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NMH: Module 2 > MS Pathology and Animal Models > Flashcards

Flashcards in MS Pathology and Animal Models Deck (21)
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Macro and micro MS pathology?

Atrophy: big ventricles, wide sulci

WM demyelin
GM demyelin

inflam -> demylein-> axonal loss -> neurodegen

Commonly at optic nerve, midbrain (SNpc->PD), pons (fatal), cerebellum (ataxia) , s.cord


Main cell involved in the destruction of myelin in MS



Presence of macrophages are useful for identifying what in MS pathology?

The edge of the lesion


Stains for MS?

Luxol Fast-blue

Oil Red: old lesion- the myelin has oxidised due to free radicals


Explain why oligoclonal bands are present in MS

These are very specific antibodies (normally you should have a very varied repertoire)

NB: These antibodies are usually against myelin


How MS causes progressive neurodegeneration?

- Axonal damage/loss -> neuronal loss [upstream effect] and synapse degradation [downstream] ]- because there is no propagation of action potentials

- Myelin loss -> axon isn’t protected -> increased Na+ channel expression (normally inhibited by myelin} -> more Na+ inside axon -> ionic imbalance -> can’t produce ATP -> ATP exhaustion -> metabolic problems

- Ca2+ getting in (whilst we try to get Na+ out of the axon) -> calcium-dependent pathways e.g. calpain -> cell death


Relationship between axonal loss and severity of MS symptoms

More axonal loss = more severe symptoms


Features of pathological axons in MS?

APP deposition and end bulbs


Features of white matter inflammation VS grey matter inflammation

White matter: mainly perivascular in parenchyma; T and B cells

Grey matter: infiltration mainly in the meninges; less T and B cells


In grey matter inflammation, what structures surround the lesions?

Lymphoid follicles


Relationship between lymphoid follicles and grey matter degeneration?

More lymphoid follicles seem to be associated with a greater loss of neurons and a worse progression of the disease

TLS -> meningeal inflammation -> GM pathology

Meningeal inflammation -> more cortical pathology, disease progression, total demyelination, activated microglia, pro-infl chemokines


Main animal models in use for MS?

- Experimental Autoimmune Encephalomyelitis (EAE)
- Theiler’s Murine Encephalomyelitis Virus (TMEV)
- Cuprizone-induced MS
- Lysolecithin-induced MS


Describe Experimental Autoimmune Encephalomyelitis (EAE)

- Generation of myelin-specific autoimmune T cells.
Immunisation of animals (rodents, primates) with myelin antigens in adjuvant.
- CD4+ T cells.
- Th17 and Th1.
- Depending on antigen used and mouse/rat strain we have different models of MS


Describe passive Experimental Autoimmune Encephalomyelitis (EAE)

transfer of myelin-specific T cells into WT/Rag-/- mice

RAG = recombination activation gene


Evaluate how useful Experimental Autoimmune Encephalomyelitis (EAE) is as a model for MS

Good model to study autoimmunity, not so much MS

Short- no remyelination
No relapses
Mainly white matter


Describe Theiler's Murine Encephalomyelitis Virus (TMEV)

- a virus used in mouse models of MS as it induces virally induced paralysis and encephalomyelitis

- axonal damage precedes demyelination (opposite to EAE/MS)

infection -> neurodegradation -> inflammation -> demyelination -> axonal/neuron loss


Describe cuprizone

It is a copper chelator

-> oligodendrocyte cell death -> demyelination
-> activation of astrocytes and microglia -> inflammation


Describe the events following cuprizone removal

OPCs -> new oligodendrocytes -> remyelination (this happens after cuprizone removal)


Describe the advantages of using cuprizone as a model for MS

Good model for demyelination and remyelination

(possibly good for studying mitochondrial dysfunction in MS)


Describe lysolecithin

- Activates phospholipase A2
- direct toxicity to myelin sheath (lipid degradation) -> rapid neuronal demyelination w/ intact oligodendrocytes
- no axonal damage
- leukocyte infiltration in demyelinated areas -> repair?


Evaluate the use of lysolecithin as a model for MS

Better on young animal, showing complete remyelination after 5-6 weeks

Best model used to study remyelination and the role of the immune system in repair