L7 Neurovascular Interactions in Developing Brain Flashcards
3 barriers in the brain
- Meninges (outermost barrier) - dura mater, arachnoid mater, pia mater
- BBB
- Blood-CSF barrier
What is the neurovascular unit composed of?
neurons, astrocytes, endothelial cells of BBB, myocytes, pericytes, ECM components
BBB features
- NVU
- tight junctions (no paracellular transport)
- non-fenestrated
- very low rates of transcytosis
- selectively permeable to key nutrients
- lipophilic molecules can cross
Molecular guidance cues that guide both endothelial cells and axons
Angioneurins e.g. VEGF, Netrin, Ephrin, Robo4
True or False: Initially, the neural tube is avascular
True
What gives rise to the neural tube?
invagination in ectoderm
What are recruited by the neural tube to form the perineural vascular plexus (PNVP)?
Endothelial cell precursors (angioblasts) from adjacent presomitic mesoderm
The PNVP promotes __ of the neural tube
vasculogenesis
What is the difference between vasculogenesis and angiogenesis?
Vasculogenesis is the formation of blood vessels de novo, whereas angiogenesis is the formation of blood vessels from pre-existing blood vessels
Angiogenic sprouts from PNVP ingress radially from the basal surface of neural tube towards its apical surface to form…
the intraneural vascular plexus (INVP)
NPCs secrete __ when they become hypoxic to recruit endothelial cells to the surface of the neural tube
VEGF-A
__ signalling is required for blood vessel ingression
VEGF-A and Wnt7 signalling
Blood vessels are important for vascular-guided migration of __
GABAergic interneurons
In a poorly vascularised and hypoxic environment, RGCs express __ , which triggers glycolysis and RGC proliferation.
HIF1α (transcription factor)
Vascularisation relieves hypoxic conditions. How does this affect RGCs?
RGCs begin to differentiate more (via asymmetric division, following HIF1α degradation)
Are astrocytes present in embryonic stages?
No
What cell type is present in embryonic stages to facilitate BBB development?
Pericyte
Describe NVU maturation
- 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
During development, oligodendrocyte precursors migrate dorsally from … to homogeneously populate the CNS
their birthplace (VZ brain and spinal cord)
How are OLPs guided?
by the vasculature
OLP-secreted Wnt acts in an autocrine manner to induce expression of __
CXCR4
Endothelial cells secrete __ to attract OLPs and sustain their undifferentiated state
CXCL12 (CXCR4 ligand)
Maturation of oligodendrocytes is accompanied by…
downregulation of Wnt expression, as well as CXCR4 in OLPs and concomitant OLP detachment from the vasculature
During postnatal development, new neurons are continuously generated in the __
sub-ventricular zone
Vasculature formation and structural organisation in the rostral migratory stream is orchestrated by __
astrocytes
How does angiogenesis promote NSC differentiation (Lange et al., 2016)?
by targeting glycolysis
In the study by Lange et al. (2016), how does suppression of brain angiogenesis affect neurogenesis?
it suppresses neurogenesis
In the study by Lange et al. (2016), reduced levels of HIF1α lead to…
reduced proliferation and increased differentiation of neural stem cells
