TY - JOUR
T1 - Loss of NB-3 aggravates cerebral ischemia by impairing neuron survival and neurite growth
AU - Huang, Xin
AU - Sun, Jia
AU - Zhao, Tong
AU - Wu, Kui-Wu
AU - Watanabe, Kazutada
AU - Xiao, Zhi-Cheng
AU - Zhu, Ling-Ling
AU - Fan, Ming
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
UR - http://stroke.ahajournals.org/content/42/10/2910.full.pdf+html
U2 - 10.1161/STROKEAHA.110.609560
DO - 10.1161/STROKEAHA.110.609560
M3 - Article
VL - 42
SP - 2910
EP - 2916
JO - Stroke
JF - Stroke
SN - 0039-2499
IS - 10
ER -