Possible involvement of basic FGF in the upregulation of PDGFRβ in pericytes after ischemic stroke

Nakamura, Kuniyuki; Arimura, Koichi; Nishimura, Ataru; Terabe, Masaki; Yoshikawa, Yoji; Makihara, Noriko; Wakisaka, Yoshinobu; Kuroda, Junya; Kamouchi, Masahiro; Ooboshi, Hiroaki; Kitazono, Takanari; Ago, Tetsuro

doi:10.1016/j.brainres.2015.11.003

Cited by 62 publications

(50 citation statements)

References 33 publications

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“…We and others have reported that PDGFRβ-positive pericytes produce various trophic factors, such as bFGF (basic fibroblast growth factor), NGF (nerve growth factor), BDNF (brain-derived neurotrophic factor), and NT-3 (neurotrophin-3), that are involved in astrocyte survival and activation. 14,26,37 The experiments using PDGFRβ +/-mice support the concept that intrainfarct fibrosis may enhance peri-infarct astrogliosis ( Figure 5). …”

Section: Roles Of Cd34-positive Endothelial Cells and Pdgfrβ-positivesupporting

confidence: 57%

Early Reperfusion After Brain Ischemia Has Beneficial Effects Beyond Rescuing Neurons

Terabe

Ago

Wakisaka

et al. 2017

Stroke

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Background and Purpose-Recent studies show that successful endovascular thrombectomy 6 to 12 hours after stroke onset enhances functional outcomes 3 months later. In this study, we investigated the effects of reperfusion after ischemia on repair processes in the ischemic areas, as well as on functional recovery, using mouse stroke models. Methods-We examined time-dependent histological changes and functional recovery after transient middle cerebral artery occlusion of different durations, including permanent middle cerebral artery occlusion, using the CB-17 (CB-17/lcr-+/+Jcl) mouse strain, which has poor pial collateral blood flow. Results-Large microtubule-associated protein 2-negative areas of neuronal death were produced in mice subjected to ≥60 minutes of ischemia followed by reperfusion on day 1, while restricted microtubule-associated protein 2-negative regions were observed in mice subjected to a 45-minute period of ischemia. A substantial reduction in microtubule-associated protein 2-negative areas was observed on day 7 in mice given early reperfusion and was associated with better functional recovery. Klüver-Barrera staining demonstrated that white matter injury on day 1 was significantly lesser in mice with reperfusion. Immunohistochemistry and electron microscopy revealed that a greater number of endothelial cells were present in the infarct areas in mice with earlier reperfusion and were associated with a more rapid recruitment of plateletderived growth factor receptor β-positive pericytes and subsequent intrainfarct fibrosis. Early reperfusion also resulted in a greater accumulation of glial fibrillary acidic protein-positive astrocytes in peri-infarct areas. Peri-infarct astrogliosis was attenuated in platelet-derived growth factor receptor β heterozygous knockout mice. Conclusions-Early reperfusion after ischemia enhances the survival of endothelial cells and pericytes within ischemic areas even after the infarct is established, resulting in efficient intrainfarct fibrosis and peri-infarct astrogliosis. These effects might be associated with efficient peri-infarct reorganization and functional recovery. in peri-infarct areas in experimental researches, although this remains controversial. 21,22 Furthermore, it is experimentally suggested that efficient fibrotic formation within areas of infarct may promote peri-infarct astrogliosis. 23 Thus, if these repair processes are associated with functional recovery, apparent infarct volumes at early phases may not be suitable for predicting functional outcome.To date, few papers have focused on the effects of reperfusion on poststroke repair processes in both animals and human. In the present study, we hypothesized that early reperfusion might elicit efficient tissue repair, such as intrainfarct fibrosis and peri-infarct astrogliosis, and lead to functional recovery even if it does not prevent neuronal death within the ischemic areas. To examine the precise effects of ischemia-reperfusion in the MCA, we performed tMCAO of various durations, as well as perm...

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Section: Roles Of Cd34-positive Endothelial Cells and Pdgfrβ-positivesupporting

confidence: 57%

Early Reperfusion After Brain Ischemia Has Beneficial Effects Beyond Rescuing Neurons

Terabe

Ago

Wakisaka

et al. 2017

Stroke

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“…Here, we employed a rabbit model receiving media‐adventitia lentiviral injection to investigate the therapeutic potential of FGF‐2 + PDGF‐BB for increasing plaque neovessel maturity. FGF‐2 and PDGF‐BB synergistic effects have been investigated in cancers and some ischaemic diseases; however, the results were controversial . In rat and rabbit ischaemic hindlimb models, FGF‐2 and PDGF‐BB synergistically induced stable and relatively mature neovessels, but overexpression of FGF‐2 and PDGF‐BB in murine fibrosarcomas led to formation of high‐density primitive vascular plexuses that were poorly coated with pericytes and vascular SMCs .…”

