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- Dang, Thanh Chung, et al.
(author)
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Powerful Homeostatic Control of Oligodendroglial Lineage by PDGFR alpha in Adult Brain
- 2019
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In: Cell Reports. - : CELL PRESS. - 2211-1247. ; 27:4, s. 1073-1089
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Journal article (peer-reviewed)abstract
- Oligodendrocyte progenitor cells (OPCs) are widely distributed cells of ramified morphology in adult brain that express PDGFR alpha and NG2. They retain mitotic activities in adulthood and contribute to oligodendrogenesis and myelin turnover; however, the regulatory mechanisms of their cell dynamics in adult brain largely remain unknown. Here, we found that global Pdgfra inactivation in adult mice rapidly led to elimination of OPCs due to synchronous maturation toward oligodendrocytes. Surprisingly, OPC densities were robustly reconstituted by the active expansion of Nestin(+) immature cells activated in meninges and brain parenchyma, as well as a few OPCs that escaped from Pdgfra inactivation. The multipotent immature cells were induced in the meninges of Pdgfra-inactivated mice, but not of control mice. Our findings revealed powerful homeostatic control of adult OPCs, engaging dual cellular sources of adult OPC formation. These properties of the adult oligodendrocyte lineage and the alternative OPC source may be exploited in regenerative medicine.
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2. |
- Nguyen, Quang Linh, et al.
(author)
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Vascular PDGFR-alpha protects against BBB dysfunction after stroke in mice
- 2021
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In: Angiogenesis. - : Springer. - 0969-6970 .- 1573-7209. ; 24, s. 35-46
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Journal article (peer-reviewed)abstract
- 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.
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3. |
- Quang-Thuy, Ha, et al.
(author)
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A Bisimulation-based Method of Concept Learning for Knowledge Bases in Description Logics
- 2012
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In: SoICT 2012 - 3rd International Symposium on Information and Communication Technology. - New York, New York, USA : ACM Press. ; , s. 241-249
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Conference paper (peer-reviewed)abstract
- We develop the first bisimulation-based method of concept learning, called BBCL, for knowledge bases in description logics (DLs). Our method is formulated for a large class of useful DLs, with well-known DLs like ALC, SHIQ, SHOIQ, SROIQ. As bisimulation is the notion for characterizing indis-cernibility of objects in DLs, our method is natural and very promising.
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