Potassium and glutamate transport is impaired in scar-forming tumor-associated astrocytes

Publication date: Available online 9 December 2019Source: Neurochemistry InternationalAuthor(s): Susan C. Campbell, Carmen Muñoz-Ballester, Lata Chaunsali, William A. Mills, Jennifer H. Yang, Harald Sontheimer, Stefanie RobelAbstractUnprovoked recurrent seizures are a serious comorbidity affecting most patients who suffer from glioma, a primary brain tumor composed of malignant glial cells. Cellular mechanisms contributing to the development of recurrent spontaneous seizures include the release of the excitatory neurotransmitter glutamate from glioma into extracellular space. Under physiological conditions, astrocytes express two high affinity glutamate transporters, Glt-1 and Glast, which are responsible for the removal of excess extracellular glutamate. In the context of neurological disease or brain injury, astrocytes become reactive which can negatively affect neuronal function, causing hyperexcitability and/or death. Using electrophysiology, immunohistochemistry, fluorescent in situ hybridization, and Western blot analysis in different orthotopic xenograft and allograft models of human and mouse gliomas, we find that peritumoral astrocytes exhibit astrocyte scar formation characterized by proliferation, cellular hypertrophy, process elongation, and increased GFAP and pSTAT3. Overall, peritumoral reactive astrocytes show a significant reduction in glutamate and potassium uptake, as well as decreased glutamine synthetase activity. A subset of peritumoral astrocytes ...
Source: Neurochemistry International - Category: Neuroscience Source Type: research

Related Links:

Conditions:   Glioma;   Glioma, Malignant;   Glioblastoma;   Glioblastoma Multiforme;   Glioblastoma Multiforme of Brain;   GBM;   Brain Cancer Intervention:   Procedure: Laparoscopically harvested omental free flap Sponsor:   Northwell Health Recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
ConclusionsThe CNS penetration observed was encouraging enough to move ribociclib forward with preclinical efficacy studies in models of pediatric brain tumors.
Source: Cancer Chemotherapy and Pharmacology - Category: Cancer & Oncology Source Type: research
CONCLUSIONS: The significant survival benefit of intra-cavity chemotherapy demonstrates clinical applicability of PLGA/PEG paste-mediated delivery of temozolomide and etoposide adjuvant to radiotherapy. PLGA/PEG paste offers a future platform for combination delivery of molecular targeted compounds. PMID: 31113843 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
Qiancheng Deng1, Yangyang Luo1,2, Christopher Chang3, Haijing Wu1, Yan Ding4* and Rong Xiao1* 1Hunan Key Laboratory of Medical Epigenetics, Department of Dermatology, The Second Xiangya Hospital, Central South University, Changsha, China 2Department of Dermatology, Hunan Children's Hospital, Changsha, China 3Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, Davis, CA, United States 4Department of Dermatology, Hainan Provincial Dermatology Disease Hospital, Haikou, China Autoimmune diseases are usually complex and multifactorial, characterized by aberrant produc...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusion The expression of the components of the PTN-MK-RPTPβ/ζ axis in immune cells and in inflammatory diseases suggests important roles for this axis in inflammation. Pleiotrophin has been recently identified as a limiting factor of metainflammation, a chronic pathological state that contributes to neuroinflammation and neurodegeneration. Pleiotrophin also seems to potentiate acute neuroinflammation independently of the inflammatory stimulus while MK seems to play different -even opposite- roles in acute neuroinflammation depending on the stimulus. Which are the functions of MK and PTN in chronic neuroinfla...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Pediatric patients with brain tumors have limited treatment options and poor long-term survival. CDK4/6 bound with Cyclin D regulates cell proliferation by phosphorylating retinoblastoma protein (Rb) and releasing E2F, a positive regulator of the G1/S transition. Ribociclib, a CDK4/6 inhibitor is under clinical evaluation for treatment of pediatric malignancies. We evaluated its CNS penetration in two pediatric brain tumor models (diffuse intrinsic pontine glioma [DIPG] and Group 3 medulloblastoma [G3MB]) and in normal mouse brain using cerebral microdialysis. A plasma pharmacokinetic study of 100 mg/kg orally-ad...
Source: Neuro-Oncology - Category: Cancer & Oncology Authors: Tags: PEDIATRIC TUMORS - PRECLINICAL STUDIES (NON-IMMUNOLOGICAL) Source Type: research
More News: Bone Graft | Brain | Brain Cancers | Brain Tumor | Cancer & Oncology | Glioma | Neurology | Neuroscience | Potassium