CNS2 Flashcards
Neuronal injuries affecting axons (axonopathies) - list three
Wallerian degeneration; proximal axenopathy; distal axonopathy
Neuronal injuries affecting the cell body of the neuron - list three
Central chomatolysis; inclusions; neuronal necrosis and its resolution (differs from pannecrosis)
Some conditions affecting the neuron can affect only the axon, and are at least theoretically reversible. True or False.
True - If you have axonal injury you have some hope for regeneration - neurons will try to regenerate their processes
Wallerian Degeneration is the most common axonopathy in vet med. True or False.
True
Wallerian degeneration follows ____ or ____ axonal transection/separation) in PNS or CNS.
Physical or functional
Wallerian Degeneration –> ___ and ____ degeneration together.
Axon and myelin
What is the first step (can occur within minutes) in Wallerian Degeneration? (following trauma vs. ischemia secondary to compression)
Cytoskeletal degeneration in the axon; microfilaments fall apart; in trauma = dephosphorylation of neurofilament arms; in ischemia secondary to compression = ATP reduction –> leads to a transport blockade
In Wallerian Degeneration, cytoskeletal degeneration in the axon leads to ______ of axon ____.
Denaturation of axon proteins
Wallerian degeneration (PNS) - in 24 hours, what is the finding?
Tissue collapse
Wallerian degeneration (PNS) - in 2-10 days, what is the finding?
Phagocytosis of debris; muscle atrophy; attempted regeneration (neuron shifts from making synaptic vesicles to structural parts of the axon - and sends it down to the ends of the axon and starts proliferating axonal processes - axonal sheath is a good thing because you can’t get lost)
Wallerian degeneration (PNS) - in 2-3 weeks, what is the finding?
Remyelination with altered length between nodes if successful; Bungner’s bands and chronic atrophy if unsuccessful
Motor neurons start to make what growth factor that serves as a stimulus for axonal growth in motor neurons?
NGF - neuronal growth factor
If regeneration is successful, we get ____ atrophy.
Reversed
If regeneration is unsuccessful, we get ____ atrophy of distal nerve and muscle and _____ formation.
permanent; neuroma
What factors determine whether WD is repaired successfully?
Depends on success of axon regeneration - how well the proximal and distal ends of nerves are aligned; whether PNS vs CNS is involved; how close the transection is to the cell body
Where is regeneration more likely to occur, PNS or CNS and why?
PNS because PNS has a basement membrane - no BM in CNS
Brachial plexus avulsion (trauma-driven Wallerian degeneration in PNS)
Trauma drives the limb caudally along the body, pulls the spinal nerves away from the cord at vertebral foramina, first ventrally, then dorsally
Bunger’s bands are indication of successful resolution of WD and return of function. True or False.
False
A short time after brachial plexus avulsion (days) you could detect microscopic degeneration or loss of axons and myelin, and muscle atrophy. True of False.
True
Lesions associated with spinal cord compression: WD caused by ischemia –> most WD affects ____ funiculi most severely.
Ventral
Lesions associated with spinal cord compression: WD caused by ischemia: describe lesions listed in increasing severeity
With moderate ventral compression, ventral white tracts degenerate; Wallerian degeneration of lateral then dorsal funiculi as compression is more severe; Malacia of gray matter
Not all injuries will involve all funiculi at the site of compression. True or False.
True
When WD affects the spinal cord after a compressive insult, it is primarily a result of which process? Thrombosis, severed nerve roots, ischemia, inflammation?
Ischemia
What area of the cord would be affected first if compression occurred on the dorsal surface instead of ventrally?
Sensory
In “watershed lesions” of severe Wallerian Degeneration; posterior tot he site of greatest injury, what degenerates?
Ventral white tracts
In “watershed lesions” of severe Wallerian degeneration; cephalic to the site of injury, what degenerates?
Dorsal white tracts degenerate
Both posterior to the site of greatest injury and cepahlic to the site of injury in watershed lesions of severe Wallerian degeneration; cause axons distal to the cell body to degenerate, starting at the point of injury. True or False.
True
If a relatively mild ventral spinal cord compression causes WD limited to the ventral cord at TL, what lesion would be present in the dorsal white matter?
WD would not be present in dorsal white matter.
Type I intervetebral disk diseases causing WD
Occurs in old dogs; cervical; annulus fibrosis degenerates, protrusion
Type II intervertebral disk disease causing Wd
Occurs in chondrodystrophic dogs; T-L junction; nucleus pulposis degenerates; extrusion; multiple discs affected in 25% of affected Dachshunds
What is more severe, type I or type II intervetebral disk disease?
Type II
Equine cervical instability:
recurrent transietn deformation with vertebral over-riding
Equine vertebral affects young, growing male horses. specifically these breeds:
TB, TW, WB
Throwback, tenessee walker, warm blood
Equine vertebral instability affects which cervical vertebra?
C3-4, 5-6, 6-7
Equine vertebral instability –> _____ joint pathology
intervertebral
Canine Vertebral malformation –> instability has breed predispositions, true or false?
True
Dobermans have ___ compression of the cord in canine vertebral malformation.
Dorsal
Static stenosis does not occur in canine vertebral malformation. True or False.
False –> static stenosis can occur but is less common, and it can also affect horses
Diskspondylosis, epidural abscess, vertebral malformation, neopasltic metastases, and fracture/luxation all can cause _____ in the spinal cord.
