Differential regulation of angiogenesis in the developing mouse brain in response to exogenous activation of the hypoxia-inducible transcription factor system.

摘要: Abstract 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 HIF suggested as neuroprotective option, however, studies its effects on vascular development are limited. We analyzed influence prolyl-4-hydroxylase inhibitor (PHI), FG-4497, and erythropoietin (rhEPO) post-hypoxic angiogenesis (angiogenic growth factors, vessel structures) in mouse (P7) assessed after regeneration period 72 h. Exposure systemic hypoxia (8% O2, 6 h) was followed treatment (i.p.) with rhEPO (2500/5000 IU/kg) at 0, 24 48 h or FG-4497 (60/100 mg/kg) compared controls. In response cortical hippocampal area branching were significantly increased This associated elevated ANGPT-2 well decreased ANGPT-1 TIE-2 mRNA levels. rhEPO, mildly but also levels comparison conclusion, present data demonstrate differential regulation angiopoietin/TIE-2 system PHI pointing potential functional consequences for development.