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Vascular PDGFR-alph...
Vascular PDGFR-alpha protects against BBB dysfunction after stroke in mice
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Nguyen, Quang Linh (author)
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- Okuno, Noriko (author)
- Univ Toyama, Grad Sch Med & Pharmaceut Sci, Dept Pathol, Toyama 9300194, Japan.
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- Hamashima, Takeru (author)
- Univ Toyama, Grad Sch Med & Pharmaceut Sci, Dept Pathol, Toyama 9300194, Japan.
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- Dang, Son Tung (author)
- Univ Toyama, Grad Sch Med & Pharmaceut Sci, Dept Pathol, Toyama 9300194, Japan.
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- Fujikawa, Miwa (author)
- Univ Toyama, Grad Sch Med & Pharmaceut Sci, Dept Pathol, Toyama 9300194, Japan.
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- Ishii, Yoko (author)
- Univ Nagano, Fac Hlth & Human Dev, Dept Hlth Sci, Nagano, Japan.
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- Enomoto, Atsushi (author)
- Nagoya Univ, Dept Pathol, Grad Sch Med, Nagoya, Aichi, Japan.
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- Maki, Takakuni (author)
- Kyoto Univ, Grad Sch Med, Dept Neurol, Kyoto, Japan.
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- Nguyen, Hoang Ngoc (author)
- 108 Mil Cent Hosp, Stroke Ctr, Hanoi, Vietnam.
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Nguyen, Van Tuyen (author)
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- Fujimori, Toshihiko (author)
- Natl Inst Basic Biol, Div Embryol, Okazaki, Aichi, Japan.
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- Mori, Hisashi (author)
- Univ Toyama, Grad Sch Med & Pharmaceut Sci, Dept Mol Neurosci, Toyama, Japan.
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- Andrae, Johanna (author)
- Uppsala universitet,Vaskulärbiologi
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- Betsholtz, Christer (author)
- Uppsala universitet,Vaskulärbiologi,Karolinska Inst, Integrated Cardio Metab Ctr, Huddinge, Sweden.
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- Takao, Keizo (author)
- Univ Toyama, Life Sci Res Ctr, Div Anim Resources & Dev, Toyama, Japan.
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- Yamamoto, Seiji (author)
- Univ Toyama, Grad Sch Med & Pharmaceut Sci, Dept Pathol, Toyama 9300194, Japan.
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- Sasahara, Masakiyo (author)
- Univ Toyama, Grad Sch Med & Pharmaceut Sci, Dept Pathol, Toyama 9300194, Japan.
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Univ Toyama, Grad Sch Med & Pharmaceut Sci, Dept Pathol, Toyama 9300194, Japan Univ Nagano, Fac Hlth & Human Dev, Dept Hlth Sci, Nagano, Japan. (creator_code:org_t)
- 2020-09-12
- 2021
- English.
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In: Angiogenesis. - : Springer. - 0969-6970 .- 1573-7209. ; 24, s. 35-46
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Blood-brain barrier (BBB) dysfunction underlies the pathogenesis of many neurological diseases. Platelet-derived growth factor receptor-alpha (PDGFR alpha) induces hemorrhagic transformation (HT) downstream of tissue plasminogen activator in thrombolytic therapy of acute stroke. Thus, PDGFs are attractive therapeutic targets for BBB dysfunction. In the present study, we examined the role of PDGF signaling in the process of tissue remodeling after middle cerebral arterial occlusion (MCAO) in mice. Firstly, we found that imatinib increased lesion size after permanent MCAO in wild-type mice. Moreover, imatinib-induced HT only when administrated in the subacute phase of MCAO, but not in the acute phase. Secondly, we generated genetically mutated mice (C-KO mice) that showed decreased expression of perivascular PDGFR alpha. Additionally, transient MCAO experiments were performed in these mice. We found that the ischemic lesion size was not affected; however, the recruitment of PDGFR alpha/type I collagen-expressing perivascular cells was significantly downregulated, and HT and IgG leakage was augmented only in the subacute phase of stroke in C-KO mice. In both experiments, we found that the expression of tight junction proteins and PDGFR beta-expressing pericyte coverage was not significantly affected in imatinib-treated mice and in C-KO mice. The specific implication of PDGFR alpha signaling was suggestive of protective effects against BBB dysfunction during the subacute phase of stroke. Vascular TGF-beta 1 expression was downregulated in both imatinib-treated and C-KO mice, along with sustained levels of MMP9. Therefore, PDGFR alpha effects may be mediated by TGF-beta 1 which exerts potent protective effects in the BBB.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- Ischemic stroke
- Hemorrhagic transformation
- Perivascular fibroblast-like cells
- PDGF receptor-alpha
- Imatinib
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Nguyen, Quang Li ...
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Okuno, Noriko
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Hamashima, Taker ...
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Dang, Son Tung
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Fujikawa, Miwa
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Ishii, Yoko
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show more...
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Enomoto, Atsushi
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Maki, Takakuni
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Nguyen, Hoang Ng ...
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Nguyen, Van Tuye ...
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Fujimori, Toshih ...
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Mori, Hisashi
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Andrae, Johanna
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Betsholtz, Chris ...
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Takao, Keizo
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Yamamoto, Seiji
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Sasahara, Masaki ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
- Articles in the publication
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Angiogenesis
- By the university
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Uppsala University
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Karolinska Institutet