L7 Neurovascular Interactions in Developing Brain

Question 1

3 barriers in the brain

Answer 1

1. Meninges (outermost barrier) - dura mater, arachnoid mater, pia mater
2. BBB
3. Blood-CSF barrier

Question 2

What is the neurovascular unit composed of?

Answer 2

neurons, astrocytes, endothelial cells of BBB, myocytes, pericytes, ECM components

Question 3

BBB features

Answer 3

• NVU
• tight junctions (no paracellular transport)
• non-fenestrated
• very low rates of transcytosis
• selectively permeable to key nutrients
• lipophilic molecules can cross

Question 4

Molecular guidance cues that guide both endothelial cells and axons

Answer 4

Angioneurins e.g. VEGF, Netrin, Ephrin, Robo4

Question 5

True or False: Initially, the neural tube is avascular

Answer 5

True

Question 6

What gives rise to the neural tube?

Answer 6

invagination in ectoderm

Question 7

What are recruited by the neural tube to form the perineural vascular plexus (PNVP)?

Answer 7

Endothelial cell precursors (angioblasts) from adjacent presomitic mesoderm

Question 8

The PNVP promotes __ of the neural tube

Answer 8

vasculogenesis

Question 9

What is the difference between vasculogenesis and angiogenesis?

Answer 9

Vasculogenesis is the formation of blood vessels de novo, whereas angiogenesis is the formation of blood vessels from pre-existing blood vessels

Question 10

Angiogenic sprouts from PNVP ingress radially from the basal surface of neural tube towards its apical surface to form…

Answer 10

the intraneural vascular plexus (INVP)

Question 11

NPCs secrete __ when they become hypoxic to recruit endothelial cells to the surface of the neural tube

Answer 11

VEGF-A

Question 12

__ signalling is required for blood vessel ingression

Answer 12

VEGF-A and Wnt7 signalling

Question 13

Blood vessels are important for vascular-guided migration of __

Answer 13

GABAergic interneurons

Question 14

In a poorly vascularised and hypoxic environment, RGCs express __ , which triggers glycolysis and RGC proliferation.

Answer 14

HIF1α (transcription factor)

Question 15

Vascularisation relieves hypoxic conditions. How does this affect RGCs?

Answer 15

RGCs begin to differentiate more (via asymmetric division, following HIF1α degradation)

Question 16

Are astrocytes present in embryonic stages?

Answer 16

No

Question 17

What cell type is present in embryonic stages to facilitate BBB development?

Answer 17

Pericyte

Question 18

Describe NVU maturation

Answer 18

• Wnt/β-catenin signalling (neurons to ECs, development of BBB properties)
• ECs secrete PDGF-BB, which interacts with PDGF-β in pericytes → pericyte recruitment
• Astrocytes secrete Shh, which acts on PTC-1 → BBB formation
• ECs secrete VEGF & IGF-1 → adequate neurovascular patterning

Question 19

During development, oligodendrocyte precursors migrate dorsally from … to homogeneously populate the CNS

Answer 19

their birthplace (VZ brain and spinal cord)

Question 20

How are OLPs guided?

Answer 20

by the vasculature

Question 21

OLP-secreted Wnt acts in an autocrine manner to induce expression of __

Answer 21

CXCR4

Question 22

Endothelial cells secrete __ to attract OLPs and sustain their undifferentiated state

Answer 22

CXCL12 (CXCR4 ligand)

Question 23

Maturation of oligodendrocytes is accompanied by…

Answer 23

downregulation of Wnt expression, as well as CXCR4 in OLPs and concomitant OLP detachment from the vasculature

Question 24

During postnatal development, new neurons are continuously generated in the __

Answer 24

sub-ventricular zone

Question 25

Vasculature formation and structural organisation in the rostral migratory stream is orchestrated by __

Answer 25

astrocytes

Question 26

How does angiogenesis promote NSC differentiation (Lange et al., 2016)?

Answer 26

by targeting glycolysis

Question 27

In the study by Lange et al. (2016), how does suppression of brain angiogenesis affect neurogenesis?

Answer 27

it suppresses neurogenesis

Question 28

In the study by Lange et al. (2016), reduced levels of HIF1α lead to…

Answer 28

reduced proliferation and increased differentiation of neural stem cells