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Protective role of COMP-Ang1 in ischemic rat brain

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Authors
Shim, Hye Young; Lee, Yoon Jin; Kim, Hak Joo; Park, Chul-Kee; Kim, Jong Hoon; Wang, Kyu Chang; Kim, Dong Gyu; Koh, Gou Young; Paek, Sun Ha
Issue Date
2009-11
Publisher
Wiley-Blackwell
Citation
J Neurosci Res. 88:1052–1063
Keywords
blood vesselscerebral ischemiaGene transferNeuroprotectionischaemiaNeurogenesis
Abstract
In cerebral ischemia, the induction of angiogenesis may represent a natural defense mechanism that enables the hypoxic brain to avoid progression into infarction. Angiopoietin-1 (Ang1) is known to produce non-leaky and stable blood vessel formation mainly by the Tie2 receptor. Therefore, we envisioned that the application of cartilage oligomeric matrix protein-Ang1 (COMP-Ang1), a soluble, stable, and potent form of Ang1, would promote angiogenesis and provide a protective effect following unilateral middle cerebral artery occlusion (MCAO) in rats. To this end, we employed a 2-hour-MCAO model, and treated rats with adenovirus encoding COMP-Ang1 (Ade-COMP-Ang1) or control virus encoding β-gal (Ade-β-gal). Time course magnetic resonance images (MRIs) revealed significantly reduced infarct volume in the rats treated with Ade-COMP-Ang1 with an improvement of post-ischemic neurological deficits compared with rats treated with Ade-β-gal. Moreover, compared to the rats treated with Ade-β-gal, the rats treated with Ade-COMP-Ang1 showed an increase in blood vessels, especially in the border zone adjacent to the infarction, increased number of endogenous neuronal progenitor cells in the ischemic brain, and decreased number of TUNEL-positive cells. Taken together, COMP-Ang1 reduced infarct volume and consequently attenuated post-ischemic neurological deficits through enhanced angiogenesis and increased viable cell mass of neuronal cells.
ISSN
1097-4547
Language
English
URI
https://hdl.handle.net/10371/74229
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College of Medicine/School of Medicine (의과대학/대학원)Neurosurgery (신경외과학전공)Journal Papers (저널논문_신경외과학전공)
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