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Stroke. 2011 Oct;42(10):2910-6. doi: 10.1161/STROKEAHA.110.609560. Epub 2011 Aug 4.

Loss of NB-3 aggravates cerebral ischemia by impairing neuron survival and neurite growth.

Author information

1
Department of Brain Protection and Plasticity, Institute of Basic Medical Sciences, No. 27 Taiping Road, Beijing 100850, China.

Abstract

BACKGROUND AND PURPOSE:

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.

PMID:
21817151
DOI:
10.1161/STROKEAHA.110.609560
[Indexed for MEDLINE]

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