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Sökning: L773:0969 6970 > (2020-2023) > Vascular PDGFR-alph...

  • Nguyen, Quang Linh (författare)

Vascular PDGFR-alpha protects against BBB dysfunction after stroke in mice

  • Artikel/kapitelEngelska2021

Förlag, utgivningsår, omfång ...

  • 2020-09-12
  • Springer,2021
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:uu-450603
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-450603URI
  • https://doi.org/10.1007/s10456-020-09742-wDOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:144601472URI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • 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.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Okuno, NorikoUniv Toyama, Grad Sch Med & Pharmaceut Sci, Dept Pathol, Toyama 9300194, Japan. (författare)
  • Hamashima, TakeruUniv Toyama, Grad Sch Med & Pharmaceut Sci, Dept Pathol, Toyama 9300194, Japan. (författare)
  • Dang, Son TungUniv Toyama, Grad Sch Med & Pharmaceut Sci, Dept Pathol, Toyama 9300194, Japan. (författare)
  • Fujikawa, MiwaUniv Toyama, Grad Sch Med & Pharmaceut Sci, Dept Pathol, Toyama 9300194, Japan. (författare)
  • Ishii, YokoUniv Nagano, Fac Hlth & Human Dev, Dept Hlth Sci, Nagano, Japan. (författare)
  • Enomoto, AtsushiNagoya Univ, Dept Pathol, Grad Sch Med, Nagoya, Aichi, Japan. (författare)
  • Maki, TakakuniKyoto Univ, Grad Sch Med, Dept Neurol, Kyoto, Japan. (författare)
  • Nguyen, Hoang Ngoc108 Mil Cent Hosp, Stroke Ctr, Hanoi, Vietnam. (författare)
  • Nguyen, Van Tuyen (författare)
  • Fujimori, ToshihikoNatl Inst Basic Biol, Div Embryol, Okazaki, Aichi, Japan. (författare)
  • Mori, HisashiUniv Toyama, Grad Sch Med & Pharmaceut Sci, Dept Mol Neurosci, Toyama, Japan. (författare)
  • Andrae, JohannaUppsala universitet,Vaskulärbiologi(Swepub:uu)johaandr (författare)
  • Betsholtz, ChristerUppsala universitet,Vaskulärbiologi,Karolinska Inst, Integrated Cardio Metab Ctr, Huddinge, Sweden.(Swepub:uu)chbet517 (författare)
  • Takao, KeizoUniv Toyama, Life Sci Res Ctr, Div Anim Resources & Dev, Toyama, Japan. (författare)
  • Yamamoto, SeijiUniv Toyama, Grad Sch Med & Pharmaceut Sci, Dept Pathol, Toyama 9300194, Japan. (författare)
  • Sasahara, MasakiyoUniv Toyama, Grad Sch Med & Pharmaceut Sci, Dept Pathol, Toyama 9300194, Japan. (författare)
  • 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)

Sammanhörande titlar

  • Ingår i:Angiogenesis: Springer24, s. 35-460969-69701573-7209

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