Vessel maturation schedule determines vulnerability to neuronal injuries of prematurity

Licht, Tamar; Dor-Wollman, Talia; Ben-Zvi, Ayal; Rothe, Gadiel

doi:10.1172/jci79401

Cited by 33 publications

(40 citation statements)

References 35 publications

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“…This unique vascular orientation is dictated in the postnatal brain via astrocyte-derived VEGF signaling as evidenced by a failure of parallel orientation and a resultant abnormal migration in mice nullified for astrocyte-derived VEGF (Bozoyan et al, 2012). Our own study has shown that induced collapse of the RMS vascular network via conditional VEGF knock-down results in a complete failure of newborn neuronal precursors to out-migrate from the SVZ (Licht et al, 2010(Licht et al, , 2015.…”

Section: The Svz Vascular Nichementioning

confidence: 93%

The vascular niche in adult neurogenesis

Licht

2015

Mechanisms of Development

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Blood vessels (BVs) not only serve as conduits for oxygen and nutrients but may also fulfill perfusion-independent functions. A growing body of data suggests that blood vessels are an integral component of stem cell niches, including stem cell niches in the adult brain. This review summarizes in vivo studies supporting the contention that blood vessels may indeed control function of neuronal stem cells (NSCs) residing in the two major neurogenic niches of the adult brain, namely the sub-ventricular zone and the hippocampus. The review discusses different modes of BV-NSC communication and possible mechanisms by which BV may modulate NSC behavior and responses to external stimuli.

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Section: The Svz Vascular Nichementioning

confidence: 93%

The vascular niche in adult neurogenesis

Licht

2015

Mechanisms of Development

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“…VEGF-A is necessary for inducing proper vascular tube formation as well as for endothelial survival. At later stages, once vessels are maturing and stabilizing, they no longer depend on VEGF-A for their survival [28]. Interestingly, this maturation process is synchronized with the CNS vasculature's acquisition of BBB properties [28].…”

Section: Angiomodulin Antagonizes Vegf-a-induced Peripheral Vascular mentioning

confidence: 99%

“…At later stages, once vessels are maturing and stabilizing, they no longer depend on VEGF-A for their survival [28]. Interestingly, this maturation process is synchronized with the CNS vasculature's acquisition of BBB properties [28]. VEGF-A is also responsible for inducing vascular hyperpermeability.…”

Section: Angiomodulin Antagonizes Vegf-a-induced Peripheral Vascular mentioning

confidence: 99%

Angiomodulin (IGFBP7) is a cerebral specific angiocrine factor, but is probably not a blood–brain barrier inducer

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Atamny

et al. 2020

Fluids Barriers CNS

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Background: Several secreted factors have been identified as drivers of cerebral vasculature development and inducers of blood-brain barrier (BBB) differentiation. Vascular endothelial growth factor A (VEGF-A) is central for driving cerebral angiogenesis and Wnt family factors (Wnt7a, Wnt7b and norrin) are central for induction and maintenance of barrier properties. Expressed by developing neural tissue (neuron and glia progenitors), they influence the formation of central nervous system (CNS) vascular networks. Another type of factors are tissue-specific paracrine factors produced by endothelial cells (ECs), also known as 'angiocrine' factors, that provide instructive signals to regulate homeostatic and regenerative processes. Very little is known about CNS angiocrine factors and their role in BBB development. Angiomodulin (AGM) was reported to be expressed by developing vasculature and by pathological tumor vasculature. Here we investigated AGM in the developing CNS and its function as a potential BBB inducer. Methods:We analyzed microarray data to identify potential angiocrine factors specifically expressed at early stages of barrier formation. We then tested AGM expression with immunofluorescence and real-time PCR in various organs during development, post-natal and in adults. Permeability induction with recombinant proteins (Miles assay) was used to test potential interaction of AGM with VEGF-A. Results: Several angiocrine factors are differentially expressed by CNS ECs and AGM is a prominent CNS-specific angiocrine candidate. Contrary to previous reports, we found that AGM protein expression is specific to developing CNS endothelium and not to highly angiogenic developing vasculature in general. In skin vasculature we found that AGM antagonizes VEGF-A-induced vascular hyperpermeability. Finally, CNS AGM expression is not specific to BBB vasculature and AGM is highly expressed in non-BBB choroid-plexus vasculature. Conclusions:We propose AGM as a developmental CNS vascular-specific marker. AGM is not a pan-endothelial marker, nor a general marker for developing angiogenic vasculature. Thus, AGM induction in the developing CNS might be distinct from its induction in pathology. While AGM is able to antagonize VEGF-A-induced vascular hyperpermeability in the skin, its high expression levels in non-BBB CNS vasculature does not support its potential role as a BBB inducer. Further investigation including loss-of-function approaches might elucidate AGM function in the developing CNS.

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“…In this issue, Licht, Dor-Wollman, and colleagues report on their generation of a novel murine model that recapitulates specific temporal and regional phenotypes analogous to those of human PVL (13). Spe- Clinical vignette: An 8-year-old boy presents to the pediatric ICU after two days of cough with increasing secretions.…”

Section: Research Advancesmentioning

confidence: 99%

“…Based on these results, Licht, DorWollman, and colleagues conclude that VEGF blockade obliterates only those cortical vessels that remain in an immature, VEGF-dependent stage of development and propose that vascular maturation takes place in a sequential, wave-like fashion, with the periventricular vessels of the germinal matrix being the last to mature (13). Immaturity therefore renders vessels specifically susceptible to pathologic insult, which would explain why a restricted brain region is affected as well as the limited temcifically, the authors developed a bitransgenic mouse in which selective induction and deinduction of a secreted VEGF decoy receptor is accomplished by the presence or absence of tetracycline in the drinking water.…”

Section: Recommendationsmentioning

confidence: 99%