Thrombin-triggered angiogenesis in rat brains following experimental intracerebral hemorrhage.

Abstract:

OBJECT:Angiogenesis occurs after intracerebral hemorrhage (ICH). Thrombin mediates mitogenesis and survival in endothelial cells and induces angiogenesis. The present study aimed to clarify whether thrombin is involved in triggering ICH-related angiogenesis. METHODS:In the first part of the experiment, autologous blood (with or without hirudin) was injected to induce ICH. In the second part, rats received either 1 U (50 μl) thrombin or 50 μl 0.9% sterile saline. In both parts, 5-bromo-2-deoxyuridine (BrdU) was administered intraperitoneally. Brains were perfused to identify BrdU-positive/von Willebrand factor (vWF)-positive nuclei. The expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1) and Ang-2 was evaluated by immunohistochemistry and quantitative real-time reverse transcription polymerase chain reaction. RESULTS:After ICH, the number of BrdU-/vWF-positive nuclei increased until Day 14, and vessels positive for HIF-1α, VEGF, Ang-1, and Ang-2 were observed around the clot. Quantitative analysis showed that ICH upregulated expression of HIF-1α, VEGF, Ang-1, and Ang-2 notably compared with that in sham controls (p < 0.05). However, hirudin significantly inhibited these effects. After thrombin treatment, many BrdU-positive/vWF-positive nuclei and HIF-1α-, VEGF-, Ang-1- and Ang-2-positive vessels could be detected around the affected region. CONCLUSIONS:Thrombin can induce angiogenesis in rat brains and may be an important trigger for ICH-related angiogenesis.

journal_name

J Neurosurg

journal_title

Journal of neurosurgery

authors

Zhou HJ,Tang T,Cui HJ,Yang AL,Luo JK,Lin Y,Yang QD,Li XQ

doi

10.3171/2012.8.JNS112152

subject

Has Abstract

pub_date

2012-11-01 00:00:00

pages

920-8

issue

5

eissn

0022-3085

issn

1933-0693

journal_volume

117

pub_type

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