Diseases of the Brain

Question 1

Microglia

Answer 1

Phagocytosis, Ag presentation, chemokine & cytokine production, control of BBB
Originate from yolk sac blood islands

Question 2

Astrocytes

Answer 2

BBB control, leukocyte recruitment, gliossi, cytokine & neutrophin production, AG presentation

Question 3

Structure of the BBB

Answer 3

Endothelial cell lining with tight junctions
Endothelial & parenchymal basemement membrane
Pericytes
Glia limitans formed by astrocyte processes linked by gap junctions
Microglial cells & other APCs

Question 4

Pathways over the BBB

Answer 4

Paracellular aqueous, transcellular lipophilic, transport proteins, transcytosis

Question 5

Adhesion molecules of the BBB

Answer 5

Selectins: Bind carbohydrates, initiate leukocyte-endothelial interaction
Integrins: Bind to cell-adhesion molecules & ECM, strong adhesions
Ig-superfamily: Roles in cell adhesion, ligand for integrins

Question 6

Multiple sclerosis

Answer 6

= Chronic inflammatory demyelinating disease of the CNS –> T cell autoimmune disease
Relapse-remitting course leading to secondary progression

Question 7

Pathophysiology of MS

Answer 7

Early: Leakage of BBB –> Immune cell infiltration & inflammatory demyelination
Late: Glia limitans damage & astrocyte dysfunction –> ROS production –> Metabolic stress & energy deficiency
Neuro-axonal & oligodendrocyte damage & cell death
Neurodegenerative process promote further damage at distal sites

Question 8

NMOSD

Answer 8

IgG auto-antibodies against AQP-4 –> Astrocyte loss (primary) & secondary damage to axon and oligodendrocytes

Question 9

Parkinsons Disease

Answer 9

alpha-synuclein deposits hamper neuron function and lead to cell death in the substantia nigra pars compacta (Less dopaminergic neurons)

Question 10

Ischemic stroke

Answer 10

Infarction of the brain, spinal cord or retina –> Hypoxemia

Question 11

Pathophysiology of Stroke

Answer 11

Clot –> Less cerebral blood flow –> Hypoxia-ischemia & lack of O2 and glucose –> Mismatch between energy requirements & availability –> Excess excitatory AAs –> mGlur or NMDAR activation –> Excess Ca2+ neurons
ROS & free radical production –> Apoptosis
Astrocytes & Oligos: Trophic factor release
Microglia: Inflammatory response –> BBB dysfunction

Question 12

Beta-Amyloid in Alzheimers Disease

Answer 12

Aggregates deposed in brain over years –> Cell death
Precursor protein cut by alpha secretase = good, cut by beta/gamma secretase = bad
Might be due to zink, copper, apolipoprotein E4 and low pH

Question 13

Tau in Alzheimers Disease

Answer 13

Hyperphosphorylation & aggregation in neurofibrillary tangles –> No more transport –> Cell death