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Aging and disease    2016, Vol. 7 Issue (4) : 326-335     DOI: 10.14336/AD.2015.1125
Original Article |
Ischemia-induced Angiogenesis is Attenuated in Aged Rats
Tang Yaohui1,2, Wang Liuqing3, Wang Jixian5, Lin Xiaojie1, Wang Yongting1, Jin Kunlin3,4,*, Yang Guo-Yuan1,5,*
1Neuroscience and Neuroengineering Center, Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China
2Department of Orthopaedic surgery, School of medicine, Stanford University, CA 94305, USA
3Department of Neurology, the First Affiliated Hospital, Wenzhou Medical University, Zhejiang, 325000, China
4Department of Pharmacology and Neuroscience, University of North Texas Health Science Center at Fort Worth, TX 76203, USA
5Shanghai Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai 200030, China
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Abstract  

To study whether focal angiogenesis is induced in aged rodents after permanent distal middle cerebral artery occlusion (MCAO), young adult (3-month-old) and aged (24-month-old) Fisher 344 rats underwent MCAO and sacrificed up to two months after MCAO. Immunohistochemistry and synchrotron radiation microangiography were performed to examine the number of newly formed blood vessels in both young adult and aged rats post-ischemia. We found that the number of capillaries and small arteries in aged brain was the same as young adult brain. In addition, we found that after MCAO, the number of blood vessels in the peri-infarct region of ipsilateral hemisphere in aged ischemic rats was significantly increased compared to the aged sham rats (p<0.05). We also confirmed that ischemia-induced focal angiogenesis occurred in young adult rat brain while the blood vessel density in young adult ischemic brain was significantly higher than that in the aged ischemic brain (p<0.05). Our data suggests that focal angiogenesis in aged rat brain can be induced in response to ischemic brain injury, and that aging impedes brain repairing and remodeling after ischemic stroke, possible due to the limited response of angiogenesis.

Keywords aging      angiogenesis      focal cerebral ischemia      rat      brain     
Corresponding Authors: Jin Kunlin,Yang Guo-Yuan   
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These authors contributed equally to this study.

Issue Date: 01 August 2016
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Tang Yaohui
Wang Liuqing
Wang Jixian
Lin Xiaojie
Wang Yongting
Jin Kunlin
Yang Guo-Yuan
Cite this article:   
Tang Yaohui,Wang Liuqing,Wang Jixian, et al. Ischemia-induced Angiogenesis is Attenuated in Aged Rats[J]. Aging and disease, 2016, 7(4): 326-335.
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http://www.aginganddisease.org/EN/10.14336/AD.2015.1125     OR     http://www.aginganddisease.org/EN/Y2016/V7/I4/326
Figure 1.  The number of blood vessels in normal young adult and aged rat brain. Photomicrographs showed lectin (A) and Glut-1 (B) staining in the cortex and striatum of the normal young adult (left panel) and aged (right panel) rat brain. Lectin-positive cells was well merged with Glut-1 staining (C), indicating these are endothelial cells and blood vessels. Scale bar=20 µm. The quantitation of the blood vessels in the normal young and aged rats was assessed with either lectin (D) or Glut-1 (E) staining. Data were presented as mean±SD. n.s. p>0.05, the number of blood vessels in normal young vs. that in normal aged rats. N=6 per group.
Figure 2.  The number of blood vessels in aged rat brain after focal cerebral ischemia. Photomicrographs showed lectin and Glut-1 staining in aged normal (A and B, left panel) and aged ischemic brain (right panel). Scale bar=20 µm. Bar graph showed that the quantitative number of blood vessels in ipsilateral hemisphere of ischemic and normal rat brain from lectin (C) and Glut-1 (D) staining. Data were presented as mean±SD. *, p<0.05, the number of blood vessels in aged normal rats vs. aged ischemic rats. N=6 per group.
Figure 3.  The number of blood vessels in young adult and aged rat brain after focal ischemia. Photomicrographs showed lectin and Glut-1 staining in the ipsilateral hemisphere in young adult ischemic (A and B, left panel) and aged ischemic brain (right panel). Scale bar =20 µm. Bar graph showed that the quantitative number of blood vessels in ipsilateral hemisphere of young adult and aged rat brain from lectin (C) and Glut-1 (D) staining. Data were presented as mean±SD. *, p<0.05, the number of microvessels of ipsilateral hemisphere in young adult ischemic vs. that in aged ischemic rats. N=6 per group.
Figure 4.  Quantification of small arteries in young adult and aged rat brain. Photomicrographs showed that SMA-positive small arteries in normal aged and ischemic aged rat brains (A). Scale bar=20 µm. Bar graph showed that semi-quantitative number of small arteries in normal young adult and normal aged brain (B), young sham-operated and young ischemic rat brain (C), and aged sham-operated and aged ischemic rats (D). Data were presented as mean±SD. **, p<0.01, the number of small arteries in normal young vs. that in ischemic young brain; ##, p<0.01, the number of small arteries in normal aged vs. that in ischemic aged brain. N=6 per group.
Figure 5.  Live SRA of blood vessels in young and aged rat brain after focal ischemia. A representative SRA image of young sham rat (A). MCA, ICA, ACA and PA indicate middle cerebral artery, internal cerebral artery, anterior cerebral artery and penetrating artery, respectively. B. Photomicrographs showed the perfusion of the MCA territory in normal young rat (a), normal aged rat (b), young ischemic rat (c) and aged ischemic rat (d). a1, b1, c1 and d1 show magnified view of the boxed region. More functional branches of MCA were detected in the young ischemic rats. Bar=500 µm.
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