Chapter 28: CNS

Question 1

What is selective vulnerability?

Answer 1

The fact that different neurons posses different fucntions, protein, environments etc which makes them vulnerable to different pathogenic mechanisms.

Question 2

What is gliosis?

Answer 2

Hypertrophy and hyperplasia of astrocytes. Nucleus changes from pale, to big with distinct nucleoli. Becomes gemistocytic astrocytes.

Question 3

How does microglia respond to injury?

Answer 3

1) proliferate
2) developing elongatedd nuclei
3) formin aggregates around small areas of necrosis
4) congregating around cell bodies of dying neurons

Question 4

Two major categories of cerebravascular diseases:

Answer 4

1) Ischemic

2) Hemorrhagic

Question 5

What is global cerebral ischemia?

Answer 5

Reduced blood flow to the entire brain as a product of hypotension, shock or cardiac arrest.

Question 6

What is focal cerebral ischemia?

Answer 6

reducedd blood flow to a localized area. Can be through:

1) embolism most often from heart
2) Thrombotic occlusions
3) inflammatory processes may give lumen narrowing

Question 7

Different forms of prion proteins:

Answer 7

1) PRPc = the normal form

2) PRPsc ) th abnormal beta sheeted form

Question 8

What is the pathological background of MS?

Answer 8

Immune response targeting components of the myelin sheath. Mainly:

1) Th1 which secretes IFN-gamma and recruits macrophages
2) Th17 which recruits leukocytes

Damage down to leukocytes (mainly t-cells CD4 (also CD8 but not as many) and macrophages)

Question 9

What does sclerosis mean?

Answer 9

Hardening

Question 10

NMO?

Answer 10

Neuromyelitis optica - bilateral optic neuritis and spinal cord demyelination. Antibodies against aquaporin 4 - the major aquaporin in astrocytes - leading to astrocyte injury.

Question 11

Acute disseminated encephalomyelitis

Answer 11

After infections myelin is removed up to 20 % die rest full recovery.

Question 12

What is an neurodegenerative disease?

Answer 12

Characterized by loss of neurons. Most commonly characterized by presence of protein aggregates.

Question 13

FTLD?

Answer 13

Frontotemporal lobar degeneration. Focal degeneration of frontal or temporal lobes. Has tau or TDP43 (a RNA binding protein) cellular inclusions.

Question 14

What is the cause of parkinson?

Answer 14

Loss of dopaminergic neurons from the substansia nigra leading to dysfuntion in the extrapyrimidal circuitry.

Question 15

Genes invloved in PD:

Answer 15

1) alpha-synuclein - lipid binding protein in the synapses.
2) mitochondrial dysfuntion - parkin, pink-1 and DJ-1. DJ-1 = transcription factor that localises to Mitochondria in ox. stress. Pink-1(kinase)+parkin (E3) degrades dysfuntional mitochondria.

Question 16

What is the cause of huntington disease?

Answer 16

death of striatal neurons. This is due to mutation in huntingtin. Repeat number in beginning of protein.

Question 17

What causes ALS?

Answer 17

Loss of motor neurons in cerebral cortex and lower motor neurons in brain stem and spinal cord. A lot of genes - SOD1 in about 20 %.

Question 18

Name some common gliomas:

Answer 18

1) astrocytoma
2) oligodendrogliomas
3) ependyoma

Question 19

Astrocytomas classification:

Answer 19

Divided into 2: Infiltrating and pilocytic

Question 20

Infiltrating astrocytomas:

Answer 20

Subdivided into 4 classes:

1) classic - Rb, p53, PTEN mutations.
2) proneural - p53 and isocitrate dehydrogenase (IDH1 +2)
3) neural
4) mesenchymal

generally charaterised by evasion of growth supression and sustained proliferative signal.

Question 21

Pilocytic astrocytomas:

Answer 21

Relatively benign

Question 22

Oligodendroglioma

Answer 22

Most common mutation IDH 1 +2.