title: Neuronal regeneration and protection by collagen-binding BDNF in the rat middle cerebral artery occlusion model.
abstract: 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.
authors.affiliation: Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.
authors.forename: Jian
authors.initials: J
authors.lastname: Guan
authors.forename: Weimin
authors.initials: W
authors.lastname: Tong
authors.forename: Wenyong
authors.initials: W
authors.lastname: Ding
authors.forename: Shiwei
authors.initials: S
authors.lastname: Du
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Xiao
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Han
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Zhu
authors.forename: Xinjie
authors.initials: X
authors.lastname: Bao
authors.forename: Ximin
authors.initials: X
authors.lastname: Shi
authors.forename: Chenxi
authors.initials: C
authors.lastname: Wu
authors.forename: Jiani
authors.initials: J
authors.lastname: Cao
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.forename: Wenbin
authors.initials: W
authors.lastname: Ma
authors.forename: Guilin
authors.initials: G
authors.lastname: Li
authors.forename: Yong
authors.initials: Y
authors.lastname: Yao
authors.forename: Jun
authors.initials: J
authors.lastname: Gao
authors.forename: Junji
authors.initials: J
authors.lastname: Wei
authors.forename: Jianwu
authors.initials: J
authors.lastname: Dai
authors.forename: Renzhi
authors.initials: R
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000150:complications / Q000000981:diagnostic imaging / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism* / Q000494:pharmacology; D003094:Collagen / Q000378:metabolism*; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000000981:diagnostic imaging / Q000473:pathology*; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009416:Nerve Regeneration / Q000187:drug effects; D055495:Neurogenesis / Q000187:drug effects; D010477:Perfusion; D049268:Positron-Emission Tomography; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D003094:Collagen; D005947:Glucose