Differential regulation of angiogenesis in the developing mouse brain in response to exogenous activation of the hypoxia-inducible transcription factor system
| Autor: | Andreas Feigenspan, Gudrun Boie, Regina Trollmann, M Richter, Susan Jung, Theresa Mühlberger, Florian Brackmann |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Angiogenesis Apoptosis Hippocampal formation Neuroprotection Angiopoietin-2 Angiopoietin 03 medical and health sciences 0302 clinical medicine Internal medicine Angiopoietin-1 medicine Animals Regeneration Erythropoietin Molecular Biology Transcription factor Neovascularization Pathologic business.industry General Neuroscience Brain Prolyl-Hydroxylase Inhibitors Differential regulation Hypoxia (medical) Isoquinolines Receptor TIE-2 Mice Inbred C57BL 030104 developmental biology Endocrinology Hypoxia-Ischemia Brain Hypoxia-Inducible Factor 1 Neurology (clinical) medicine.symptom business 030217 neurology & neurosurgery Signal Transduction Developmental Biology medicine.drug |
| Zdroj: | Brain Research. 1688:91-102 |
| ISSN: | 0006-8993 |
| DOI: | 10.1016/j.brainres.2018.03.012 |
| Popis: | 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 72 h. Exposure to systemic hypoxia (8% O2, 6 h) was followed by treatment (i.p.) with rhEPO (2500/5000 IU/kg) at 0, 24 and 48 h or FG-4497 (60/100 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. |
| Databáze: | OpenAIRE |
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