Journal
BIOMATERIALS
Volume 33, Issue 5, Pages 1386-1395Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2011.10.073
Keywords
Collagen; Brain-derived neurotrophic factor; Drug delivery; Nerve regeneration; Wound healing
Funding
- National Natural Science Foundation of China [30930032, 81100869]
- National High Technology Research Project [2006AA02A115, 2011AA020112]
- Chinese Academy of Sciences [XDA01030401]
- National Basic Research Program of China (973 Program) [2011CB965000]
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It has been well confirmed that brain-derived neurotrophic factor (BDNF) has therapeutic effects following stroke. However, it is difficult to be maintained at a sufficient concentration of BDNF in the infarcted hemisphere. We have shown in our previous work that BDNF fused with a collagen-binding domain (CBD-BDNF) could specifically bind to collagen. The ventricular ependyma of the brain is rich in collagen. Therefore, we have speculated that in the infarcted hemisphere, CBD-BDNF will bind to the collagen of the ventricular ependyma and stimulate the cell proliferation in the subventricular zone (SVZ). Using a rat middle cerebral artery occlusion model (MCAO), we injected CBD-BDNF into the lateral ventricle of MCAO rats. The results demonstrated that CBD-BDNF was retained at high levels in the infarcted hemisphere, promoted neural regeneration and angiogenesis, reduced cell loss, decreased apoptosis, and improved functional recovery. In addition, brain perfusion and metabolism, as evaluated by SPECT and PET, were improved in the CBD-BDNF treated group. (C) 2011 Elsevier Ltd. All rights reserved.
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