Protective role of COMP-Ang1 in ischemic rat brain

Hye Young Shin, Yoon Jin Lee, Hak Joo Kim, Chul Kee Park, Jong-Hoon Kim, Kyu Chang Wang, Dong Gyu Kim, Gou Young Koh, Sun Ha Paek

Research output: Contribution to journalArticle

24 Citations (Scopus)

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 b-gal (Ade-b-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.

Original languageEnglish
Pages (from-to)1052-1063
Number of pages12
JournalJournal of Neuroscience Research
Volume88
Issue number5
DOIs
Publication statusPublished - 2010 Apr 1

    Fingerprint

Keywords

  • Blood vessels
  • Cerebral ischemia
  • Gene transfer
  • Ischaemia
  • Neurogenesis
  • Neuroprotection

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

Shin, H. Y., Lee, Y. J., Kim, H. J., Park, C. K., Kim, J-H., Wang, K. C., Kim, D. G., Koh, G. Y., & Paek, S. H. (2010). Protective role of COMP-Ang1 in ischemic rat brain. Journal of Neuroscience Research, 88(5), 1052-1063. https://doi.org/10.1002/jnr.22274