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 language | English |
|---|---|
| Pages (from-to) | 1052-1063 |
| Number of pages | 12 |
| Journal | Journal of Neuroscience Research |
| Volume | 88 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 2010 Apr 1 |
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Keywords
- Blood vessels
- Cerebral ischemia
- Gene transfer
- Ischaemia
- Neurogenesis
- Neuroprotection
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience
Cite this
Protective role of COMP-Ang1 in ischemic rat brain. / Shin, 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.
In: Journal of Neuroscience Research, Vol. 88, No. 5, 01.04.2010, p. 1052-1063.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Protective role of COMP-Ang1 in ischemic rat brain
AU - Shin, Hye Young
AU - Lee, Yoon Jin
AU - Kim, Hak Joo
AU - Park, Chul Kee
AU - Kim, Jong-Hoon
AU - Wang, Kyu Chang
AU - Kim, Dong Gyu
AU - Koh, Gou Young
AU - Paek, Sun Ha
PY - 2010/4/1
Y1 - 2010/4/1
N2 - 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.
AB - 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.
KW - Blood vessels
KW - Cerebral ischemia
KW - Gene transfer
KW - Ischaemia
KW - Neurogenesis
KW - Neuroprotection
UR - http://www.scopus.com/inward/record.url?scp=77950111925&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77950111925&partnerID=8YFLogxK
U2 - 10.1002/jnr.22274
DO - 10.1002/jnr.22274
M3 - Article
C2 - 19885826
AN - SCOPUS:77950111925
VL - 88
SP - 1052
EP - 1063
JO - Journal of Neuroscience Research
JF - Journal of Neuroscience Research
SN - 0360-4012
IS - 5
ER -