Nerve growth factor precursor and sortilin effects on perihematomal brain tissue and the relationship to secondary cell apoptosis

作者：Guo Shiwen; Han Yuliang^*; Bao Gang; Li Wenzhi

来源：Neural Regeneration Research, 2010, 5(1): 10-14.

DOI：10.3969/j.issn.1673-5374.2010.01.002

• intracranial hemorrhage
• cell apoptosis
• nerve growth factor precursor
• sortilin

BACKGROUND: Neuronal apoptosis in perihematomal brain tissues following intracerebral hemorrhage is strongly related to the formation of a compound signal pathway between nerve growth factor precursor (proNGF), p75NTR, and sortilin receptor. Sortilin acts as a co-receptor and molecular switch governing the p75NTR-mediated pro-apoptotic signal induced by proNGF.
OBJECTIVE: To investigate proNGF and sortilin expressions in perihematomal brain tissues following intracerebral hemorrhage, and to study the effects of proNGF and sortilin on secondary cell apoptosis.
DESIGN, TIME AND SETTING: A paired, comparison study was performed at the Laboratory of Histology and Embryology, Xi'an Jiaotong University from October 2007 to September 2008.
MATERIALS: Brain tissue samples were obtained from 15 patients with intracerebral hemorrhage, who were treated at the Department of Neurosurgery, First Affiliated Hospital, Medical College of Xi'an Jiaotong University from October 2007 to March 2008. Rabbit anti-proNGF polyclonal antibody was provided by Chemicon, USA; rabbit anti-sortilin polyclonal antibody by Abcam, UK; and TUNEL kit by Promega, USA.
METHODS: Perihematomal brain tissues selected 0.5 cm from the hemorrhage area were considered to be the hemorrhage group, while brain tissues from the middle temporal gyrus served as the control group.
MAIN OUTCOME MEASURES: Histopathological changes were detected using hematoxylin-eosin staining, cell apoptosis was determined using the TUNEL method, and proNGF and sortilin expressions were determined using immunohistochemistry.
RESULTS: Edema was clearly observed in perihematomal brain tissues, and infiltration of inflammatory cells was visible, with the presence of irregular and necrotic bodies. The apoptotic rate in the hemorrhage group was significantly greater than in the control group (P < 0.01). Moreover, sortilin expression significantly increased (P < 0.01), but proNGF expression remained unchanged (P > 0.05). Correlation analysis suggested that sortilin expression positively correlated with apoptosis (rs = 0.648, P < 0.01).
CONCLUSION: proNGF expression was stable, but sortilin expression increased in perihematomal brain tissues following intracerebral hemorrhage, suggesting that sortilin acted as a co-receptor and molecular switch to govern p75NTR-mediated cell apoptosis.

• 出版日期2010-1
• 单位西安交通大学