Brain homeostasis: VEGF receptor 1 and 2—two unequal brothers in mind

Wittko-Schneider, Ina M.; Schneider, Fabian T.; Plate, Karl H.

doi:10.1007/s00018-013-1279-3

Cited by 51 publications

(42 citation statements)

References 188 publications

(288 reference statements)

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“…Within adult CNS tissues the receptor VEGFR2 is seen in neurones of human, rat and primate brain [4,24,27,39,41], in oligodendroglial progenitors [19], in human microglia [12] and in human spinal neurones [6]. VEGFR2 has also been observed within VSMC, in small arteries of human spinal cord [6] and in blood vessels of peripheral tissues [8,36,37].…”

Section: Discussionmentioning

confidence: 99%

“…This is supported by our finding that endothelial VEGFR2 was not widespread. Physiological effects of VEGFR2 in adult brain include migration of neuronal progenitor and oligodendrocyte progenitor cells [19,41].…”

Section: Discussionmentioning

confidence: 99%

“…Within multiple sclerosis lesions, endothelial VEGFR2 is induced by the inflammatory cytokine IL-1β, and drives local blood-brain barrier permeability (due to endothelial claudin-5 breakdown) [1,2]. VEGFR2 expression is strongly induced in VSMC following IL-6 exposure [43], further supporting a role for VEGFR2 in the response to neuroinflammatory stimuli [30,41]. VEGFR2 is also upregulated following acute ischemic challenge [15,33,39].…”

Section: Discussionmentioning

confidence: 99%

“…The trans-membrane tyrosine kinase-linked receptor VEGFR2 (also known as KDR or Flk-1) is a potent determinant of cell fate [30,41]. Activation of VEGFR2 in endothelial cells by the canonical ligand VEGF is associated with angiogenesis and increased vascular permeability.…”

Section: Introductionmentioning

confidence: 99%

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Age-dependent expression of VEGFR2 in deep brain arteries in small vessel disease, CADASIL, and healthy brains

Ahmed-Jushuf

Jiwa

Arwani

et al. 2016

Neurobiology of Aging

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Vascular myocytes are central to brain aging. Small vessel disease (SVD; arteriolosclerosis) is a widespread cause of lacunar stroke and vascular dementia, and is characterised by fibrosis and depletion of vascular myocytes in small penetrating arteries. Vascular endothelial growth factor (VEGF) is associated with brain aging, and VEGFR2 is a potent determinant of cell fate. Here, we tested whether VEGFR2 in vascular myocytes is associated with older age and SVD in human brain.VEGFR2 immunolabelling in deep grey matter was assessed in older people with or without moderate-severe SVD, or in younger people without brain pathology or with a monogenic form of SVD (CADASIL). All cases were without Alzheimer's disease pathology. Myocyte VEGFR2 was associated with increasing age (p=0.0026) but not with SVD pathology or with sclerotic index or blood vessel density. We conclude that VEGFR2 is consistently expressed in small artery myocytes of older people, and may mediate effects of VEGF on brain vascular aging.[word count: 156; <170]

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Age-dependent expression of VEGFR2 in deep brain arteries in small vessel disease, CADASIL, and healthy brains

Ahmed-Jushuf

Jiwa

Arwani

et al. 2016

Neurobiology of Aging

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“…16 In the central nervous system, VEGF not only exerts its effect on the vascular system, but also helps to maintain the neural homeostasis and neural development. 17 VEGF is upregulated during various pathological events in the central nervous system, including ischemia, 18 cold lesions, spinal cord injuries, brain contusion and direct wounding. 19 It has also been reported that VEGF had a neuroprotective role in spinal cord injury.…”

