title: The promotion of cerebral ischemia recovery in rats by laminin-binding BDNF.
abstract: Brain-derived neurotrophic factor (BDNF) has been shown to have therapeutic effects on cerebral ischemia. However, the delivery approach limits its application. Laminin is a rich extra cellular matrix in the central nervous system, and is highly expressed in the ischemic region after cerebral ischemia. We reported here by fusing with laminin-binding domain (LBD) to BDNF to construct laminin-binding BDNF (LBD-BDNF). LBD-BDNF could target accumulated laminin in the ischemic region and exert targeting therapy of injured neurons after ischemia. We examined the laminin-binding ability and neurotrophic bioactivity of LBD-BDNF in vitro, and assessed its targeting therapy using a rat permanent middle cerebral artery occlusion (MCAO) model in vivo. It was found that LBD-BDNF could specifically bind to laminin and maintain BDNF activity both in vitro and in vivo. LBD-BDNF treatment attenuated neural-degeneration after MCAO, and also resulted in a reduction of infarct volume that is associated with a parallel improvement in neurological functional outcome and neurogenesis in the dentate gyrus of hippocamp.
authors.affiliation: Key laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100080, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Han
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.forename: Hua
authors.initials: H
authors.lastname: Feng
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Xiao
authors.forename: Bing
authors.initials: B
authors.lastname: Chen
authors.forename: Yannan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Jingchun
authors.initials: J
authors.lastname: Huang
authors.forename: Jianwu
authors.initials: J
authors.lastname: Dai
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D005109:Extracellular Matrix / Q000737:chemistry; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery; D007797:Laminin / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D009410:Nerve Degeneration / Q000473:pathology / Q000517:prevention & control; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D007797:Laminin; D011993:Recombinant Fusion Proteins