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.
Highlights
Many neuroprotective, anti-oxidative, or antiinflammatory drugs show dramatic efficacy in the experimental animal models of ischemic stroke, none of these drugs could be applied in clinical
We found that the number of lectin- and Glut-1-positive blood vessels in aged brain was the same as young adult brain (Fig. 1D and E, p>0.05), suggesting that angiogenesis in the brain was not increased during aging process
We demonstrated that: 1) aging did not affect capillary and small artery density in normal rat brain; 2) focal ischemia promoted angiogenesis in the peri-focal regions of both young and aged brain, but the number of blood vessels in aged brain was less than that in the young adult brain after ischemia; 3) aging did not affect ischemia-stimulated small artery formation
Summary
Anti-oxidative, or antiinflammatory drugs show dramatic efficacy in the experimental animal models of ischemic stroke, none of these drugs could be applied in clinical. One of the key reasons for the failure of clinical trial is that animal models of stroke are often performed in healthy young adult rather than aged animals, while stroke predominantly occurs in the aging population [1]. Using aged animal for the ischemic animal model is the critical issue to translate experimental result to the clinical application. It is well documented that focal angiogenesis is induced in young adult animals after cerebral ischemia [10, 11]. Whether ischemia induced angiogenesis occurred in aged animal brain is unclear. We investigated whether angiogenesis was induced in aged brain as did in young adult brain after focal cerebral ischemia and whether there was difference of ischemia-induced angiogenesis between young adult brain and aged brain using immunohistochemistry and synchrotron radiation microangiography
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