Section: Discussionmentioning

confidence: 99%

Bosentan protects the spinal cord from ischemia reperfusion injury in rats through vascular endothelial growth factor receptors

et al. 2014

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Study design: Experimental study. Objectives: To investigate whether Bosentan, an endothelin-A/-B dual receptor antagonist, could protect neurons after spinal cord ischemia reperfusion (SCIR) injury in rats and its underlying signaling pathway. Setting: Department of Neurosurgery, the Second Affiliated Hospital, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi Province, China. Methods: Sprague-Dawley rats were randomly divided into two groups, saline group (IRS, n ¼ 48) and Bosentan group (IRB, 5 mg kg À1 , n ¼ 48). After ischemia for 1 h with occlusion of the infrarenal aorta, spinal cord were reperfused for 6h, 12h, 24h, 3d, 5d, and 7d separately. Enzyme-linked immunosorbent assay was used to detect vascular endothelial growth factor (VEGF) in serum. Immunohistochemistry was performed to detect protein expression of VEGF, VEGF receptor 1 (FLT-1) and VEGF receptor 2 (FLK-1). Gene expressions of VEGF and its receptors were evaluated using the quantitative reverse transcription polymerase chain reaction. Results: Compared with the IRS group, gene and protein expressions of VEGF, FLT-1 and FLK-1 were significantly increased (Po0.05), so was the concentration of VEGF in plasma (Po0.05). FLK-1 was expressed on spinal cord neurons.

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Stoichiometric Post‐Modification of Hydrogel Microparticles Dictates Neural Stem Cell Fate in Microporous Annealed Particle Scaffolds

et al. 2022

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into the cell types of the central nervous system, [2] they are an ideal target for brain repair after injury. [3] Post-injury, such as traumatic brain injury or stroke, NPCs travel toward the damaged site, however, they mainly remain in the surrounding region only. [4] We have previously shown that injecting MAP scaffolds in the stroke cavity increased the recruitment of NPCs toward the stroke site and resulted in NPC infiltration into the stroke core. [5,6] This provides an opportunity to modulate NPC fate and lead to improved endogenous regeneration by tailoring the microgels in our MAP scaffold.Hydrogels have historically been used to culture [7] and/or transplant [8] cells in vitro and in vivo, respectively. Their use as extracellular matrix mimics allows for studying various chemical and physical properties that are necessary to derive desired cellular interactions and phenotypes. [7] The most utilized hydrogel systems for NPC renewal or differentiation are nonporous hydrogels formed through crosslinking biocompatible polymers decorated with laminin-derived peptides. [9] These hydrogels can easily be produced with tailored properties, for example varying degrees of degradability and stiffnesses, and NPCs can be seeded inside or on top of the gels. However, conflicting results arise when investigating NPC seeding within or on top of hydrogel Microporous annealed particle (MAP) scaffolds are generated from assembled hydrogel microparticles (microgels). It has been previously demonstrated that MAP scaffold are porous, biocompatible, and recruit neural progenitor cells (NPCs) to the stroke cavity after injection into the stroke core. Here, the goal is to study NPC fate inside MAP scaffolds in vitro. To create plain microgels that can later be converted to contain different types of bioactivities, the inverse electron-demand Diels-Alder reaction between tetrazine and norbornene is utilized, which allows the post-modification of plain microgels stoichiometrically. As a result of adhesive peptide attachment, NPC spreading leads to contractile force generation which can be recorded by tracking microgel displacement. Alternatively, non-adhesive peptide integration results in neurosphere formation that grows within the void space of MAP scaffolds. Although the formed neurospheres do not impose a contractile force on the scaffolds, they are seen to continuously transverse the scaffolds. It is concluded that MAP scaffolds can be engineered to either promote neurogenesis or enhance stemness depending on the chosen post-modifications of the microgels, which can be key in modulating their phenotypes in various applications in vivo.

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Brain homeostasis: VEGF receptor 1 and 2—two unequal brothers in mind

Cited by 51 publications

References 188 publications

Age-dependent expression of VEGFR2 in deep brain arteries in small vessel disease, CADASIL, and healthy brains

Age-dependent expression of VEGFR2 in deep brain arteries in small vessel disease, CADASIL, and healthy brains

Bosentan protects the spinal cord from ischemia reperfusion injury in rats through vascular endothelial growth factor receptors

Stoichiometric Post‐Modification of Hydrogel Microparticles Dictates Neural Stem Cell Fate in Microporous Annealed Particle Scaffolds

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