Rescue of cognitive function following fractionated brain irradiation in a novel preclinical glioma model

• Published in: eLife Vol. 7
• Main Authors: Feng, Xi, Liu, Sharon, Chen, David, Rosi, Susanna, Gupta, Nalin
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 13-11-2018; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: Animal behavior; Animal cognition; Animals; Brain cancer; Brain Neoplasms - complications; Brain Neoplasms - pathology; Brain Neoplasms - physiopathology; Brain Neoplasms - radiotherapy; Brain tumors; Cell Biology; Cell Proliferation - radiation effects; Cerebrospinal fluid; Cognition; Cognition - radiation effects; Cognitive ability; colony stimulating factor 1 receptor; Cranial Irradiation; Diphtheria Toxin - pharmacology; Disease Models, Animal; Dose Fractionation, Radiation; glioblastoma; Glioma; Glioma - complications; Glioma - pathology; Glioma - physiopathology; Glioma - radiotherapy; Gliomas; Male; Medical research; Memory; Memory - radiation effects; Memory Disorders - complications; Memory Disorders - physiopathology; Mice, Inbred C57BL; microglia; Microglia - pathology; Myeloid Cells - pathology; Neuroscience; Neurosciences; Novels; Patients; Quality of life; Radiation (Physics); Radiation therapy; Radiotherapy; Receptor, Macrophage Colony-Stimulating Factor - antagonists & inhibitors; Receptor, Macrophage Colony-Stimulating Factor - metabolism; recognition memory; Recognition, Psychology; Short Report; Survival; Tumors; whole-brain irradiation; United States > US; San Francisco California; California; mouse; cell biology; glioblastoma; neuroscience; colony stimulating factor 1 receptor; microglia; recognition memory; whole-brain irradiation
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.38865

More than half of long-term brain tumor survivors develop irreversible cognitive decline that severely affect their quality of life. However, there is no pre-clinical model that allows long-term assessment of cognition, and there is no treatment which ameliorates cognitive deficits in patients. Here, we report a novel glioma mouse model that offers manageable tumor growth and reliable assessment of cognitive functions in a post-treatment manner. Using this model, we found that fractionated whole-brain irradiation (fWBI), but not tumor growth, results in memory deficits. Transient inhibition of CSF-1R during fWBI prolongs survival of glioma-bearing mice and fully prevents fWBI-induced memory deficits. This result suggests that CSF-1R inhibition during radiotherapy can be explored as an approach to improve both survival and cognitive outcomes in patients who will receive fWBI. Taken together, the current study provides a proof of concept of a powerful tool to study radiation-induced cognitive deficits in glioma-bearing animals.