The Neurovascular Link in Health and Disease: Molecular Mechanisms and Therapeutic Implications

Quaegebeur, Annelies; Lange, Christian; Carmeliet, Peter

doi:10.1016/j.neuron.2011.07.013

Cited by 228 publications

(276 citation statements)

References 149 publications

(172 reference statements)

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“…In fact, 17 unique collagen genes were down-regulated in the multi-miR-injected group PVN compared with controls. These findings may reflect deficits in cerebral circulation and/or blood-brain barrier permeability in the PVN, effects that would have significant impact on neuroendocrine function (36,37). Furthermore, the PVN is one of the most highly vascularized regions in the brain, suggesting that it may be particularly susceptible to developmental changes in circulation or permeability (38).…”

Section: Discussionmentioning

confidence: 99%

Transgenerational epigenetic programming via sperm microRNA recapitulates effects of paternal stress

Rodgers

Morgan

Leu

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

605

543

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Epigenetic signatures in germ cells, capable of both responding to the parental environment and shaping offspring neurodevelopment, are uniquely positioned to mediate transgenerational outcomes. However, molecular mechanisms by which these marks may communicate experience-dependent information across generations are currently unknown. In our model of chronic paternal stress, we previously identified nine microRNAs (miRs) that were increased in the sperm of stressed sires and associated with reduced hypothalamic-pituitaryadrenal (HPA) stress axis reactivity in offspring. In the current study, we rigorously examine the hypothesis that these sperm miRs function postfertilization to alter offspring stress responsivity and, using zygote microinjection of the nine specific miRs, demonstrated a remarkable recapitulation of the offspring stress dysregulation phenotype. Further, we associated long-term reprogramming of the hypothalamic transcriptome with HPA axis dysfunction, noting a marked decreased in the expression of extracellular matrix and collagen gene sets that may reflect an underlying change in blood-brain barrier permeability. We conclude by investigating the developmental impact of sperm miRs in early zygotes with single-cell amplification technology, identifying the targeted degradation of stored maternal mRNA transcripts including sirtuin 1 and ubiquitin protein ligase E3a, two genes with established function in chromatin remodeling, and this potent regulatory function of miRs postfertilization likely initiates a cascade of molecular events that eventually alters stress reactivity. Overall, these findings demonstrate a clear mechanistic role for sperm miRs in the transgenerational transmission of paternal lifetime experiences.transgenerational | epigenetic | stress | microRNA | paternal

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Section: Discussionmentioning

confidence: 99%

Transgenerational epigenetic programming via sperm microRNA recapitulates effects of paternal stress

Rodgers

Morgan

Leu

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

605

543

View full text Add to dashboard Cite

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“…In this study, we examined Nogo-B expression in vascular endothelial cells in HCC tissues from patients and investigated the role of endothelial Nogo-B in HCC growth. In addition, recent studies have provided evidence suggesting that neurovascular crosstalk was pretty important for certain neurological diseases [16,17]. Here, we also explored the role of endothelial Nogo-B in cancer progression.…”

Section: Introductionmentioning

confidence: 97%

WITHDRAWN: Endothelial Nogo-B suppresses cancer cell proliferation via a paracrine TGF-β/Smad signaling

Li¹,

Cheng²,

Huang³

et al. 2018

Oncotarget

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“…1 Vascular mural cells, including the very abundant capillary pericytes (PCs), are positioned at the interface between endothelial cells, neurons, and astrocytes. Experimental evidence supports a variety of functions of these cells: PCs influence the proliferation of endothelial cells during development and adult angiogenesis.…”

Section: Introductionmentioning

confidence: 99%

Early Loss of Pericytes and Perivascular Stromal Cell-Induced Scar Formation after Stroke

Fernández-Klett

Potas

Hilpert

et al. 2012

J Cereb Blood Flow Metab

197

249

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Despite its limited regenerative capacity, the central nervous system (CNS) shares more repair mechanisms with peripheral tissues than previously recognized. Scar formation is a ubiquitous healing mechanism aimed at patching tissue defects via the generation of fibrous extracellular matrix (ECM). This process, orchestrated by stromal cells, can unfavorably affect the capacity of tissues to restore function. Vascular mural cells have been found to contribute to scarring after spinal cord injury. In the case of stroke, little is known about the responses of pericytes (PCs) and stromal cells. Here, we show that capillary PCs are rapidly lost after cerebral ischemia in both experimental and human stroke. Coincident with this loss is a massive proliferation of resident platelet-derived growth factor receptor beta (PDGFRb) þ and CD105 þ stromal cells, which originate from the neurovascular unit and deposit ECM in the ischemic mouse brain. The presence of PDGFRb þ stromal cells demarcates a fibrotic, contracted, and macrophage-laden lesion core from the rim of hypertrophic astroglia in both experimental and human stroke. We suggest that a previously unrecognized population of CNS-resident stromal cells drives a dynamic process of scarring after cerebral ischemia, which appears distinct from the glial scar and represents a novel target for regenerative stroke therapies.

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The Neurovascular Link in Health and Disease: Molecular Mechanisms and Therapeutic Implications

Cited by 228 publications

References 149 publications

Transgenerational epigenetic programming via sperm microRNA recapitulates effects of paternal stress

Transgenerational epigenetic programming via sperm microRNA recapitulates effects of paternal stress

WITHDRAWN: Endothelial Nogo-B suppresses cancer cell proliferation via a paracrine TGF-β/Smad signaling

Early Loss of Pericytes and Perivascular Stromal Cell-Induced Scar Formation after Stroke

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