title: [Neuroprotection of a neotype transactivating-brain-derived neurotrophic factor fusion protein with penetrating activity of blood-brain barrier].
abstract: OBJECTIVE
  To identify the dural activities of neuroprotection and penetrating blood-brain barrier (BBB) for TAT-BDNF (transactivating-brain-derived neurotrophic factor) fusion protein to explore an alternative treatment for the injury of central nerve system (CNS).
  
  
  METHODS
  With molecular cloning techniques, a recombinant vector termed pTAT-BDNF was constructed to encode both TAT protein transduction domain and human BDNF. Purified TAT-BDNF fusion protein was generated from Escherichia coli BL21 (DE3). The injury model was established with in vitro cultured cortical neurons of neonatal rats. To observe the neuroprotective effects of TAT-BDNF fusion protein on glutamate-mediated excitotoxic insults, the contents of lactate dehydrogenase (LDH) were measured by spectrophotometry. Immunofluorescence and Hoechst 33342 analyses were used to observe the morphological changes. Immunocytochemical and Nissl stain analysis of TAT-BDNF content in CNS tissue were performed after an intravenous injection of TAT-BDNF fusion protein in normal or spinal cord injured rats.
  
  
  RESULTS
  During the study of glutamate-induced excitotoxic insults, as compared with the control group, TAT-BDNF could decrease the apoptotic ratio, reduce the leakage of LDH and enhance the survival of neurons (P < 0.05 ). As demonstrated by immunohistochemistry, TAT-BDNF fusion protein was efficiently delivered into rat brain and spinal cord tissues at 4 h post-injection. At Day 7 post-injury, Nissl stain show that the number and morphology of neurons in the TAT-BDNF group were better than those in the control group.
  
  
  CONCLUSIONS
  The synthetic neotype TAT-BDNF possess the dual biological effects of neuroprotection and penetrating BBB.
authors.affiliation: Department of Spinal Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. jianghui1992cn@yahoo.com.cn
authors.forename: Hui
authors.initials: H
authors.lastname: Jiang
authors.forename: Wei-Lin
authors.initials: WL
authors.lastname: Jin
authors.forename: Da-Di
authors.initials: DD
authors.lastname: Jin
authors.forename: Jian-Ting
authors.initials: JT
authors.lastname: Chen
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis* / Q000494:pharmacology; D015696:Gene Products, tat / Q000096:biosynthesis* / Q000494:pharmacology; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D015696:Gene Products, tat; D018696:Neuroprotective Agents