Issue release date: 12.11.2024
2China Three Gorges University, Institute of Neurology, Yichang, Hubei, China
3China Three Gorges University, The First College of Clinical Medical Sciences, Department of Neurology, Yichang, Hubei, China
4China Three Gorges University, The First College of Clinical Medical Sciences, Department of Intensive Care Unit, Yichang, Hubei, China
5Central South University, Institute of Integrative Medicine, Xiangya Hospital, Changsha, Hunan, China DOI : 10.5137/1019-5149.JTN.18901-16.1 AIM: Angiogenesis occurs after intracerebral hemorrhage (ICH). Hypoxia-inducible factor-1α (HIF-1?) is a critical regulator of angiogenesis. However, its role in the central nervous system remains controversial. 2-Methoxyestradiol (2ME2), a natural metabolite of estrogen, is known to inhibit HIF-1α. In the present study, we investigated the effect of 2ME2 in a rat model of ICH-induced angiogenesis.
MATERIAL and METHODS: Sprague-Dawley male rats (n=50) were randomly divided into 5 groups: Sham operated group; ICH; ICH+2ME2; and ICH+Vehicle groups. ICH model was induced by stereotactic injection of collagenase type VII into the right globus pallidus. 2ME2 or vehicle (10% dimethyl sulfoxide) was administered intraperitoneally 10 min after ICH. Angiogenesis and expression of HIF-1α was evaluated by immunohistochemistry, quantitative real time-reverse transcription polymerase chain reaction and western blot, respectively.
RESULTS: Proliferating cell nuclear antigen (PCNA)-labeled nuclei were detected in cerebral endothelial cells (ECs) around the hematoma. The labeling peaked at 14 days post-ICH. HIF-1α-immunoreactive microvessels with dilated outline were detected in the perihematomal tissues. The vessels extended into the clot from the surrounding tissues from day 7 onwards. HIF-1α protein levels increased, while no change was observed in HIF-1α mRNA expression after ICH. 2ME2 decreased the PCNA-labeled nuclei in cerebral ECs and down-regulated the expression of HIF-1α protein as well, while it had little effect on the mRNA expression of HIF-1?.
CONCLUSION: HIF-1α inhibitor, 2ME2, inhibited post-ICH angiogenesis by suppressing HIF-1α expression, thus exerting detrimental effects in ICH.
Keywords : 2-methoxyestradiol, Intracerebral hemorrhage, Angiogenesis, Hypoxia-inducible factor-1α