Mature brain-derived neurotrophic factor and its receptor TrkB are upregulated in human glioma tissues.

There are two forms of brain-derived neurotrophic factor (BDNF), precursor of BDNF (proBDNF) and mature BDNF, which each exert opposing effects through two different transmembrane receptor signaling systems, consisting of p75 neurotrophin receptor (p75NTR) and tyrosine receptor kinase B (TrkB). Previous studies have demonstrated that proBDNF promotes cell death and inhibits the growth and migration of C6 glioma cells through p75NTR in vitro, while mature BDNF has opposite effects on C6 glioma cells. It is hypothesized that mature BDNF is essential in the development of malignancy in gliomas. However, histological data obtained in previous studies were unable distinguish mature BDNF from proBDNF due to the lack of specific antibodies. The present study investigated the expression of mature BDNF using a specific sheep monoclonal anti-mature BDNF antibody in 42 human glioma tissues of different grades and 10 control tissues. The correlation between mature BDNF and TrkB was analyzed. Mature BDNF expression was significantly increased in high-grade gliomas, and was positively correlated with the malignancy of the tumor and TrkB receptor expression. The present data have demonstrated that increased levels of mature BDNF contribute markedly to the development of malignancy of human gliomas through the primary BDNF receptor TrkB.

ProBDNF and its receptors are upregulated in glioma and inhibit the growth of glioma cells in vitro.

BACKGROUND: High-grade glioma is incurable, with a short survival time and poor prognosis. The increased expression of p75 neurotrophin receptor (NTR) is a characteristic of high-grade glioma, but the potential significance of increased p75NTR in this tumor is not fully understood. Since p75NTR is the receptor for the precursor of brain-derived neurotrophic factor (proBDNF), it is suggested that proBDNF may have an impact on glioma. METHODS: In this study we investigated the expression of proBDNF and its receptors p75NTR and sortilin in 52 cases of human glioma and 13 cases of controls by immunochemistry, quantitative real-time PCR, and Western blot methods. Using C6 glioma cells as a model, we investigated the roles of proBDNF on C6 glioma cell differentiation, growth, apoptosis, and migration in vitro. RESULTS: We found that the expression levels of proBDNF, p75NTR, and sortilin were significantly increased in high-grade glioma and were positively correlated with the malignancy of the tumor. We also observed that tumors expressed proBDNF, p75NTR, and sortilin in the same cells with different subcellular distributions, suggesting an autocrine or paracrine loop. The ratio of proBDNF to mature BDNF was decreased in high-grade glioma tissues and was negatively correlated with tumor grade. Using C6 glioma cells as a model, we found that proBDNF increased apoptosis and differentiation and decreased cell growth and migration in vitro via p75NTR. CONCLUSIONS: Our data indicate that proBDNF and its receptors are upregulated in high-grade glioma and might play an inhibitory effect on glioma.

[Establishment of maca mulatta model of resuscitation after selective cerebral ultra-deep hypothermic blood flow occlusion].

OBJECTIVE: To study the feasibility of resuscitation after selective cerebral ultra-deep hypothermia and blood flow occlusion. METHODS: Ten 4-10 year-old maca mulattas were divided into 3 groups: four-vessel occlusion group, two-vessel occlusion group and identical temperature perfusion group. MRI were examinated before and after operation, the vital signs and the hemodynamical parameters were observed during the experiment, neurological deficient evaluation was performed after operation. RESULTS: In all of the ten monkeys, the hemodynamical parameters of two-vessel occulation were steady during the operation, and all of them lived after filling 60 minutes. MRI were normal after operation, and the function of neurological deficient scale was normal. The others of identical temperature perfusion group and four-vessel occlusion group were not resuscitation after filling 60 minutes and died. CONCLUSION: Monkey could resuscitate from selective cerebral ultra-deep hypothermia and blood flow occlusion of bilateral common carotid artery in 60 minutes.

[Effects on neuronal ultrastructure and nervous system of monkey after selective cerebral profound hypothermia and blood flow occlusion].

OBJECTIVE: To study the effects of deep hypothermia on the neuronal ultrastructure and nervous system of monkey after selective cerebral profound hypothermia and blood flow occlusion. METHODS: Brain-local extracorporeal circulation was established by right internal carotid artery deep hypothermic perfusion and homolateral external jugular vein backflow, brain blood flow was recovered from circulatory arrest 60 - 80 minutes late and monkey came back naturally. RESULTS: In all 7 monkeys, 5 were succeeded in being build up the models except for 2 because of technic problems, and 4 of them lived up for ever. The function of nervous system grade, essential organ and neuronal ultrastructure were normal. CONCLUSION: Selective cerebral profound hypothermia can increase the ability of brain to endure hypovolemia and hypoxidosis and prolong the time of blood flow occlusion.