Differential regulation of angiogenesis in the developing mouse brain in response to exogenous activation of the hypoxia-inducible transcription factor system.
Brain Res
; 1688: 91-102, 2018 06 01.
Article
em En
| MEDLINE
| ID: mdl-29548688
Angiogenesis due to hypoxic-ischemic (HI) injury represents a crucial compensatory mechanism of the developing brain that is mainly regulated by hypoxia-inducible transcription factors (HIF). Pharmacological stimulation of HIF is suggested as a neuroprotective option, however, studies of its effects on vascular development are limited. We analyzed the influence of the prolyl-4-hydroxylase inhibitor (PHI), FG-4497, and erythropoietin (rhEPO) on post-hypoxic angiogenesis (angiogenic growth factors, vessel structures) in the developing mouse brain (P7) assessed after a regeneration period of 72â¯h. Exposure to systemic hypoxia (8% O2, 6â¯h) was followed by treatment (i.p.) with rhEPO (2500/5000â¯IU/kg) at 0, 24 and 48â¯h or FG-4497 (60/100â¯mg/kg) compared to controls. In response to FG-4497 treatment cortical and hippocampal vessel area and branching were significantly increased compared to controls. This was associated with elevated ANGPT-2 as well as decreased ANGPT-1 and TIE-2 mRNA levels. In response to rhEPO, mildly increased angiogenesis was associated with elevated ANGPT-2 but also TIE-2 mRNA levels in comparison to controls. In conclusion, present data demonstrate a differential regulation of the angiopoietin/TIE-2 system in response to PHI and rhEPO in the post-hypoxic developing brain pointing to potential functional consequences for vascular regeneration and vessel development.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Regeneração
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Encéfalo
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Hipóxia-Isquemia Encefálica
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Fator 1 Induzível por Hipóxia
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Neovascularização Patológica
Limite:
Animals
Idioma:
En
Revista:
Brain Res
Ano de publicação:
2018
Tipo de documento:
Article