Wallerian degeneration
Wallerian degeneration –> failure of ___ transport.
fast ortho-grade transport
Proximal axonopathy –> failure of ___
slow ortho-grade transport
Distal axonopathy –> failure of
retrograde (anterograde) transport
Equine degenerative myeloencephalopathy proximal axonopathy: natural disease
Proximal axonoapthy; altered proprioception; lots of species affected; inherited/acquired vitamin E deficiency/aging
Equine Laryngeal Hemiplegia - A distal axonopathy –> lesions
Distal axonoapthy; distal axonal degeneration from the ends of longest nerves: left recurrent laryngeal nerve and others; herediatry tendency
What distinguishes Wallerian degeneration from other axonopathies?
Morphologic answer: Simultaneous degeneration of axon and myelin
Injuries to the cell body: central chromatolysis
nonspecific reaction to injury to a living cell body reflects change; such cells frequently lose synaptic contact with neighbors; loss of Nissl substance is visible 2d - 6 wks after injury
List different types of neuronal inclusions:
Secondary lysosomes in storage diseases; viral inclusions (not every one - DNA viruses - nuclear; RNA viruses - cytoplasmia); Insoluble products of proteosomal degradation - unfolded protein response and cell death (some are specific to certain diseases like AD, PD, prions); Other cell types can ALSO have inclusions
RNA viruses usually have inclusions at what location in the cell?
Cytoplasm (exception - canine distemper has intranuclear viral inclusions)
Acute, neuronal necrosis
Red is dead, pyknosis; can be selective and/or localized (depends on cause); followed by neuronophogia
Neuronal necrosis by itself results in _______ microscopically, and results grossly in brain ____.
neuronal loss; brain atrophy
In temporal sequence, what is the correct order of microscopic events following neuronal necrosis?
neuronal necrosis –> Neuronophagia –> neuronal loss –> brain atrophy
Why do neurons die after ischemia?
Increased glutamate release from ischemic excitatory neurons –> astrocyte detox (glu –> gln) is disabled; Glutamate binding to susceptible dendrites –> dysfunctional ion pumps –> cytosoloic flodding by Ca2+ –> lactic acidosis, cell swelling; location varies with insult
In slow, incremental neuronal degeneration and loss, do we see any acute changes?
NO
Motor neuron disease - how is it determined?
genetically or idiopathically –> results in loss of previously “normal” neurons (denegeration of spinal motor neurons) - and may occur over a long period
Cerebellar abiotrophy
primary degeneration/loss of purkinje cells, and sometimes neurons in other areas (multisystem atrophy). Very orderly in a given group of patients, very different between them
The time course of purkinje cell loss is similar in all cerebellar abiotrophies. True or False.
False
Spinal Muscular atrophy is a motor neuron disease that is caused by what?
Genetically determined or idiopathic degeneration of spinal motor neurons
In spinal muscular atrophy, what enzyme is dysfunctional? what is deficient?
Superoxide dismutase dysfunction; cytoskeletal deficiency, vitamin E deficiency
How can you treat spinal muscular atrophy in horses?
You can treat with vitamin E, which will stop it from progressing, but won’t fix it
Oligodendrocyte/Schwann cell injury results in…
demyelinination - primary destruction of the myelin sheath
demyelination from oligodendrocyte/schwann cell injury is due to ______
attack on myelin heath and death of parent cell
Demyelination can be a random event. True or False.
True
Demyelination affects _____ (longest or shortest) fibers most severely because ____
longest - because they have the most affected segments
Demyelination can be focal and severe. True or False.
True
Describe gross lesions of demyelination
Gross lesions are discoloration of the white matter and may not be grossly vissible.
Microscopic appearance of demyelination
there is a special stain for myelin, and loss of this stain shows areas of demyelination
Three mechanisms of demyelination
(1) Oligodendrocyte lysis/death - due to viral, chemical or nutritional causes
(2) Inflammatory attack on myelin sheat - due to viral, or autoallergic
(3) Chemical damage to myelin sheath - due to chemical or metabolic causes
Central Pontine Myelinolysis is demyelination due to what?
demyelination due to oligodendrocyte death
Coonhound paralysis is inflammatory demyelination of ….
ventral roots, affecting peripheral and cranial nerves
Coonhound paralysis is caused by?
coonhounds eating raccoons
Experimental allergic encephalitis, experimental allergic neuritis, and multiple sclerosis are all examples of ______ demyelination.
autoimmune
Repair of myelin sheath injury (remyelination) is more effective in PNS or CNS? why?
PNS - schwann cells divide rapidly and there is a 1:1 relationship with axon; in the CNS oligodendrocytes can proliferate but there is only one oligodendrocyte per several axons, and no basement membrane for guidance; and seondary axonal loss makes damage permanent
What makes demyelination permanent in the CNS?
secondary axonal loss
Two astrocytic reactions to injury:
hypertrophy and hyperplasia
Two types of astrocyte hypertrophy are?
fibrillary and gemistocytic
Describe fibrillary astrocyte hypertrophy
increase in cell processes with more GFAP +/- vimentin; enlarged nuclei with HE
Describe gemistocytic astrocyte hypertrophy
swollen, reactive astrocytes
What is astrogliosis
diffuse increase in number of processes and number of cells present mixed with surivivng normal cells
Astroglial scars are partly derived from stem cells and consito f what?
nothing but astrocytes - occurs at edge of severe injury - resident astrocytes normally remain at the periphery of an astroglial scar and new astrocytes that have migrated as precursors from near the ventricles form the center of the scar
Why are microglial cells called rod cells?
they have elongated nuclei
Brain macrophages have readily visible cytoplasm. True or False.
True.
Microglia develop activated phenotype and with cell death become ____
macrophages
Perivsacluar cuffs
cytokine-stimulated influx of microglia after injury
gitter cells
active phagocytosis of microglial cells in tissue
In meninges and PNS, external _____ influx occurs after injury.
Macrophage
Can you see perivascular brain macrophgaes and microglia in the brain?
Yes
