Neuroinflammation and Neurodegeneration

Question 1

_________________ placed heterotopically in the __________ and into the ___________ of the rabbits survive for prolonged, sometimes indefinite, periods of time.

Answer 1

allogeneic skin grafts, anterior chamber of the eye, brains

Question 2

What is an allogeneic graft?

Answer 2

graft derived from a different donor of the SAME SPECIES

Question 3

What is a syngeneic graft?

Answer 3

graft derived from a genetically identical individual (e.g. identical twin)

Question 4

What is a xenogeneic graft?

Answer 4

graft derived from a DIFFERENT SPECIES

Question 5

What is an autologous graft?

Answer 5

graft derived from the SAME INDIVIDUAL

Question 6

What is a heterotopic graft?

Answer 6

graft placed in a NON PHYSIOLOGICAL SITE (e.g. skin transplanted into the brain)

Question 7

What are some immune privileged sites?

Answer 7

• eye (cornea, anterior chamber, vitreous cavity, subretinal space)
• brain (ventricles and striatum)
• pregnant uterus
• ovary
• testis
• adrenal cortex
• hair follicles

Question 8

What is the function of the BBB?

Answer 8

create resistance to anything coming from the outside

Question 9

TRUE or FALSE: the adaptive immune system is the first line of defense

Answer 9

FALSE: innate is first line

Question 10

TRUE or FALSE: the adaptive immune system is characterized by memory

Answer 10

TRUE

Question 11

What are the innate immune system cells?

Answer 11

• macrophages
• neutrophils
• NK cells
• mast cells
• basophils
  -eosinophils
• dendritic cells
• microglia
• astrocytes

Question 12

What are the adaptive immune system cells?

Answer 12

• T cells
• B cells
• dendritic cells
• microglia
• astrocytes

Question 13

Is CNS inflammation an innate or adaptive response>?

Answer 13

innate

Question 14

What happens to the shape of astrocytes when they are activated?

Answer 14

they become narrow (normally wide and flat)

Question 15

_______________ ______________ is one of the most common and earliest features of nearly all neuroinflammatory disorders.

Answer 15

microglial activation

Question 16

In vitro assays of microglial function have conclusively demonstrated their ability to acquire _____________ or ____________ functions. (What does this mean?)

Answer 16

neuroprotective; neurotoxic (i.e. microglia are both pro- and anti-inflammatory)

Question 17

What are the functions of microglia and macrophages within the CNS?

Answer 17

• pruning synapses during development
• work with complement proteins (label synapses that need to be removed)
• monitor neuronal activity/environment
• clean up lesion/dead tissue during pathology

Question 18

What are microglia functions during CNS injury?

Answer 18

• phagocytosis of synapses
• activate astrocytes
• remyelination

Question 19

What is the most important step for activating microglia?

Answer 19

priming

Question 20

TRUE or FALSE: alert state microglia can become pathological

Answer 20

TRUE

Question 21

___________ ____________ keep microglial in a down-regulated state.

Answer 21

neuron-glial interactions

Question 22

TRUE or FALSE: younger age promotes alert state of microglia

Answer 22

FALSE: promotion of alert state increases with age

Question 23

TRUE or FALSE: While M1 microglia are more anti-inflammatory, M2 are more pro-inflammatory

Answer 23

FALSE: M1 is pro, M2 is anti-inflammatory

Question 24

What is the relationship betwen microglial activation and neuronal degeneration?

Answer 24

bidirectional (see slide 20 diagram)

Question 25

TRUE or FALSE: thickness of the corpus callosum is increased in MS.

Answer 25

FALSE: decreased

Question 26

Is MS a neurodegenerative disease?

Answer 26

yes

Question 27

What are the characteristics of a neurodegenerative disease?

Answer 27

- affect specific parts of functional systems in nervous system - begin insidiously, after long period of normal function with gradual progression - CSF shows minimal changes (mild increase in proteins) - imaging shows either no change or only a volumetric reduction (atrophy)

Question 28

TRUE or FALSE: HLA genetic mutation is specific to MS

Answer 28

FALSE: connected with immune response in general

Question 29

TRUE or FALSE: in MS, neuronal degeneration from mitochorndrial injury, oxidative stress, and ionic imbalance will continue even WITHOUT inflammation

Answer 29

TRUE

Question 30

TRUE or FALSE: MS is a progressive disease

Answer 30

TRUE

Question 31

Describe the inside-out hypothesis of neurodegeneration in MS.

Answer 31

- WM pathology: demyelination --> axonal degeneration - GM pathology: axonal degeneration --> demyelination (inside out) - MS could occur due to one or the other, or both

Question 32

What is the role of autophagy in neurodegeneration?

Answer 32

triggers inflammation

Question 33

What is the ER normally responsible for? What does pathology cause?

Answer 33

- normal: synthesis of proteins - path: misfolded proteins

Question 34

What are the mechanisms activated in the ER with pathology?

Answer 34

- apoptosis - inflammation

Question 35

what are the priming factors fro ER stress in AD? What can these lead to?

Answer 35

- metabolic syndrome - depression - aging - TBI - infection - can lead to neuroinflammation