MS Pathology and Animal Models Flashcards Preview

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

Flashcards in MS Pathology and Animal Models Deck (21)
Loading flashcards...
1

Macro and micro MS pathology?

Atrophy: big ventricles, wide sulci

WM demyelin
GM demyelin
Remeyelin

inflam -> demylein-> axonal loss -> neurodegen

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

2

Main cell involved in the destruction of myelin in MS

Macrophages

3

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

The edge of the lesion

4

Stains for MS?

Luxol Fast-blue

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

5

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

6

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

7

Relationship between axonal loss and severity of MS symptoms

More axonal loss = more severe symptoms

8

Features of pathological axons in MS?

APP deposition and end bulbs

9

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

10

In grey matter inflammation, what structures surround the lesions?

Lymphoid follicles

11

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

12

Main animal models in use for MS?

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

13

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

14

Describe passive Experimental Autoimmune Encephalomyelitis (EAE)

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

RAG = recombination activation gene

15

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

16

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

17

Describe cuprizone

It is a copper chelator

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

18

Describe the events following cuprizone removal

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

19

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)

20

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?

21

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