Section: Discussionmentioning

confidence: 99%

Fibroblast growth factor‐2/platelet‐derived growth factor enhances atherosclerotic plaque stability

Yang

Liu

Song

et al. 2019

J Cellular Molecular Medi

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Increased immature neovessels contribute to plaque growth and instability. Here, we investigated a method to establish functional and stable neovessel networks to increase plaque stability. Rabbits underwent aortic balloon injury and were divided into six groups: sham, vector and lentiviral transfection with vascular endothelial growth factor‐A (VEGF)‐A, fibroblast growth factor (FGF)‐2, platelet‐derived growth factor (PDGF)‐BB and FGF‐2 + PDGF‐BB. Lentivirus was percutaneously injected into the media‐adventitia of the abdominal aorta by intravascular ultrasound guidance, and plaque‐rupture rate, plaque‐vulnerability index and plaque neovessel density at the injection site were evaluated. Confocal microscopy, Prussian Blue assay, Evans Blue, immunofluorescence and transmission electron microscopy were used to assess neovessel function and pericyte coverage. To evaluate the effect of FGF‐2/PDGF‐BB on pericyte migration, we used the mesenchymal progenitor cell line 10T1/2 as an in vitro model. VEGF‐A‐ and FGF‐2‐overexpression increased the number of immature neovessels, which caused intraplaque haemorrhage and inflammatory cell infiltration, eventually resulting in the plaque vulnerability; however, FGF‐2/PDGF‐BB induced mature and functional neovessels, through increased neovessel pericyte coverage. Additionally, in vitro analysis of 10T1/2 cells revealed that FGF‐2/PDGF‐BB induced epsin‐2 expression and enhanced the VEGF receptor‐2 degradation, which negatively regulated pericyte function consistent with the in vivo data. These results showed that the combination of FGF‐2 and PDGF‐BB promoted the function and maturation of plaque neovessels, thereby representing a novel potential treatment strategy for vulnerable plaques.

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“…Authors suggest that bFGF may activate pericytes functions via the interaction with platelet‐derived growth factor beta polypeptide‐receptor beta (PDGF‐BB) through the upregulation of PDGFR‐ β in CNS pericytes, which might contribute to neuroprotective and angiogenic actions (Nakamura et al . ). On the other hand, other authors observed that pericytes release the soluble form of PDGFR‐ β after brain microvascular damage in patients with dementia and Alzheimer Disease (AD; Sagare et al .…”

Section: Brain Mscs and Pericytesmentioning

confidence: 97%

“…; Nakamura et al . ). Moreover, MSCs/pericytes grafted into malignant brain tumors, associate closely and integrate to tumor vessels (Bexell et al .…”

Section: Pathological Implications Of Pericytesmentioning

confidence: 97%

“…A recent study demonstrated that bFGF (FGF2) upregulates the expression of PDGFR-b in cultured central nervous system (CNS) pericytes in response to acidification in vitro and in peri-infarct areas after ischemic stroke in vivo. Authors suggest that bFGF may activate pericytes functions via the interaction with platelet-derived growth factor beta polypeptide-receptor beta (PDGF-BB) through the upregulation of PDGFR-b in CNS pericytes, which might contribute to neuroprotective and angiogenic actions (Nakamura et al 2016). On the other hand, other authors observed that pericytes release the soluble form of PDGFR-b after brain microvascular damage in patients with dementia and Alzheimer Disease (AD; Sagare et al 2015).…”

Section: Brain Mscs and Pericytesmentioning

confidence: 99%

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Brain mesenchymal stem cells: physiology and pathological implications

Pombero

García-López²

2016

Dev Growth Differ

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Mesenchymal stem cells (MSCs) are defined as progenitor cells that give rise to a number of unique, differentiated mesenchymal cell types. This concept has progressively evolved towards an all-encompassing concept including multipotent perivascular cells of almost any tissue. In central nervous system, pericytes are involved in blood-brain barrier, and angiogenesis and vascular tone regulation. They form the neurovascular unit (NVU) together with endothelial cells, astrocytes and neurons. This functional structure provides an optimal microenvironment for neural proliferation in the adult brain. Neurovascular niche include both diffusible signals and direct contact with endothelial and pericytes, which are a source of diffusible neurotrophic signals that affect neural precursors. Therefore, MSCs/pericyte properties such as differentiation capability, as well as immunoregulatory and paracrine effects make them a potential resource in regenerative medicine.

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Possible involvement of basic FGF in the upregulation of PDGFRβ in pericytes after ischemic stroke

Cited by 62 publications

References 33 publications

Early Reperfusion After Brain Ischemia Has Beneficial Effects Beyond Rescuing Neurons

Early Reperfusion After Brain Ischemia Has Beneficial Effects Beyond Rescuing Neurons

Fibroblast growth factor‐2/platelet‐derived growth factor enhances atherosclerotic plaque stability

Brain mesenchymal stem cells: physiology and pathological implications

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