title: Loss of NB-3 aggravates cerebral ischemia by impairing neuron survival and neurite growth.
abstract: OBJECTIVE
  NB-3 is a member of the F3/contactin family of neural recognition molecules, which are crucial for cell morphogenesis and motility. NB-3 is expressed in neurons and plays an important role in axonal extension and neuronal survival. However, the role of NB-3 in cerebral ischemic injury remains unknown.
  
  
  METHODS
  Adult male wild-type and NB-3 knockout mice were subjected to ischemic injury by unilateral middle cerebral carotid artery occlusion for 3 hours, 6 hours, and 12 hours. Ischemic infarction volumes were then determined by 2, 3, 5-triphenyltetrazolium chloride staining. Neurological dysfunction analysis was also performed. Primary culture of neuronal cells from wild-type and knockout animals was also used for analysis of neuronal survival and neurite outgrowth.
  
  
  RESULTS
  NB-3 expression in the ischemic hemisphere was decreased after transient middle cerebral artery occlusion (MCAO). NB-3-knockout mice developed a 2.6-fold larger infarct volume and exhibited increased neurological deficit scores after transient middle cerebral artery occlusion compared with control mice. Substrate with NB-3 promoted neuronal survival and neurite outgrowth in vitro, whereas neurite outgrowth and neuronal survival were significantly reduced in NB-3-deficient neurons. In addition, NB-3 deficiency renders neurons more susceptible to oxygen-glucose deprivation-induced damage and NB-3 as substrate could partially through homophilic mechanisms.
  
  
  CONCLUSIONS
  These data demonstrate that NB-3 deficiency may aggravate brain damage after middle cerebral artery occlusion by impairing neuronal survival and neurite growth.
authors.affiliation: Department of Brain Protection and Plasticity, Institute of Basic Medical Sciences, No. 27 Taiping Road, Beijing 100850, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.forename: Jia
authors.initials: J
authors.lastname: Sun
authors.forename: Tong
authors.initials: T
authors.lastname: Zhao
authors.forename: Kui-Wu
authors.initials: KW
authors.lastname: Wu
authors.forename: Kazutada
authors.initials: K
authors.lastname: Watanabe
authors.forename: Zhi-Cheng
authors.initials: ZC
authors.lastname: Xiao
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Zhu
authors.forename: Ming
authors.initials: M
authors.lastname: Fan
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000235:genetics / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D002470:Cell Survival / Q000502:physiology*; D002478:Cells, Cultured; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016501:Neurites / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000378:metabolism*
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; C526283:contactin 6 protein, mouse