Angiogenesis of the blood‐brain barrier in vitro and the function of cerebral pericytes

Ramsauer, Markus; Krause, Dorothee; Dermietzel, Rolf

doi:10.1096/fj.01-0814fje

Cited by 157 publications

(92 citation statements)

References 60 publications

(53 reference statements)

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“…Neutralization of native VEGF decreases angiogenic activity, astrocyte proliferation, and results in large wound cavities in injured brain (Krum and Khaibullina, 2003). Astrocytes are potent regulators of brain capillary endothelial cell function and have a profound influence on the morphogenetic events underlying the organization of the vessel wall (Ramsauer et al, 2002). The astrocyte network strongly affects vascular patterning (Fruttiger et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Angiopoietin1/TIE2 and VEGF/FLK1 Induced by MSC Treatment Amplifies Angiogenesis and Vascular Stabilization after Stroke

Zacharek¹,

Chen²,

Cui³

et al. 2007

J Cereb Blood Flow Metab

252

201

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Bone marrow stromal cells (MSCs) increase vascular endothelial growth factor (VEGF) expression and promote angiogenesis after stroke. Angiopoietin-1 (Ang1) and its receptor Tie2 mediate vascular integrity and angiogenesis as does VEGF and its receptors. In this study, we tested whether MSC treatment of stroke increases Ang1/Tie2 expression, and whether Ang1/Tie2 with VEGF/ vascular endothelial growth factor receptor 2 (VEGFR2) (Flk1), in combination, induced by MSCs enhances angiogenesis and vascular integrity. Male Wistar rats were subjected to middle cerebral artery occlusion (MCAo) and treated with or without MSCs. Marrow stromal cell treatment significantly decreased blood-brain barrier (BBB) leakage and increased Ang1,

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Section: Discussionmentioning

confidence: 99%

Angiopoietin1/TIE2 and VEGF/FLK1 Induced by MSC Treatment Amplifies Angiogenesis and Vascular Stabilization after Stroke

Zacharek¹,

Chen²,

Cui³

et al. 2007

J Cereb Blood Flow Metab

252

201

View full text Add to dashboard Cite

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“…4 In vitro experiments show that pericytes stabilize capillary-like structures. 5 A recent study has also suggested that pericyte constriction may be the cause of the long-lasting decrease of cerebral blood flow, thus damaging the BBB. 6 Pericytes have also been shown to be involved in angiogenesis and EC TJ formation, which is another important constituent of the BBB.…”

Section: See Cover Imagementioning

confidence: 99%

EphrinB2 Activation Enhances Vascular Repair Mechanisms and Reduces Brain Swelling After Mild Cerebral Ischemia

Ghori

Freimann

Nieminen-Kelhä

et al. 2017

ATVB

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Objective— Cerebral edema caused by the disruption of the blood–brain barrier is a major complication after stroke. Therefore, strategies to accelerate and enhance neurovascular recovery after stroke are of prime interest. Our main aim was to study the role of ephrinB2/EphB4 signaling in mediating the vascular repair and in blood–brain barrier restoration after mild cerebral ischemia occlusion/reperfusion. Approach and Results— Here, we show that the guidance molecule ephrinB2 plays a key role in neurovascular protection and blood–brain barrier restoration after stroke. In a focal stroke model, we characterize the stroke-induced damage to cerebral blood vessels and their subsequent endogenous repair on a cellular, molecular, and functional level. EphrinB2 and its tyrosine kinase receptor EphB4 are upregulated early after stroke by endothelial cells and perivascular support cells, in parallel to their reassembly during neurovascular recovery. Using both retroviral and pharmacological approaches, we show that the inhibition of ephrinB2/EphB4 signaling suppresses post-middle cerebral artery occlusion neurovascular repair mechanisms resulting in an aggravation of brain swelling. In contrast, the activation of ephrinB2 after brain ischemia leads to an increased pericyte recruitment and increased endothelial–pericyte interaction, resulting in an accelerated neurovascular repair after ischemia. Conclusions— We show that reducing swelling could result in improved outcome because of reduction in damaged brain tissue. We also identify a novel role for ephrinB2/EphB4 signaling in the maintenance of the neurovascular homeostasis and provide a novel therapeutic approach in reducing brain swelling after stroke.

