the brain, NOT lined by ependyma