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Neuronal regeneration and protection by collagen-binding BDNF in the rat middle cerebral artery occlusion model

Guan, Jian, Tong, Weimin, Ding, Wenyong, Du, Shiwei, Xiao, Zhifeng, Han, Qianqian, Zhu, Zhaohui, Bao, Xinjie, Shi, Ximin, Wu, Chenxi, Cao, Jiani, Yang, Yi, Ma, Wenbin, Li, Guilin, Yao, Yong, Gao, Jun, Wei, Junji, Dai, Jianwu, Wang, Renzhi
Biomaterials 2012 v.33 no.5 pp. 1386-1395
angiogenesis, apoptosis, cell proliferation, collagen, ependyma, metabolism, models, rats, stroke, therapeutics
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.