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“…All cultures were prepared from newborn or perinatal rats as described previously (51). They were 70 -80% pure.…”

Section: Construction Of Eukaryotic Expression and Transient Transfecmentioning

confidence: 99%

Identification and Characterization of ZFP-57, a Novel Zinc Finger Transcription Factor in the Mammalian Peripheral Nervous System

Alonso

Zoidl

Taveggia

et al. 2004

Journal of Biological Chemistry

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To isolate new zinc finger genes expressed at early stages of peripheral nerve development, we have used PCR to amplify conserved zinc finger sequences. RNA from rat embryonic day 12 and 13 sciatic nerves, a stage when nerves contain Schwann cell precursors, was used to identify several genes not previously described in Schwann cells. One of them, zinc finger protein (ZFP)-57, proved to be the homologue of a mouse gene found in F9 teratocarcinoma cells. Its mRNA expression profile within embryonic and adult normal and transected peripheral nerves, and its distribution in the rest of the nervous system is described. High levels of expression are seen in embryonic nerves and spinal cord. These drop rapidly during the first few weeks after birth, a pattern mirrored in other parts of the nervous system. ZFP-57 localizes to the nucleus of Schwann and other cells. The sequence contains an N-terminal Krü ppel-associated box (KRAB) domain and ZFP-57 constructs containing green fluorescent protein reveal that the protein colocalizes with heterochromatin protein 1␣ to centromeric heterochromatin in a characteristic speckled pattern in NIH3T3 cells. The KRAB domain is required for this localization, because constructs lacking it target the protein to the nucleus but not to the centromeric heterochromatin. When fused to a heterologous DNA binding domain, the KRAB domain of ZFP-57 represses transcription, and fulllength ZFP-57 represses Schwann cell transcription from myelin basic protein and P 0 promoters in co-transfection assays. Zfp-57 mRNA is up-regulated in Schwann cells in response to leukemia inhibitory factor and fibroblast growth factor 2.The major stages in the embryonic development of Schwann cells in rodent peripheral nerves have been defined at the cellular level. Nearly all cells isolated from nerves of embryo day (E) 1 14/E15 rats or E12/E13 mice are Schwann cell precursors (1-4). They are derived from the neural crest and give rise to the immature Schwann cells of late embryonic and early postnatal nerves. These cells are the source of the myelinating or non-myelinating cells of adult nerves. Schwann cell precursors can be distinguished from immature Schwann cells on the one hand and from neural crest cells on the other by a number of criteria, including differences in the regulation of survival and DNA synthesis and antigenic phenotype (5-8).A number of transcription factors are involved in the cellular transitions that take place in embryonic nerves and early postnatal nerves (9, 10). The HMG domain factor Sox-10 is expressed in most or all neural crest cells and is required for the formation of the glial lineage (11,12). It is also likely to be important in later stages of development, because it has the capacity to synergize with Krox-20 (Egr-2) (see below) to activate the connexin 32 promoter (13-15). Two transcription factors, the POU domain proteins Oct-6 (SCIP, Tst-1, Pou3f1) and Brn-2 are involved in the timing of myelination (16 -18), whereas Schwann cells in nerves of mice that are null for the zi...

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Angiogenesis of the blood‐brain barrier in vitro and the function of cerebral pericytes

Cited by 157 publications

References 60 publications

Angiopoietin1/TIE2 and VEGF/FLK1 Induced by MSC Treatment Amplifies Angiogenesis and Vascular Stabilization after Stroke

Angiopoietin1/TIE2 and VEGF/FLK1 Induced by MSC Treatment Amplifies Angiogenesis and Vascular Stabilization after Stroke

EphrinB2 Activation Enhances Vascular Repair Mechanisms and Reduces Brain Swelling After Mild Cerebral Ischemia

Identification and Characterization of ZFP-57, a Novel Zinc Finger Transcription Factor in the Mammalian Peripheral Nervous System

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