PDGF Receptor &amp;#946; Signaling in Pericytes Following Ischemic Brain Injury

Arimura, Koichi; Ago, Tetsuro; Kamouchi, Masahiro; Nakamura, Kuniyuki; Ishitsuka, Koji; Kuroda, Junya; Sugimori, Hiroshi; Ooboshi, Hiroaki; Sasaki, Tatsuya; Kitazono, Takanari

doi:10.2174/156720212799297100

Cited by 132 publications

(127 citation statements)

References 28 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: 59%

“…Immunohistochemistry and immunofluorescence were performed as described previously 26 and in Methods in the online-only Data Supplement. microtubule-associated protein 2 (MAP2), GFAP-, CD34-, platelet-derived growth factor receptor β (PDGFRβ)-, and F4/80-positive areas and infarct volumes were quantified using ImageJ software in a blinded manner as described in Methods in the online-only Data Supplement.…”

Section: Immunohistochemistry and Immunofluorescencementioning

confidence: 99%

“…Immunoblot analyses and quantitative polymerase chain reaction on brain tissues were performed as described previously 26 and in Methods in the online-only Data Supplement.…”

Section: Immunoblot Analysis and Quantitative Polymerase Chain Reactionmentioning

confidence: 99%

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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: 59%

Section: Immunohistochemistry and Immunofluorescencementioning

confidence: 99%

See 1 more Smart Citation

Early Reperfusion After Brain Ischemia Has Beneficial Effects Beyond Rescuing Neurons

Terabe

Ago

Wakisaka

et al. 2017

Stroke

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“…Fibrous tissues may prevent normal tissue recovery, particularly in the muscle where fibrosis has been shown to lead to progressive skeletal muscle injury, for example in Duchenne's muscular dystrophy (Acuna et al, 2014). Previous work has suggested that PDGFRβ+ pericytes contribute to scar formation (Arimura et al, 2012) and express fibroblast-associated markers (such as collagen IV, fibronectin and fibroblast surface proteins). Using a coll1a1 (collagen-1, α1) reporter mice to determine where scar-associated myofibroblasts generate extracellular matrix collagen type 1, Lin et al demonstrated that pericytes and perivascular muscle cells are a major source of myofibroblasts in a unilateral ureteral obstruction (UUO) kidney fibrosis model.…”

Section: Tissue Fibrosismentioning

confidence: 99%

Pericytes, mesenchymal stem cells and their contributions to tissue repair

Wong

Rowley

Redpath

et al. 2015

Pharmacology & Therapeutics

148

110

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Regenerative medicine using mesenchymal stem cells for the purposes of tissue repair has garnered considerable public attention due to the potential of returning tissues and organs to a normal, healthy state after injury or damage has occurred. To achieve this, progenitor cells such as pericytes and bone marrow-derived mesenchymal stem cells can be delivered exogenously, mobilised and recruited from within the body or transplanted in the form organs and tissues grown in the laboratory from stem cells. In this review, we summarise the recent evidence supporting the use of endogenously mobilised stem cell populations to enhance tissue repair along with the use of mesenchymal stem cells and pericytes in the development of engineered tissues. Finally, we conclude with an overview of currently available therapeutic options to manipulate endogenous stem cells to promote tissue repair.

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“…26 One microgram of total RNA was reverse-transcribed in a total volume of 20 mL, and 0.5 mL of the product was used as a template. The mRNA copy numbers were standardized using 18 s ribosomal RNA (18 s rRNA).…”

Section: Reverse Transcription-pcr and Real-time Pcrmentioning

confidence: 99%

Detrimental role of pericyte Nox4 in the acute phase of brain ischemia

Nishimura

Ago

Kuroda

et al. 2015

J Cereb Blood Flow Metab

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Pericytes are mural cells abundantly present in cerebral microvessels and play important roles, including the formation and maintenance of the blood-brain barrier. Nox4 is a major source of reactive oxygen species in cardiovascular cells and modulate cellular functions, particularly under pathological conditions. In the present study, we found that the expression of Nox4 was markedly induced in microvascular cells, including pericytes, in peri-infarct areas after middle cerebral artery occlusion stroke models in mice. The upregulation of Nox4 was greater in a permanent middle cerebral artery occlusion model compared with an ischemia/reperfusion transient middle cerebral artery occlusion model. We performed permanent middle cerebral artery occlusion on mice with Nox4 overexpression in pericytes (Tg-Nox4). Infarct volume was significantly greater with enhanced reactive oxygen species production and blood-brain barrier breakdown in peri-infarct areas in Tg-Nox4, compared with littermate controls. In cultured brain pericytes, Nox4 was significantly upregulated by hypoxia and was promptly downregulated by reoxygenation. Phosphorylation of NFkB and production of matrix metalloproteinase 9 were significantly increased in both cultured pericytes overexpressing Nox4 and in periinfarct areas in Tg-Nox4. Collectively, Nox4 is upregulated in pericytes in peri-infarct areas after acute brain ischemia and may enhance blood-brain barrier breakdown through activation of NFkB and matrix metalloproteinase 9, thereby causing enlargement of infarct volume.

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PDGF Receptor β Signaling in Pericytes Following Ischemic Brain Injury

Cited by 132 publications

References 28 publications

Early Reperfusion After Brain Ischemia Has Beneficial Effects Beyond Rescuing Neurons

Early Reperfusion After Brain Ischemia Has Beneficial Effects Beyond Rescuing Neurons

Pericytes, mesenchymal stem cells and their contributions to tissue repair

Detrimental role of pericyte Nox4 in the acute phase of brain ischemia

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