Metabolism, Compartmentation, Transport and Production of Acetate in the Cortical Brain Tissue Slice

2012 ◽  
Vol 37 (11) ◽  
pp. 2541-2553 ◽  
Author(s):  
Caroline Rae ◽  
Aurélie D. Fekete ◽  
Mohammed A. Kashem ◽  
Fatima A. Nasrallah ◽  
Stefan Bröer
Keyword(s):  
2004 ◽  
Vol 100 (6) ◽  
pp. 1049-1059 ◽  
Author(s):  
Christopher D. Duntsch ◽  
Qihong Zhou ◽  
Himangi R. Jayakar ◽  
James D. Weimar ◽  
Jon H. Robertson ◽  
...  

Object. The purpose of this study was to evaluate both replication-competent and replication-restricted recombinant vesicular stomatitis virus (VSV) vectors as therapeutic agents for high-grade gliomas by using an organotypic brain tissue slice—glioma coculture system. Methods. The coculture system involved growing different brain structures together to allow neurons from these tissues to develop synaptic connections similar to those found in vivo. Rat C6 or human U87 glioma cells were then introduced into the culture to evaluate VSV as an oncolytic therapy. The authors found that recombinant wild-type VSV (rVSV-wt) rapidly eliminated C6 glioma cells from the coculture, but also caused significant damage to neurons, as measured by a loss of microtubule-associated protein 2 immunoreactivity and a failure in electrophysiological responses from neurons in the tissue slice. Nonetheless, pretreatment with interferon beta (IFNβ) virtually eliminated VSV infection in healthy tissues without impeding any oncolytic effects on tumor cells. Despite the protective effects of the IFNβ pretreatment, the tissue slices still showed signs of cytopathology when exposed to rVSV-wt. In contrast, pretreatment with IFNβ and inoculation with a replication-restricted vector with its glycoprotein gene deleted (rVSV-ΔG) effectively destroyed rat C6 and human U87 glioma cells in the coculture, without causing detectable damage to the neuronal integrity and electrophysiological properties of the healthy tissue in the culture. Conclusions. Data in this study provide in vitro proof-of-principle that rVSV-ΔG is an effective oncolytic agent that has minimal toxic side effects to neurons compared with rVSV-wt and therefore should be considered for development as an adjuvant to surgery in the treatment of glioma.


Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2707
Author(s):  
Vasile Sidorcenco ◽  
Luisa Krahnen ◽  
Marion Schulz ◽  
Janina Remy ◽  
Donat Kögel ◽  
...  

Glioblastomas (GBMs) are the most malignant brain tumors and are essentially incurable even after extensive surgery, radiotherapy, and chemotherapy, mainly because of extensive infiltration of tumor cells into the adjacent normal tissue. Thus, the evaluation of novel drugs in malignant glioma treatment requires sophisticated ex vivo models that approach the authentic interplay between tumor and host environment while avoiding extensive in vivo studies in animals. This paper describes the standardized setup of an organotypic brain tissue slice tandem-culture system, comprising of normal brain tissue from adult mice and tumor tissue from human glioblastoma xenografts, and explore its utility for assessing inhibitory effects of test drugs. The microscopic analysis of vertical sections of the slice tandem-cultures allows for the simultaneous assessment of (i) the invasive potential of single cells or cell aggregates and (ii) the space occupying growth of the bulk tumor mass, both contributing to malignant tumor progression. The comparison of tissue slice co-cultures with spheroids vs. tissue slice tandem-cultures using tumor xenograft slices demonstrates advantages of the xenograft tandem approach. The direct and facile application of test drugs is shown to exert inhibitory effects on bulk tumor growth and/or tumor cell invasion, and allows their precise quantitation. In conclusion, we describe a straightforward ex vivo system mimicking the in vivo situation of the tumor mass and the normal brain in GBM patients. It reduces animal studies and allows for the direct and reproducible application of test drugs and the precise quantitation of their effects on the bulk tumor mass and on the tumor’s invasive properties.


2021 ◽  
Author(s):  
Yuxin Ma ◽  
Yunyao Cai ◽  
Zeyu Wang ◽  
Mingzhu Sun ◽  
Xin Zhao

2006 ◽  
Vol 37 (03) ◽  
Author(s):  
R Husain ◽  
HS Fink ◽  
K Lang ◽  
B Merkle ◽  
R Bauer ◽  
...  
Keyword(s):  

2014 ◽  
Vol 37 (2) ◽  
pp. 85 ◽  
Author(s):  
Ata Topcuoglu ◽  
Mustafa Albayrak ◽  
Hayriye Erman ◽  
Huriye Balci ◽  
Mesut Karakus ◽  
...  

Purpose: The purpose of this study was to analyze the effects of estrogen deficiency and hormone replacement therapy (HRT) on fibrinolytic activity in a rat mode of surgically-induced menopause. Methods: Twelve-week-old, sexually mature female Sprague-Dawley rats, each weighing 200–250 g, were randomly divided into four groups: (1) sham-operated group, (2) ovariectomy group, (3) ovariectomy group followed by oral administration of daily 17β-estradiol (0.02 mg/kg/day) (E2) + norethisterone acetate (0.01 mg/kg/day), and (4) ovariectomy group followed by oral administration of daily 17β-estradiol (0.01 mg/kg/day) + drospirenone (0.02 mg/kg/day). Tissue plasminogen activator (tPA) antigen, plasminogen activator inhibitor-1 (PAI-1) antigen, and PAI-1/tPA levels were measured as markers of fibrinolysis in plasma and liver and brain tissue. Results: Compared with sham-operated rats, ovariectomized rats showed higher levels of fibrinolytic activity; however, the increased fibrinolytic activity in plasma and liver tissue was significantly reduced by HRT regimens. No change was observed in the levels of fibrinolytic activity in brain tissue. Conclusions: HRT showed beneficial effects by decreasing fibrinolytic activity related to surgically-induced menopause. Short-term HRT treatment was associated with a shift in the procoagulant-anticoagulant balance toward a procoagulant state.


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